Research

 

 

Aboytes Torres, R., Y. Liang, and Schulze T. I. (1996). Analisis de la expresion in vitro del gene de la hemaglutinina del virus de la influenza aviar via un marcador citoquimico y microscopia confocal de rayo laser. [Analysis of the in vitro expression of the Ha gene from an avian influenza virus, by using cytochemistry and confocal microscopy]. In: Reunion Nacional de Investigacion Pecuaria, Cuernavaca, Morelos [Mexico], p. 49.

            Abstract: El estudio fue disenado para desarrollar un nuevo sistema de deteccion de la expresion in vitro de la molecula de HA, utilizando como marcador citoquimico una fetoproteina y un sistema de deteccion mediante microscopia confocal. El gene de la HA del virus de la influenza aviar A/DW/WI/1938/80 (H1N1), fue insertado en el vector pREP10 y clonado en E. coli DH5 alfa. Monoestratos de celulas MDBK y MDCK con indices de confluencia de entre 30 y 50% fueron transformados mediante la tecnica de transfeccion con liposomas. La seleccion de celulas transformadas se llevo a cabo con el tratamiento de los cultivos con higromicina como marcador de seleccion (600 micro l/ml en medio DME completocon 10% v/v suero bovino fetal) por un periodo de 3 a 4 semanas. Los cultivos celulares transformados en forma estable fueron crecidos en cubreobjetos y fijados en paraformaldehido (3.7% en PBS pH 7.2). La expresion temporal o constitutiva del gene de la HA en celulas mamiferas transformadas fue monitoreada con las tecnicas estandarizadas de IFI (con anticuerpos mono y policlonales), hemoadsorcion y hemoaglutinacion. La nueva tecnica alternativa desarrollada se baso en la reaccion de acoplamiento mediada por la alta afinidad entre el sitio de reconocimiento del recptor, situado en los polipeptidos de la molecula de HA y el acido sialico de la fetoproteina bovina (0.2% acido acetilneuroamidico) conjugada con oro coloidal (10nm). Los ensayos incluyeron los analisis de la reaccion a nivel de citoplasma y de superficie. Para este efecto se utilizaron monoestratos permeabilizados con el detergente Tween 20 (0.05%) y monoestratos no permeabilizadas. Los controles incluyeron celulas infectadas con virus homologos y heterologos (WSN). Se concluye que la nueva tecnica descrita, ofrece una alta especificidad y sensibilidad analitica en la deteccion de HA expresada in vitro a la vez que es rapida y sencilla. Ademas, el potencial de esta tecnica puede ser extrapolado en ensayos utilizando microscopia optica.

            Descriptors: avian influenza virus, cytochemistry, cell structure, confocal microscopy, influenza virus, viruses.

Air, G.M., L.R. Ritchie, W.G. Laver, and P.M. Colman (1985). Gene and protein sequence of an influenza neuraminidase with hemagglutinin activity. Virology 145(1): 117-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  An influenza virus neuraminidase (NA) of the N9 subtype also has hemagglutinin (HA) activity (W. G. Laver, P. M. Colman, R. G. Webster, V. S. Hinshaw, and G. M. Air (1984), Virology 137, 314-323). To determine sequence relationships between this NA and other known NA and HA subtype sequences, and as a necessary step toward a complete structure determination, we have cloned a full-length copy of the coding sequence of the N9 NA of influenza virus A/tern/Australia/G70C/75 into the plasmid pUC9 using SalI linkers. The gene was sequenced by directed subcloning into the single-stranded phage vectors M13mp19 and M13mp18 and use of the dideoxy procedure. Most of the NA sequence was also obtained by direct protein sequencing of tryptic peptides. The N9 NA has 43 and 44% homology when compared to N1 or N2 sequences, respectively. There is no significant homology to any known HA sequence, or to the HN protein of the paramyxovirus SV5. Like the other NA molecules, the N9 NA is anchored in the membrane by an N-terminal hydrophobic region, from which biologically active heads can be released by pronase.

            Descriptors:  genes viral, hemagglutinins viral, influenza A virus avian enzymology, influenza A virus enzymology, neuraminidase genetics, amino acid sequence, base sequence, cloning, molecular, influenza A virus avian genetics, avian immunology, influenza A virus genetics, influenza A virus immunology.

Akhmatullina, N.B. and K.G. Mustafin (1982). Biologicheski aktivnye ribonukleoproteidy kletok, zarazhennykh virusom chumy ptits. [Biologically active ribonucleoproteins of cells infected with fowl plague virus]. Voprosy Virusologii (1): 29-32.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The results of studies of physico-chemical and biological properties of virus-specific ribonucleoproteins (RNP) in influenza infection are presented. Particular attention is given to the infectious properties of RNP. The earliest infectivity was found to be associated with RNP structures sedimenting from nuclear extract in a zone of 30-40S.

            Descriptors:  nucleoproteins pharmacology, ribonucleoproteins pharmacology, cell nucleus microbiology, chemistry, physical, chick embryo, cytoplasm microbiology, influenza A virus avian pathogenicity, ribonucleoproteins isolation and purification, species specificity, time factors, virus cultivation.

Akkina, R.K. (1990). Antigenic reactivity and electrophoretic migrational heterogeneity of the three polymerase proteins of type A human and animal influenza viruses. Archives of Virology 111(3-4): 187-97.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Antigenic reactivity of the three polymerase proteins PB1, PB2, and PA of type A influenza viruses of animal and human origin were analysed by radioimmunoprecipitation using monospecific antisera. Each of the polymerase monospecific antisera made against the polymerase proteins of the human A/WSN/33 (H1N1) influenza virus reacted efficiently with the homologous proteins of all the known thirteen HA subtype viruses of avian influenza virus, three subtypes of human influenza virus, swine and equine influenza viruses. This broad reactivity of each of the antisera indicated that the polymerase proteins are antigenically related among the type A influenza viruses and therefore can be considered as type specific antigens similar to the other viral internal proteins nucleoprotein (NP) and matrix protein (M). No electrophoretic migrational heterogeneity was found among the PB2 proteins of different subtype viruses, whereas PB1 protein exhibited minor variation. However, PA protein from among various viral subtypes showed considerable heterogeneity. Each of the polymerase antisera also immunoprecipitated additional antigenically related polypeptides with distinct electrophoretic mobilities from cells infected with each of the influenza viral subtypes.

            Descriptors:  DNA directed RNA polymerases immunology, influenza A virus human enzymology, influenza A virus enzymology, viral proteins immunology, antigens, viral immunology, human immunology, influenza A virus immunology, precipitin tests.

Alexander, D.J., M.S. Collins, and M. Parkinson. (1981). Plaque-forming ability in MDCK cells and structure of the haemagglutinin of influenza A viruses which differ in virulence for chickens. In: Proceedings of the First International Symposium on Avian Influenza, Beltsville, Maryland, USA, p. 148-156.

            NAL Call Number: aSF995.6.I6I5 1981a

            Descriptors: avian influenza A virus, virulence, hemagglutinin, cells, chickens.

Alexander, D.J., G. Parsons, and R.J. Manvell (1986). Experimental assessment of the pathogenicity of eight avian influenza A viruses of H5 subtype for chickens, turkeys, ducks and quail. Avian Pathology 15(4): 647-662.  ISSN: 0307-9457.

            NAL Call Number:  SF995.A1A9

            Descriptors:  avian influenza virus, chickens, turkeys,  ducks, quails, chickens, immune response, disease transmission, clinical signs, mortality.

Alexander, D.J., G.F. Wood, M.S. Collins, J. Banks, and R.J. Manvell (1996). Recent work on the pathogenicity of avian influenza viruses and the pathogenicity and antigenicity of Newcastle disease virus. Proceedings of the Western Poultry Diseases Conference 45: 1-4.

            NAL Call Number:  SF995.W4

            Descriptors:  Newcastle disease virus, avian influenza virus, influenza virus, orthomyxoviridae, paramyxoviridae, viruses.

Almeida, J.D. and C.M. Brand (1975). A morphological study of the internal component of influenza virus.  Journal of General Virology 27(3): 313-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Rapid treatment of influenza virus directly on the microscope grid with non-ionic detergent had allowed better visualization of the internal component. Many micrographs show that this ribonucleoprotein (RNP) is present as a continuous stand of 6 nm diam. arranged in the form of a double coil or helix. In spite of the minimal treatment to which the virus was subjected most helices still showed signs of degradation. The findings that we have obtained lead us to suggest that the RNP component of influenza virus must be very sensitive to both chemical and physical manipulations, any of which could cause it to fracture from one continuous strand into several pieces, although such breakages could possibly occur at specific points along its length.

            Descriptors:  orthomyxoviridae ultrastructure, RNA, viral, viral proteins, chick embryo, cyprinidae, influenza A virus avian ultrastructure, microscopy, electron, phosphotungstic acid, recombination, genetic, surface active agents, tissue culture.

Almeida, J.D. and A.P. Waterson (1967). Some observations on the envelope of an influenza virus. Journal of General Microbiology 46(1): 107-10.  ISSN: 0022-1287.

            NAL Call Number:  448.3 J823

            Descriptors:  influenza A virus avian, lipoproteins analysis, microscopy, electron, viral proteins analysis.

Almond, J.W. (1977). A single gene determines the host range of influenza virus. Nature 270(5638): 617-8.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Descriptors:  genes viral, influenza A virus avian genetics, virus replication, cell line, DNA directed RNA polymerases genetics, DNA directed RNA polymerases metabolism, avian physiology, RNA viral genetics, viral proteins genetics, viral proteins physiology.

Almond, J.W. and R.D. Barry (1979). Genetic recombination between two strains of fowl plague virus: construction of genetic maps. Virology 92(2): 407-15.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, influenza A virus avian genetics, RNA viral genetics, electrophoresis, polyacrylamide gel, avian analysis, viral analysis, recombination, genetic, viral proteins analysis, viral proteins biosynthesis.

Almond, J.W. and V. Felsenreich (1982). Phosphorylation of the nucleoprotein of an avian influenza virus. Journal of General Virology 60(Pt. 2): 295-305.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  High resolution polyacrylamide gel electrophoresis (PAGE) of chick embryo fibroblast cells infected with the avian influenza virus FPV-Rostock revealed two distinct polypeptides migrating in the region of the nucleoprotein (NP). One-dimensional fingerprinting of these polypeptides showed that they were both nucleoprotein, and [32P]orthophosphate labelling revealed that they differed with respect to their state of phosphorylation. Pulse-chase studies using [35S]methionine indicated that phosphorylation of a certain proportion of NP occurs rapidly after synthesis and is associated with transport to the nucleus. Nucleoprotein which remained in the cytoplasm was predominantly non-phosphorylated. Both the phosphorylated and the non-phosphorylated types of NP were found in ribonucleoprotein complexes (RNPs) of different densities isolated on renografin gradients, but RNPs isolated from the nucleus contained much more phosphorylated NP than those from the cytoplasm. The kinase responsible for nucleoprotein phosphorylation appears to be influenced by temperature of incubation of the infected cells.

            Descriptors:  influenza A virus avian metabolism, nucleoproteins metabolism, viral proteins metabolism, cell line, cell nucleus analysis, cell nucleus metabolism, chick embryo, cytoplasm analysis, fibroblasts, phosphorylation, protein kinases metabolism, ribonucleoproteins analysis, temperature.

Almond, J.W., D. McGeoch, and R.D. Barry (1977). Method for assigning temperature-sensitive mutations of influenza viruses to individual segments of the genome. Virology 81(1): 62-73.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes, influenza A virus avian growth and development, mutation, chick embryo, avian analysis, avian radiation effects, peptides analysis, RNA viral analysis, recombination, genetic, temperature, tissue culture, ultraviolet rays, viral proteins analysis, virus replication.

Almond, J.W., D. McGeoch, and R.D. Barry (1979). Temperature-sensitive mutants of fowl plague virus: isolation and genetic characterization. Virology 92(2): 416-27.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, influenza A virus avian genetics, recombination, genetic, avian analysis, mutation, temperature, viral proteins analysis, viral proteins biosynthesis.

Altmuller, A., W.M. Fitch, and C. Scholtissek (1989). Biological and genetic evolution of the nucleoprotein gene of human influenza A viruses. Journal of General Virology 70(Pt.  8): 2111-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  There is a significant difference in the ability of human influenza A virus H1N1 strains isolated up to 1977 and those isolated later to rescue temperature-sensitive mutants of fowl plague virus with a defect in the nucleoprotein (NP) gene. Therefore the NP genes of five human H1N1 and H3N2 influenza A virus strains, isolated between 1950 and 1978, have been sequenced. By comparison with previous and more recent isolates, an evolutionary pathway has been established. Three amino acid replacements were found which might be responsible for the functional difference between the USSR (1977) and the Brazil (1978) strains. The California (H1N1) strain isolated in 1978 had acquired by reassortment the NP gene of a human H3N2 virus circulating at about 1977 as had been previously suggested by investigations involving RNase fingerprint or hybridization techniques.

            Descriptors:  evolution, genes viral, influenza A virus human genetics, nucleoproteins genetics, viral core proteins, viral proteins genetics, amino acid sequence, base sequence, chick embryo, chickens, influenza A virus avian genetics, molecular sequence data, mutation, sequence homology, nucleic acid.

Altmuller, A., M. Kunerl, K. Muller, V.S. Hinshaw, W.M. Fitch, and C. Scholtissek (1992). Genetic relatedness of the nucleoprotein (NP) of recent swine, turkey, and human influenza A virus (H1N1) isolates. Virus Research 22(1): 79-87.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The sequences of nucleoprotein (NP) genes of recent human and turkey isolates of influenza A viruses, which serologically could be correlated to contemporary swine viruses, were determined. These sequences were closely related to the NPs of these swine viruses and they formed a separate branch on the phylogenetic tree. While the early swine virus from 1931 resembled the avian strains in consensus amino acids of the NP and in its ability to rescue NP ts mutants of fowl plague virus in chicken embryo cells, the later strains on that branch were different: at 15 positions they have their own amino acids and they rescued the NP ts mutants only poorly. Of the NPs of the human New Jersey/76 isolates analysed, one clustered with the recent H1N1 swine viruses of the U.S.A., the other one with contemporary human strains. Since the NP is one of the main determinants of species specificity it is concluded that, although the H1N1 swine isolates from the U.S.A. form their own branch in the phylogenetic tree, they can be transmitted to humans and turkeys, but they do not spread further in these populations and so far have not contributed to human pandemics. It is not very likely that they will do so in future, since its branch in the phylogenetic tree develops further away from the human and avian branch.

            Descriptors:  influenza A virus avian genetics, human genetics, porcine genetics, nucleoproteins genetics, fowl plague microbiology, influenza microbiology, phylogeny, sequence homology, nucleic acid, turkeys.

Anisimova, E., Y. Ghendon, and S. Markushin (1980). Ultrastructural changes in cells induced by temperature-sensitive mutants of fowl plague virus at permissive and non-permissive temperature. Journal of General Virology 47(1): 11-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Ultrastructural changes developing in chick embryo fibroblast cultures infected with a wild-type strain of fowl plague virus (FPV) or one of six FPV temperature-sensitive (ts) mutants belonging to different complementation groups were studied. Cells infected with wild-type FPV and incubated at optimal (36 degrees C) or nonpermissive temperature (42 degrees C) displayed changes similar to those described for orthomyxoviruses. The same patterns of changes were observed at 36 degrees C in cells infected with ts mutants belonging to five of the complementation groups. Mutant ts 303, possessing mutation-altered haemagglutinin, induced at 36 degrees C the formation of virions carrying a considerably reduced number of spikes on their surfaces. At 42 degrees C, cells infected with ts mutant 131, with a defective primary transcription stage, showed no morphological changes and no formation of electron-dense inclusions. Cells infected with ts mutants with defective secondary transcription or replication displayed nuclear inclusions but no formation of filamentous cytoplasmic structures or virions. Mutant ts 5 with defective late morphogenesis induced formation of considerably enhanced numbers of nuclear inclusions.

            Descriptors:  cell transformation, viral, influenza A virus avian, cell nucleus ultrastructure, cultured cells, chick embryo, fibroblasts ultrastructure, inclusion bodies, viral ultrastructure, microscopy, electron, mutation, temperature, virion ultrastructure.

Anonymous (1998). From the Centers for Disease Control and Prevention. Isolation of avian influenza A(H5N1) viruses from humans--Hong Kong, May-December 1997. JAMA the Journal of the American Medical Association 279(4): 263-4.  ISSN: 0098-7484.

            NAL Call Number:  448.9 Am37

            Descriptors:  influenza epidemiology, influenza A virus avian isolation and purification, adolescent, adult, child, child, preschool, Hong Kong epidemiology, influenza virology, middle aged.

Anonymous (1998). From the Centers for Disease Control and Prevention. Update: isolation of avian influenza A(H5N1) viruses from humans--Hong Kong, 1997-1998. JAMA the Journal of the American Medical Association 279(5): 347-8.  ISSN: 0098-7484.

            NAL Call Number:  448.9 Am37

            Descriptors:  influenza epidemiology, influenza virology, influenza A virus avian isolation and purification, Hong Kong epidemiology, seroepidemiologic studies.

Anschutz, W., C. Scholtissek, and P. Rott (1972). Genetic relationship between different influenza strains. Medical Microbiology and Immunology 158(1): 26-31.  ISSN: 0300-8584.

            Descriptors:  influenza strains, influenza A virus, genetic relationships, Hong Kong.

Armstrong, S.J. and R.D. Barry (1974). The topography of RNA synthesis in cells infected with fowl plague virus. Journal of General Virology 24(3): 535-47.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian metabolism, RNA viral biosynthesis, autoradiography, cell nucleus enzymology, cell nucleus metabolism,  cultured cells, chick embryo, cytoplasm enzymology, DNA directed RNA polymerases metabolism, deoxyadenosines pharmacology, fibroblasts, avian enzymology, avian growth and development, mycotoxins pharmacology, Newcastle disease virus growth and development, Newcastle disease virus metabolism, time factors, tritium, uracil nucleotides metabolism, uridine metabolism,  virus replication.

Armstrong, S.J., M.C. Outlaw, and N.J. Dimmock ( 1990). Morphological studies of the neutralization of influenza virus by IgM. Journal of General Virology 71(Pt. 10):  2313-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Quantitative relationships between neutralization, aggregation and attachment to monolayers of chick embryo fibroblast (CEF) cells have been studied using a constant amount of influenza A/fowl plague virus/Rostock/34 (H7N1) and varying amounts of purified mouse polyclonal IgM directed against the haemagglutinin, the major viral neutralization antigen. There are two major types of interaction. (i) At low concentrations of IgM there is aggregation of virus, but no neutralization provided that the aggregates are dispersed by vortexing and dilution. Maximum aggregation occurs at less than seven molecules of IgM per virion and the IgM is probably bound in the 'staple' or 'crab' conformation at these concentrations. (ii) At higher concentrations there is neutralization and this coincides with inhibition of attachment of virus to CEF cells. Neutralization of 50% infectivity requires about 35 molecules of IgM per virion. The maximum neutralization observed was only 87%. Quantitative data and electron microscopy observations suggest that molecules of IgM at the higher concentrations adopt a planar stance approximately perpendicular to the viral surface. It appears that IgM neutralizes fowl plague virus in vitro primarily by interfering with its attachment to cells; the fraction of neutralized virus that does attach is known not be internalized.

            Descriptors:  antibodies, viral immunology, immunoglobulin M immunology, influenza A virus avian immunology, antigen antibody complex, immunohistochemistry, avian ultrastructure, microscopy, electron, neutralization tests.

Asadullaev, T.A. and A.G. Bukrinskaia (1976). Kharakteristika RNK, vydelennoi iz iadernogo RNK-sinteziruiushchego kompleksa virusa grippa. [Characteristics of RNA isolated from the nuclear RNA-synthesizing complex of influenza virus]. Voprosy Virusologii (6): 656-9.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  When Ehrlich ascitic carcinoma cells infected with classical fowl plague virus and treated with actinomycin D were pulse labeled for 10 min with 3H-uridine, it was mainly incorporated into nucleoplasm structures sedimenting in sucrose gradients at 120S. At 2-hr exposure of the infected cells to 3H-uridine radioactivity was found in nucleoplasm in the area of 65S and in the cytoplasm in 30-40S zone. The analysis of RNA isolated from these structures gave the following results. The RNA isolated from 120S structures sedimented in two zones of sucrose gradient: 11S and 16-23S. The 11S RNA was resistant to RNA-ase, while 16-23S RNA was sensitive to RNA-ase. A similar (16-23S) RNA was isolated from virus-specific structures 65S and 30-40S.

            Descriptors:  influenza A virus avian, RNA viral biosynthesis, viral isolation and purification, virus replication, carcinoma, Ehrlich tumor analysis, carcinoma, Ehrlich tumor microbiology, catalysis, cell nucleus metabolism, centrifugation, density gradient, ribonucleases, transcription, genetic, uridine metabolism.

Asadullaev, T.A., A.K. Gitel'man, and A.G. Bukrinskaia (1975). Abortivnaia infektsiia miksovirusov v kletkakh astsitnoi kartsinomy Erlikha. Analiz virusspetsificheskikh struktur v astsitnoi zhidkosti. [Abortive myxovirus infection of Ehrlich ascites carcinoma cells. Analysis of virus-specific structures in the ascitic fluid]. Voprosy Virusologii (3): 278-82.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  In the course of classical fowl plague virus reproduction in Ehrlich ascites carcinoma cells both hemagglutinins and S-antigen accumulate and titers of the infectious activity increase. However virus reproduction does not terminate in formation of virus, and subviral structures are found in the liquid fraction of the infected cells. Analysis of these structures has shown them to have a sedimentation coefficient of 350-370S and buovant density 1.29 g/ml. The rapidly sedimenting structure has complement-fixing hemagglutinating activity but bow infectivity.

            Descriptors:  carcinoma, Ehrlich tumor microbiology, influenza A virus avian growth and development, virus replication, amino acids, antigens, viral analysis, carcinoma, Ehrlich tumor analysis, centrifugation, density gradient, complement fixation tests, hemagglutinins viral analysis, methionine, sulfur radioisotopes, tritium.

Assadullaeff, T., A.K. Gitelman, and A.G. Bukrinskaya (1975). Influenza virus RNA-synthesizing complex in the nucleoplasm of infected cells. Journal of General Virology 29(1): 137-42.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  An RNA-synthesizing complex was found in the nucleoplasm of fowl plague virus-infected chicken fibroblast and Ehrlich tumour cells. The complex sedimented at 120 S and banded in caesium chloride at 1-39 to 1-41 g/ml. It contained an influenza nucleocapsid protein as a major protein constituent. The complex functioned late in infection, and RNA synthesis in it was resistant to actinomycin D, the properties expected of influenza virus replicative complex.

            Descriptors:  cell nucleus metabolism, influenza A virus avian metabolism, RNA viral biosynthesis, carcinoma, Ehrlich tumor, chick embryo, dactinomycin pharmacology, fibroblasts, avian growth and development, mice, tissue culture, viral proteins biosynthesis, virus replication.

Astapovich, L.G., G.A. Ivanova, and S.B. Logginov (1968). Elektronnomikroskopicheskoe izuchenie shtammov virusa klassicheskoi chumy ptits. [An electron microscopic study of strains of the virus of classic fowl plague]. Veterinariia 45(9): 24-6.  ISSN: 0042-4846.

            NAL Call Number:  41.8 V6426

            Descriptors:  influenza A virus avian cytology, chick embryo, microscopy, electron.

Atsev, S., I. Gagov, and I. Mikhailov (1981). Vurkhu tsitologichite razlichiia v kletuchni kulturi, zarazeni s virusa na klasicheskata chuma po ptitsite i gripen virus tip A. [Cytological differences in cell cultures infected with classical fowl plague virus and influenza virus type A]. Acta Microbiologica Bulgarica 9: 79-86.  ISSN: 0204-8809.

            NAL Call Number:  QR1.A37

            Descriptors:  influenza A virus avian pathogenicity, cattle, cytopathogenic effect, viral, time factors, virus cultivation, virus replication.

Austin, F.J., Y. Kawaoka, and R.G. Webster (1990). Molecular analysis of the haemagglutinin gene of an avian H1N1 influenza virus. Journal of General Virology 71(Pt. 10): 2471-4.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  This study presents the first nucleotide sequence and deduced primary amino acid sequence of a subtype H1 haemagglutinin from the avian influenza virus A/duck/Alberta/35/76 (H1N1). The molecule is structurally, antigenically and molecularly similar to H1 haemagglutinins of human viruses but sequence homology differences indicate that there has not been a recent transfer of haemagglutinin genetic information between them.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, amino acid sequence, base sequence, genes, structural, viral, avian immunology, molecular sequence data.

Austin, F.J. and R.G. Webster (1986). Antigenic mapping of an avian H1 influenza virus haemagglutinin and interrelationships of H1 viruses from humans, pigs and birds. Journal of General Virology 67(Pt. 6): 983-92.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Monoclonal antibodies to the haemagglutinin (HA) of the avian H1 influenza virus A/duck/Alberta/35/76 were used to construct an operational antigenic map of the HA molecule and to study the interrelationships of H1 viruses from different hosts. Haemagglutination inhibition tests between the monoclonal antibodies and variants selected by them provided evidence of four antigenic regions which overlap to varying degrees. Avian H1 influenza viruses displayed a spectrum of reactivities to the monoclonal antibody panel. Representatives of the epidemic strains of human H1 influenza viruses and early swine influenza viruses showed little or no reactivity with the monoclonal antibodies but swine influenza-like viruses isolated from pigs and humans in the last decade reacted with 11 of 17 antibodies. The antigenic similarity of these viruses to many avian isolates suggests that there has been a transfer of HA genetic information between mammalian and avian H1 influenza viruses.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, antibodies, monoclonal diagnostic use, epitopes, human immunology, porcine immunology, species specificity.

Avery, R.J. (1975). Abortive infection of L cells by influenza virus: absence of virion RNA synthesis. Journal of Virology 16(2): 311-4.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza virus multiplies productively in chick cells and abortively in L cells. The infecting influenza virus RNA genomes are less stable in infected L cells than in infected chick cells. However, transcription of the virus genome in L cells, while reduced in rate, is not decreased in extent. There is no detectable synthesis of virion RNA in L cells, and this is the most likely cause of the abortive infection.

            Descriptors:  influenza A virus avian metabolism, L cells cell line, RNA viral biosynthesis, chick embryo, fibroblasts, avian growth and development, mice, nucleic acid hybridization, phosphorus radioisotopes, tissue culture, transcription, genetic, virus replication.

Avery, R.J. (1974). The subcellular localization of virus-specific RNA in influenza virus-infected cells. Journal of General Virology 24(1): 77-88.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian growth and development, RNA viral analysis, virus replication, base sequence, cell nucleus analysis, chick embryo, cytoplasm analysis, nucleic acid hybridization, RNA, ribosomal analysis, ribonucleases, time factors, tritium, uridine.

Aymard, M., A.R. Douglas, M. Fontaine, J.M. Gourreau, C. Kaiser, J. Million, and J.J. Skehel (1985). Antigenic characterization of influenza A (H1N1) viruses recently isolated from pigs and turkeys in France. Bulletin of the World Health Organization 63(3): 537-42.  ISSN: 0042-9686.

            NAL Call Number:  449.9 W892B

            Descriptors:  antigens, viral analysis, influenza A virus avian immunology, porcine immunology, immunology, swine microbiology, turkeys microbiology, France, avian isolation and purification, porcine isolation and purification.

Baez, M., R. Taussig, J.J. Zazra, J.F. Young, P. Palese, A. Reisfeld, and A.M. Skalka (1980). Complete nucleotide sequence of the influenza A/PR/8/34 virus NS gene and comparison with the NS genes of the A/Udorn/72 and A/FPV/Rostock/34 strains. Nucleic Acids Research 8(23): 5845-58.  ISSN: 0305-1048.

            NAL Call Number:  QD341.A2N8

            Abstract:  The nucleotide sequence of the NS gene of the human influenza virus A/PR/8/34 was determined and found to be the same length (890 nucleotides) as the NS gene of another human influenza virus A/Udorn/72 and of the avian isolate A/FPV/Rostock/34. Comparison of the sequences of the NS genes of the two human influenza viruses shows an 8.9% difference whereas the NS gene of the avian isolate differs by only 8% from that of the human strain A/PR/8/34. The extensive sequence similarity among these three genes does not support the notion of species specific homology groups among NS genes of avian and human influenza virus strains. The primary sequence of the A/PR/8/34 NS gene is consistent with the findings that the influenza virus NS gene may code for two overlapping polypeptides. In addition, an open reading frame potentially coding for a polypeptide 167 amino acids in length was found in the negative strand RNA of the A/PR/8/34 virus NS gene.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, RNA viral genetics, amino acid sequence, base sequence, cloning, molecular, peptides genetics, species specificity.

Baigent, S.J., R.C. Bethell, and J.W. McCauley ( 1999). Genetic analysis reveals that both haemagglutinin and neuraminidase determine the sensitivity of naturally occurring avian influenza viruses to zanamivir in vitro. Virology 263(2): 323-38.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  antiviral agents pharmacology, genes viral physiology, hemagglutinins viral metabolism, influenza A virus avian drug effects, neuraminidase antagonists and inhibitors, neuraminidase metabolism, sialic acids pharmacology, amino acid sequence, base sequence, cultured cells, chick embryo, chickens blood, chickens virology, dogs, erythrocytes virology, genes viral genetics, glycosylation,  hemagglutination, viral drug effects, hemagglutinins viral genetics, avian enzymology, avian genetics, avian physiology, inhibitory concentration 50, lactose analogs and derivatives, lactose metabolism, molecular sequence data, mutation genetics, neuraminidase chemistry, neuraminidase genetics, reassortant viruses drug effects, reassortant viruses enzymology, reassortant viruses genetics, reassortant viruses physiology, sialic acids metabolism, substrate specificity, virus replication, drug effects.

Baigent, S.J. and J.W. McCauley (2001). Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture. Virus Research 79(1-2): 177-85.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The influence on virus replication in culture of the presence and location of glycosylation sites on the haemagglutinin (HA) glycoprotein of avian influenza viruses and differences in length of the stalk region of their neuraminidase (NA) glycoprotein was examined using reassortant viruses. Plaque size was measured in the presence or absence of bacterial neuraminidase (CPNA) and/or an influenza virus NA inhibitor, zanamivir, to assess the relative contribution of the NA to replication efficiency in tissue culture. The following conclusions were drawn, (1) HA lacking glycosylation at 158 gives inefficient growth when combined with short-stalked NAs, and efficient growth when combined with long-stalked NAs. (2) Glycosylation at 158 of HA makes the virus less dependent on NA for release from its receptors. (3) HA with glycosylation at 158 gives efficient growth when combined with short-stalked NAs but, when combined with long-stalked NAs, growth is very efficient and excess NA activity is disadvantageous. (4) HA having glycosylation at 158 combined with short-stalked NAs, or HA lacking glycosylation at 158 combined with long-stalked NAs may represent optimal combinations. The results reinforce the importance of a balance of HA and NA activity for efficient virus exit from, and entry into cells.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian growth and development, neuraminidase metabolism, antiviral agents pharmacology, chick embryo, C lostridium perfringens enzymology, enzyme inhibitors pharmacology, glycosylation, hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus genetics, avian drug effects, avian genetics, avian physiology, neuraminidase antagonists and inhibitors, plaque assay, protein structure, tertiary, sialic acids pharmacology.

Baker, A.T., J.N. Varghese, W.G. Laver, G.M. Air, and P.M. Colman (1987). Three-dimensional structure of neuraminidase of subtype N9 from an avian influenza virus. Proteins 2(2): 111-7.  ISSN: 0887-3585.

            NAL Call Number:  QP551.P698

            Abstract:  Neuraminidases from different subtypes of influenza virus are characterized by the absence of serological cross-reactivity and an amino acid sequence homology of approximately 50%. The three-dimensional structure of the neuraminidase antigen of subtype N9 from an avian influenza virus (A/tern/Australia/G70c/75) has been determined by X-ray crystallography and shown to be folded similarly to neuraminidase of subtype N2 isolated from a human influenza virus. This result demonstrates that absence of immunological cross-reactivity is no measure of dissimilarity of polypeptide chain folding. Small differences in the way in which the subunits are organized around the molecular fourfold axis are observed. Insertions and deletions with respect to subtype N2 neuraminidase occur in four regions, only one of which is located within the major antigenic determinants around the enzyme active site.

            Descriptors:  influenza A virus avian enzymology, neuraminidase immunology, neuraminidase metabolism, amino acid sequence, antigens, viral, binding sites, avian classification, models, molecular, molecular sequence data, n acetylneuraminic acid, protein conformation, sialic acids metabolism.

Banbura, M.W., Y. Kawaoka, T.L. Thomas, and R.G. Webster (1991). Reassortants with equine 1 (H7N7) influenza virus hemagglutinin in an avian influenza virus genetic background are pathogenic in chickens. Virology 184(1): 469-471.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Reassortants possessing the hemagglutinin (HA) gene from A/Equine/London/1416/73 (H7N7) [Eq/Lond) and five or more genes from A/Chicken/Pennsylvania/1370/83 (H5N2) [Ck/Penn] were lethal in chickens. This result demonstrates that horses can maintain influenza viruses whose HAs are capable of promoting virulence. Thus, reassortment of equine and avian influenza virus genes could generate viruses that might be lethal in domestic poultry.

            Descriptors:  fowls, horses, avian influenza virus, equine influenza virus, hemagglutinins, genes, amino acids, virulence, pathogenicity, mortality, molecular sequence data, EMBL m58657, GENBANK m58657.

Bankowski, R.A. (1975). Interferon and its role in poultry health. American Journal of Veterinary Research 36(4): 494-497.  ISSN: 0002-9645.

            NAL Call Number:  41.8 Am3A

            Descriptors:  interferon, viral diseases, poultry.

Banks, J., E.C. Speidel, J.W. McCauley, and D.J. Alexander (2000). Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses. Archives of Virology 145(5): 1047-58.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A 945 nucleotide region (bases 76-1020) of the HA1 part of the HA gene was obtained for 31 influenza viruses of H7 subtype isolated primarily from Europe, Asia and Australia over the last 20 years. These were analysed phylogenetically and compared with sequences of the same region from 23 H7 subtype viruses available in Genbank. The overall results showed two geographically distinct lineages of North American and Eurasian viruses with major sublineages of Australian, historical European and equine viruses. Genetically related sublineages and clades within these major groups appeared to reflect geographical and temporal parameters rather than being defined by host avian species. Viruses of high and low virulence shared the same phylogenetic branches, supporting the theory that virulent viruses are not maintained as a separate entity in waterfowl.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian classification, avian genetics, amino acid sequence, fowl plague virology, genes viral, avian isolation and purification, phylogeny, poultry, sequence homology, amino acid.

Banks, J., E.S. Speidel, E. Moore, L. Plowright, A. Piccirillo, I. Capua, P. Cordioli, A. Fioretti, and D.J. Alexander (2001). Changes in the haemagglutinin and the neuraminidase genes prior to the emergence of highly pathogenic H7N1 avian influenza viruses in Italy. Archives of Virology 146(5): 963-73.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Outbreaks of avian influenza due to an H7N1 virus of low pathogenicity occurred in domestic poultry in northern Italy from March 1999 until December 1999 when a highly pathogenic avian influenza (HPAI) virus emerged. Nucleotide sequences were determined for the HA1 and the stalk region of the neuraminidase (NA) for viruses from the outbreaks. The HPAI viruses have an unusual multibasic haemagglutinin (HA) cleavage site motif, PEIPKGSRVRRGLF. Phylogenetic analysis showed that the HPAI viruses arose from low pathogenicity viruses and that they are most closely related to a wild bird isolate, A/teal/Taiwan/98. Additional glycosylation sites were present at amino acid position 149 of the HA for two separate lineages, and at position 123 for all HPAI and some low pathogenicity viruses. Other viruses had no additional glycosylation sites. All viruses examined from the Italian outbreaks had a 22 amino acid deletion in the NA stalk that is not present in the N1 genes of the wild bird viruses examined. We conclude that the Italian HPAI viruses arose from low pathogenicity strains, and that a deletion in the NA stalk followed by the acquisition of additional glycosylation near the receptor binding site of HA1 may be an adaptation of H7 viruses to a new host species i.e. domestic poultry.

            Descriptors:  fowl plague virology, hemagglutinins viral genetics, influenza A virus avian genetics, neuraminidase genetics, poultry diseases virology, amino acid motifs, amino acid sequence, birds virology, chickens virology, disease outbreaks, evolution, molecular, fowl plague epidemiology, genes, structural, viral, glycosylation, influenza A virus avian isolation and purification, influenza A virus avian pathogenicity, Italy epidemiology, molecular sequence data, phylogeny, poultry diseases epidemiology, protein processing, post translational, sequence deletion, sequence homology, turkeys virology, virulence genetics.

Bano, S., K. Naeem, and S.A. Malik (2003). Evaluation of pathogenic potential of avian influenza virus serotype H9N2 in chickens. Avian Diseases 47(Special Issue): 817-822.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Recently seven isolates of avian influenza virus (AIV) serotype H9N2 recovered from an outbreak of AI were analyzed on the basis of their biological and molecular characteristics. All the isolates belonged to the low-pathogenicity group of AIV. To further evaluate their pathogenic potential in association with other organisms, an isolate was inoculated experimentally in chickens using different routes and subsequently challenged with infectious bronchitis virus, Ornithobacterium rhinotracheale or Escherichia coli. The virus isolation and seromonitoring data revealed a significant role of Escherichia coli in aggravating the clinical condition of the birds earlier infected with AIV (H9N2). The AIV-antigen was detected in lung, trachea, kidney, and cloacal bursa among the infected birds, using immunofluorescent antibody technique. In another experiment, chickens that were immunosuppressed chemically showed high mortality when challenged with AIV H9N2. The results indicated that this low pathogenicity AIV (H9N2) isolate could produce severe infection depending on the type of secondary opportunistic pathogens present under field conditions. This may explain the severity of infection with the present H9N2 outbreak in the field. A prolonged antibacterial therapy in flocks infected with AIV H9N2 and use of oil-based vaccine at an early age in new flocks has helped to control this infection and the disease.

            Descriptors:  epidemiology, infection, avian influenza, infectious disease, respiratory system disease, viral disease, immunofluorescence, immunologic techniques, laboratory techniques, viral isolation, disease outbreak, secondary opportunistic pathogens, seromonitoring data.

Barich, N.L., E.A. Evteeva, and N.V. Kaverin (1992). Svoistva vnutrikletochnykh virus-spetsificheskikh ribonukleoproteidov, soderzhashchikh negativnye i pozitivnye RNK virusagrippa A. [Properties of intracellular virus-specific ribonucleoproteins containing negative and positive hepatitis A virus RNA]. Molekuliarnaia Genetika, Mikrobiologiia i Virusologiia (9-10): 15-9.  ISSN: 0208-0613.

            NAL Call Number:  QH506.M65F2

            Abstract:  The characteristics of the intracellular virus-specific nucleocapsids containing either a negative or a positive RNA strand were studied. The immunosorption of nucleocapsids by the monoclonal antibodies against the three epitopes of NP protein failed to reveal any antigenic difference between the negative strand or positive strand-containing nucleocapsids. On the other hand, the sensitivity of virus-specific RNA in the nucleocapsids to digestion by the pancreatic ribonuclease proved to be lower for the positive strand-containing nucleocapsids.

            Descriptors:  influenza A virus avian genetics, RNA viral chemistry, ribonucleoproteins analysis, chick embryo, epitopes immunology, ribonucleoproteins immunology.

Barry, R.D. and P. Davies (1970). The effects of UK2054 on the multiplication of influenza viruses. Journal of Hygiene 68(1): 151-8.  ISSN: 0022-1724.

            NAL Call Number:  449.8 J82

            Descriptors:  isoquinolines pharmacology, orthomyxoviridae drug effects, chick embryo, fetal membranes, hemagglutination tests, immune sera, influenza A virus avian drug effects, orthomyxoviridae growth and development, virus inhibitors pharmacology.

Basak, S. and R.W. Compans (1983). Studies on the role of glycosylation in the functions and antigenic properties of influenza virus glycoproteins. Virology 128(1): 77-91.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The biological and antigenic roles of glycosylation were investigated in the influenza hemagglutinin (HA) glycoprotein using the glycosylation inhibitor tunicamycin (TM). Under conditions where only the nonglycosylated form of HA was detected by immunoprecipitation and gel electrophoresis, the migration of glycoproteins to the cell surface was observed by immunofluorescence using either monospecific or monoclonal antibody to the HA polypeptide. Analysis of the surface fluorescence in TM-treated infected cells by a fluorescence-activated cell sorter (FACS) showed that all cells exhibited fluorescence in the complete absence of glycosylation. The relative amount of HA antigen on cell surfaces was found to be reduced by only 30-40% in TM-treated cells, and this reflected a similar reduction in intracellular synthesis. Electron microscopic studies using ferritin labeling also demonstrated that the nonglycosylated HA glycoprotein was present in significant amounts on surfaces of infected cells. Virions with nonglycosylated glycoproteins were purified, and were found to have an approximate 30-fold decrease in both hemagglutinin and neuraminidase specific activities. The possible role of oligosaccharides in antigenic variation among various H1N1 strains was investigated. Immunoprecipitation reactions involving five different monoclonal antibodies and five antigenic variants of A/USSR/90/77 revealed no major antigenic differences between the glycosylated and nonglycosylated forms of HA.

            Descriptors:  cell membrane analysis, hemagglutinins viral analysis, influenza A virus avian analysis, human analysis, antibodies, monoclonal immunology, antibodies, viral immunology, epitopes immunology, hemagglutination, viral, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, neuraminidase metabolism, tunicamycin pharmacology.

Bashiruddin, J.B., A.R. Gould, and H.A. Westbury (1992). Molecular pathotyping of two avian influenza viruses isolated during the Victoria 1976 outbreak. Australian Veterinary Journal 69(6): 140-2.  ISSN: 0005-0423.

            NAL Call Number:  41.8 Au72

            Descriptors:  chickens, disease outbreaks veterinary, fowl plague microbiology, influenza A virus avian classification, RNA viral analysis, amino acid sequence, base sequence, DNA, viral chemistry, fowl plague epidemiology, hemagglutinins viral chemistry, hemagglutinins viral genetics, influenza A virus avian genetics, molecular sequence data, polymerase chain reaction, viral chemistry, Victoria epidemiology.

Baum, L.G. and J.C. Paulson (1990). Sialyloligosaccharides of the respiratory epithelium in the selection of human influenza virus receptor specificity. Acta Histochemica. Supplement Band 40: 35-8.  ISSN: 0567-7556.

            NAL Call Number:  384 AC8

            Abstract:  Human H3 strains of influenza A virus preferentially bind cell-surface oligosaccharides containing the sequence NeuAc alpha 2,6Gal, while avian influenza strains preferentially recognize the sequence NeuAc alpha 2,3Gal. The distribution of these two types of sialic acid linkages on host respiratory epithelium, the target of influenza infection, may be a factor in the selection of the different receptor specificities observed in human and avian influenza strains. To examine the distribution of these two structures on human tracheal epithelial cells, two sialic acid specific lectins were used. The Sambucus nigra lectin (SNA), which recognizes the sequence NeuAc alpha 2,6Gal/GalNac, primarily binds to the surface of the ciliated tracheal epithelial cells, and only weakly binds to mucins in the surface goblet cells. In contrast, the Maackia amurensis lectin (MAL), which is specific for the NeuAc alpha 2,3Gal sequence, binds strongly to mucus droplets in goblet cells, but not to the surface of ciliated cells. Thus, human ciliated tracheal cells appear to contain sialyloligosaccharides preferentially recognized by human influenza strains. These findings suggest that human H3 influenza strains may have evolved a receptor specificity which favors binding to ciliated cells, and minimizes binding inhibition by respiratory mucus.

            Descriptors:  influenza A virus human metabolism, oligosaccharides metabolism, receptors, virus metabolism, trachea ultrastructure, epithelial cells, epithelium metabolism, epithelium ultrastructure, fluorescent antibody technique, fluorescent dyes diagnostic use, histocytochemistry, protein binding, receptors, virus ultrastructure, trachea cytology, trachea metabolism.

Bean, W.J. (1984). Correlation of influenza A virus nucleoprotein genes with host species. Virology 133(2): 438-42.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The RNAs coding for the nucleoproteins of a panel of influenza isolates from human and nonhuman hosts were compared by RNA-RNA hybridization to determine the extent of genetic diversity of this protein and to determine if related nucleoproteins (NP) are consistently found in viruses from certain hosts. Five nucleoprotein groups were defined. Group 1 contains nearly all of the avian influenza viruses, group 2 includes only certain viruses isolated from gulls, group 3 includes all recent equine influenza strains, group 4 contains only equine/Prague/1/56, and group 5 contains all human and swine influenza isolates. The maintenance of specific nucleoproteins in viruses from certain species suggests that these proteins have evolved functionally significant differences that favor their replication in a specific host.

            Descriptors:  cell transformation, viral, genes, structural, genes viral, influenza A virus genetics, nucleoproteins genetics, human genetics, porcine genetics, nucleic acid hybridization, RNA viral genetics, species specificity.

Bean, W.J., Y. Kawaoka, J.M. Wood, J.E. Pearson, and R.G. Webster (1985). Characterization of virulent and avirulent A/chicken/Pennsylvania/83 influenza A viruses: potential role of defective interfering RNAs in nature. Journal of Virology 54(1): 151-60.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In April 1983, an influenza virus of low virulence appeared in chickens in Pennsylvania. Subsequently, in October 1983, the virus became virulent and caused high mortality in poultry. The causative agent has been identified as an influenza virus of the H5N2 serotype. The hemagglutinin is antigenically closely related to tern/South Africa/61 (H5N3) and the neuraminidase is similar to that from human H2N2 strains (e.g., A/Japan/305/57) and from some avian influenza virus strains (e.g., A/turkey/Mass/66 [H6N2]). Comparison of the genome RNAs of chicken/Penn with other influenza virus isolates by RNA-RNA hybridization indicated that all of the genes of this virus were closely related to those of various other influenza virus isolates from wild birds. Chickens infected with the virulent strain shed high concentrations of virus in their feces (10(7) 50% egg infective dose per g), and the virus was isolated from the albumin and yolk of eggs layed just before death. Virus was also isolated from house flies in chicken houses. Serological and virological studies showed that humans are not susceptible to infection with the virus, but can serve as short-term mechanical carriers. Analysis of the RNA of the viruses isolated in April and October by gel migration and RNA-RNA hybridization suggested that these strains were very closely related. Oligonucleotide mapping of the individual genes of virulent and avirulent strains showed a limited number of changes in the genome RNAs, but no consistent differences between the virulent and avirulent strains that could be correlated with pathogenicity were found. Polyacrylamide gel analysis of the early (avirulent) isolates demonstrated the presence of low-molecular-weight RNA bands which is indicative of defective-interfering particles. These RNAs were not present in the virulent isolates. Experimental infection of chickens with mixtures of the avirulent and virulent strains demonstrated that the avirulent virus interferes with the pathogenicity of the virulent virus. The results suggest that the original avirulent virus was probably derived from influenza viruses from wild birds and that the virulent strain was derived from the avirulent strain by selective adaptation rather than by recombination or the introduction of a new virus into the population. This adaptation may have involved the loss of defective RNAs, as well as mutations, and thus provides a possible model for a role of defective-interfering particles in nature.

            Descriptors:  chickens microbiology, influenza A virus avian pathogenicity, RNA viral analysis, antigens, viral analysis, defective viruses genetics, Diptera microbiology, ducks microbiology, avian genetics, avian immunology, swine microbiology, viral interference, virus replication.

Bean, W.J., S.C. Threlkeld, and R.G. Webster (1989). Biologic potential of amantadine-resistant influenza A virus in an avian model. Journal of Infectious Diseases 159(6): 1050-6.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Amantadine has been accepted for both the treatment and prophylaxis of influenza A virus infections. Although amantadine-resistant mutants have been shown to be readily generated both in the laboratory and in children treated with rimantadine, little is known about their biologic properties, such as genetic stability, transmissibility, or pathogenicity, compared with the parental virus. This study examined these properties using an avian influenza virus, A/chicken/Pennsylvania/1370/83 (H5N2). Variants that were amantadine-resistant, virulent, and capable of competing with wild-type virus for transmission to susceptible hosts in the absence of the drug were selected. These amantadine-resistant variants were also genetically stable, showing no reversion to wild-type after six passages in birds over a period of greater than 20 d. Thus, these virus variants had no detectable biologic impairment. The mutations conferring drug resistance were in the M2 polypeptide and were identical to mutations previously described in human amantadine-resistant virus. These results suggest that resistant mutants may have the potential to threaten the effective use of amantadine and rimantadine for the control of epidemic influenza.

            Descriptors:  amantadine pharmacology, fowl plague microbiology, influenza A virus avian drug effects, amantadine therapeutic use, chickens, drug resistance, microbial, fowl plague drug therapy, fowl plague transmission, avian genetics, avian pathogenicity, mutation, RNA viral genetics, virulence.

Beard, C.W., M. Brugh, and R.G. Webster (1987). Emergence of amantadine-resistant H5N2 avian influenza virus during a simulated layer flock treatment program. Avian Diseases 31(3): 533-7.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  An experiment was designed to simulate field conditions in which preventive treatment is not initiated until after some chickens in a flock are infected with avian influenza (AI). Twelve hens began to receive amantadine hydrochloride on the day they were inoculated (day 0) with highly pathogenic AI virus, A/chicken/Pa/1370/83. These hens remained clinically normal through 8 days postinoculation (PI), but five died after day 9; mean death time (MDT) was 18 days. Three of 12 hens given amantadine beginning 1 day PI died (MDT 5.4 days), seven of 12 hens given amantadine beginning 3 days PI died (MDT 3.7 days), and all 12 inoculated hens not given amantadine died (MDT 4.9 days). The delayed mortality in the day 0 treatment group was likely due not to the original inoculum but to the emergence of a drug-resistant virus population. Virus isolated from a dead hen from that group was resistant to the actions of amantadine in both in ovo and in vivo tests. The lack of late mortality due to the drug-resistant virus in the day 1 and day 3 treatment groups, which were in close contact with the day 0 treatment group, was attributed to their becoming infected before treatment with the drug and to the development of protective immunity.

            Descriptors:  amantadine pharmacology, chickens, fowl plague prevention and control, influenza A virus avian drug effects, amantadine therapeutic use, chick embryo, drug resistance, microbial, fowl plague drug therapy.

Becht, H. (1971). Cytoplasmic synthesis of an arginine-rich nuclear component during infection with an influenza virus. Journal of Virology 7(2): 204-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  arginine metabolism, cultured cells metabolism, cytoplasm metabolism, influenza A virus avian pathogenicity, proteins biosynthesis, autoradiography, cell line, cell nucleus metabolism, chick embryo, ethanol, fibroblasts, hamsters, hydrochloric acid, kidney, precipitation, solvents, trichloroacetic acid, tritium.

Becht, H. (1969). Induction of an arginine-rich component during infection with influenza virus. Journal of General Virology 4(2): 215-20.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  arginine metabolism, influenza A virus avian metabolism, tissue culture, autoradiography, cell nucleus metabolism, chick embryo, cytoplasm metabolism, dactinomycin pharmacology, fibroblasts, leucine metabolism, lysine metabolism, tritium, virus replication.

Becht, H. (1968). Properties of erythrocytes stabilized with sulfosalicylic acid and their use in an indirect hemagglution test with influenza virus RNP-antigen. Journal of Immunology 101(1): 18-22.  ISSN: 0022-1767.

            NAL Call Number:  448.8 J8232

            Descriptors:  antigens, erythrocytes, hemagglutination tests, indicators and reagents, orthomyxoviridae, salicylic acids, sulfonic acids, complement fixation tests, immune sera, influenza A virus avian, nucleoproteins, sheep.

Becht, H. (1971). Untersuchungen uber die Biosynthese und uber den serologischen Nachweis des Ribonucleoproteid-Antigens von Influenzaviren. I. Untersuchungen uber die Bildung des RNP-Antigens und die Rolle des Zellerns bei seiner Synthese. [Studies on biosynthesis and serological demonstration of ribonucleoprotein antigen of influenza viruses. I. Studies on biosynthesis of RNP antigen and the role of cell nucleus in its synthesis].  Zeitschrift Fur Medizinische Mikrobiologie Und Immunologie 156(4): 309-30.  ISSN: 0044-3077.

            NAL Call Number:  449.8 Z3

            Descriptors:  antigens biosynthesis, influenza A virus avian immunology, antigens, viral biosynthesis, arginine, autoradiography, AZO compounds pharmacology, cell nucleus metabolism, chick embryo, fibroblasts, hemagglutinins viral biosynthesis, membranes, nucleoproteins biosynthesis, ribose, serotyping, viral proteins biosynthesis.

Becht, H. and R. Drzeniek (1968). The effect of azo dyes on myxovirus neuraminidase and on virus multiplication. Journal of General Virology 2(2): 261-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  azo compounds pharmacology, influenza A virus avian drug effects, neuraminidase antagonists and inhibitors, Newcastle disease virus drug effects, arboviruses drug effects, arboviruses growth and development, chick embryo, complement fixation tests, Congo red pharmacology, hemagglutination tests, avian growth and development, neuraminidase metabolism, Newcastle disease virus growth and development.

Becht, H., H. Gruschkau, and R. Rott (1979). The M protein of influenza viruses has no immunizing effect. Medical Microbiology and Immunology 167(4): 285-8.  ISSN: 0300-8584.

            Abstract:  Influenza A virus M protein was prepared by electrophoresis in SDS polyacrylamide gel from virus particles which had been pretreated with octylglucoside to remove the surface glycoproteins; M antigens from the influenza virus strains A/Victoria/3/75 (H3N2), A/FPV/Rostock (Hav1N1) and A/chick/Germany/49 (Hav2Neq1) did not protect mice against a lethal challenge infection with the virulent Victoria strain.

            Descriptors:  antigens, viral immunology, influenza A virus avian immunology, human immunology, viral proteins immunology, antibodies, viral biosynthesis, hemagglutination inhibition tests, immunization, influenza immunology, influenza prevention and control, mice.

Becht, H. and B. Malole (1975). Comparative evaluation of different fixation procedures and different coupling reagents for the demonstration of influenza virus-specific antibodies by the indirect hemagglutination test. Medical Microbiology and Immunology 162(1): 43-53.  ISSN: 0300-8584.

            Abstract:  The indirect hemagglutination technique has been improved by fixing the carrier erythrocytes successively with glutaraldehyde and sulfosalicylic acid. Sensitization by covalent conjugation of influenza virus antigens to the erythrocytes with various coupling reagents, which resulted in stable and highly sensitive test cells, has been defined. An economical affinity chromatography procedure using antibody-coated agarose has been developed to prepare sufficiently pure antigens from fowl plague virus-infected choriollantoic membranes.

            Descriptors:  antibodies, viral analysis, erythrocytes immunology, hemagglutination tests methods, antibody specificity, blood preservation, chromatography, affinity, cytological techniques, glutaral, hemagglutinins viral isolation and purification, influenza A virus avian immunology, salicylic acids.

Becht, H., R. Rott, and H.D. Klenk (1972). Effect of Concanavalin A on cells infected with enveloped RNA viruses. Journal of General Virology 14(1): 1-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  agglutination drug effects, lectins pharmacology, RNA viruses, agglutination tests, arboviruses, cattle, cell line, cell membrane drug effects, cultured cells microbiology, chick embryo, concanavalin A pharmacology,  fibroblasts, hamsters, HeLa cells microbiology, influenza A virus avian, kidney, cell line microbiology, Newcastle disease virus, orthomyxoviridae, polioviruses, Semliki Forest virus, simian virus 40, sindbis virus, vesicular stomatitis Indiana virus, virus diseases.

Bektemirov, T.A., S.A. Moisiadi, E.N. Kantorovich, N.V. Kaverin, and O.N. Berezina (1974). Nekotorye biologicheskie svoistva "nepol'nogo" virusa grippa. [Biological properties of "incomplete" influenza virus]. Voprosy Virusologii (2): 181-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  defective viruses pathogenicity, orthomyxoviridae pathogenicity, influenza A virus avian, interferons biosynthesis, mice, viral interference, virus replication.

Belshe, R.B. (1995). A review of attenuation of influenza viruses by genetic manipulation. American Journal of Respiratory and Critical Care Medicine 152(4, Pt. 2): S72-5.  ISSN: 1073-449X.

            Descriptors:  genetic engineering methods, influenza A virus human genetics, influenza B virus genetics, influenza vaccine genetics, adult, infant, avian immunology, human immunology, human pathogenicity, influenza B virus immunology, influenza B virus pathogenicity, influenza vaccine immunology, vaccines, attenuated genetics, vaccines, attenuated immunology, vaccines, combined genetics,  vaccines, combined immunology.

Bergelson, L.D., A.G. Bukrinskaya, N.V. Prokazova, G.I. Shaposhnikova, S.L. Kocharov, V.P. Shevchenko, G.V. Kornilaeva, and E.V. Fomina Ageeva (1982). Role of gangliosides in reception of influenza virus. European Journal of Biochemistry FEBS 128(2-3): 467-74.  ISSN: 0014-2956.

            NAL Call Number:  QP501.E8

            Abstract:  The ganglioside composition of Ehrlich ascites carcinoma (EAC) cells and the role of the individual gangliosides in binding and penetration into the cell of influenza virus were determined. EAC gangliosides identical with or close to GM3, GM2, GM1, GT1a and GT1b were characterized by thin-layer chromarography, compositional analyses, methylation analysis and mass-spectrometry. The ganglioside uptake capacity of native and neuraminidase-treated EAC cells was studied with tritium-labeled gangliosides of definite structure and the binding of influenza virus to cells was determinated by using [3H]uridine-labeled virus and by hemagglutination studies. Treatment of the cells with Vibrio cholerae neuraminidase largely decreased binding of the virus. Exogenous gangliosides with a terminal galactose unit or a penultimate galactose masked by neuraminic acid were able to restore the virus-binding capacity of neuraminidase-treated cells, however, the main ganglioside of EAC cells, GM2, which carbohydrate chain is terminated by N-acetylgalactosamine, was completely ineffective. The common carbohydrate sequence of the gangliosides showing binding activity (formula; see text) is proposed to be the main recognition structure of the influenza virus receptor on the surface of EAC cells. Penetration of labeled influenza virus into the nuclei of EAC cells was evaluated by measuring the radioactivity of the nuclei of neuraminidase-treated ganglioside-loaded cells after exposition to the labeled virus. Of all gangliosides tested only trisialogangliosides of the GT1b type were able to induce increased entry of the virus into the cells and accumulation of its radioactive component into the nuclei. It is suggested that GT1b gangliosides react specifically with the virus protein responsible for membrane fusion (apparently the hemagglutinin HA2 subunit) and thus are involved in virus penetration and delivery of the virus genome to the nuclei.

            Descriptors:  carcinoma, ehrlich tumor microbiology, gangliosides metabolism, influenza A virus avian physiology, receptors, virus metabolism, carbohydrate sequence, hemagglutination tests, kinetics, mice, neuraminidase pharmacology, receptors, virus drug effects, structure activity relationship, vibrio cholerae enzymology.

Berting, A., C. Fischer, S. Schaefer, W. Garten, H.D. Klenk, and W.H. Gerlich (2000). Hemifusion activity of a chimeric influenza virus hemagglutinin with a putative fusion peptide from hepatitis B virus. Virus Research 68(1): 35-49.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Entry of enveloped viruses is often mediated by an aminoterminal hydrophobic fusion peptide of a viral surface protein. The S domain of the hepatitis B virus surface protein contains a putative fusion peptide at position 7-18, but no systems are available to study its function directly. We tested the functionality of this peptide and a related peptide from another hepadnavirus in the context of the well-characterized influenza virus hemagglutinin H7 using gene mutation. The chimeric hemagglutinins could be expressed stably in CV 1 cells and were transported to the cell surface. The chimeras were incompletely cleaved by cellular proteases but cleavage could be completed by trypsin treatment of the cells. The chimeras did not differ in receptor binding, i.e. erythrocyte binding. Hemifusion and fusion pore formation were detected with membrane or cytosolic fluorescent dye-labeled erythrocytes as target structures of the hemagglutinin. Five of six different chimeras mediated hemifusion in 20-54% of the hemagglutinin-expressing cells, complete fusion and syncytium formation was not observed. The data suggest that the sequence 7-18 of the hepatitis B S domain may indeed initiate the first step of viral entry, i.e. hemifusion.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, hepatitis B virus metabolism, membrane fusion, viral fusion proteins metabolism, amino acid sequence, cell line, chimeric proteins genetics, chimeric proteins metabolism, hemagglutinin glycoproteins, influenza virus genetics, hepatitis B virus genetics, molecular sequence data, peptides chemistry, peptides genetics, receptors, virus metabolism, viral fusion proteins chemistry, viral fusion proteins genetics.

Betakova, T., F. Ciampor, and A.J. Hay (2005). Influence of residue 44 on the activity of the M2 proton channel of influenza A virus. Journal of General Virology 86(Pt. 1): 181-4.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The influenza A virus M2 proton channel plays a role in two stages of virus replication. The proteins of two closely related strains of the avian H7 subtype of influenza A virus, Rostock and Weybridge, were found to differ in their pH-modulating activities and activation characteristics. Of three amino acid differences at residues 27, 38 and 44 within the membrane-spanning domain, substitution at residue 44 was necessary and sufficient to account for differences in trans-Golgi pH-modulating activity, whereas changes in all three were required to switch the activation characteristics of the Weybridge M2 to those of the Rostock M2. These results not only separate the two phenomena genetically, but also indicate that the 'unique' activation characteristics of the Rostock M2 channel were selected specifically. In addition, they point to the importance of functional complementarity between the activation characteristics of the M2 channel and the pH of membrane fusion by haemagglutinin during virus entry.

            Descriptors:  influenza A virus, avian metabolism, ion channels metabolism, viral matrix proteins metabolism, amino acid sequence, cell line, Golgi apparatus chemistry, Golgi apparatus metabolism, hemagglutinins, viral metabolism, hydrogen-ion concentration, ion channels chemistry, molecular sequence data, protein structure, tertiary, protons, sequence alignment, viral matrix proteins chemistry, virus replication.

Blagoveshchenskaya, O.V. and Y.Z. Ghendon (1978). Comparative study of virion transcriptase of some influenza virus strains. Acta Virologica 22(2): 97-103.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The activities, the temperature and pH optima of in vitro functioning and stability upon heating of virion transcriptase of 10 human influenza virus A strains differing in reactogenicity and isolated in different epidemiological situations, and of fowl plague virus (FVP) were compared. As compared with virion transcriptase of human influenza virus strains studied, that of FPV had a higher pH optimum, was capable of functioning in vitro at a higher temperature and was more stable on heating. Freshly isolated and vaccine influenza virus strains on the one hand and strains isolated at the peak and in the end of an epidemic did not differ in the virion transcriptase properties. The virion transcriptase of a strain isolated from a local influenza outbreak was much less active than transcriptase of a highly epiedmic strain.

            Descriptors:  influenza A virus avian enzymology, human enzymology, RNA nucleotidyltransferases metabolism, RNA replicase metabolism, heat, hydrogen-ion concentration, influenza vaccine, species specificity, temperature, virion enzymology.

Blinov, V.M., O.I. Kiselev, S.M. Resenchuk, A.I. Brovkin, A.G. Bukrinskaia, and L.S. Sandakhchiev (1993). Analiz potentsial'nykh uchastkov rekombinatsii v genakh gemaggliutinina virusov grippa zhivotnykh v otnoshenii ikh adaptatsii k novomu khoziainu--cheloveku. [An analysis of the potential areas of recombination in the hemagglutinin genes of animal influenza viruses in relation to their adaptation to a new host--man]. Voprosy Virusologii 38(6): 263-8.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The authors tried to decode the mechanism of influenza viruses species adaptation in the process of host changing. The functionally important replacement in the surface pocket domains were revealed, particularly in the conservative region 221-241, involving fibronectin-like part. Close replacements were revealed in the region 141-161. The method of construction of heteroduplexes between hemagglutinin RNA of duck, pig, and human viruses was used. The method showed that all heteroduplexes formed recombinogene structures. An unexpected effect of directional recombination was elicited for hemagglutinin RNA heteroduplexes in cases of duck-pig and human-pig viruses. During the directional recombination the following processes took place: the receptor-binding site of animal type was transmitted to the duck virus, while the human receptor-binding site was transmitted to the pig virus. According to the experimental data, a new hypothesis is formulated: the cascade mechanism of directional recombination for duck, animal and human viruses makes it possible for the recombinant viruses to overcome interspecies barriers.

            Descriptors:  adaptation, physiological genetics, genes viral genetics, hemagglutinins viral genetics, influenza A virus avian genetics, porcine genetics, recombination, genetic genetics, amino acid sequence, ducks microbiology, human genetics, molecular sequence data,  nucleic acid heteroduplexes genetics, RNA viral genetics, swine microbiology, variation genetics genetics.

Blinova, V.K., R.Y. Podchernyaeva, and M.I. Sokolov (1975). K voprosu rekombinatsii virusov grippa cheloveka i dikikh ptits. [Recombination of influenza viruses from man and wild birds (terns)]. Sbornik Trudov Institut Virusologii Imeni D.I. Ivanovskogo, "Ekologiya Virusov" (3): 31-35.

            Descriptors:  influenza viruses, wild birds, terns, humans, virus recombination.

Bogautdinov, Z.F. (1977). Fermentingibiruyushchaya aktivnost spetsificheskoi syvorotki k neiraminidaze virusa grippa ptitsy. [Enzyme inhibiting activity of specific serum against the neuraminidase of avian influenza virus]. Doklady Vsesoyuznoi Akademii Sel'Skokhozyaistvennykh Nauk (4): 29-30.

            Descriptors:  avian influenza virus, DEAE cellulose, neuraminidase, chromatography.

Bogautdinov, Z.F. (1977). Immunoenzymology of the neuraminidase of avian influenza virus complexed with a substrate and antibodies. Soviet Agricultural Sciences (10): 39-41.  ISSN: 0735-2700.

            NAL Call Number:  S1.S68

            Descriptors:  avian influenza virus, neuraminidase, immunoenzymology, antibodies.

Bogautdinov, Z.F. and I.G. Lavrova (1976). Izuchenie svyazi mezhdu antigennoi spetsifichnost'yu i fiziko-khimicheskimi svoistvami neiraminidaz. [Relationship between antigenic specificity and physico-chemical properties of neuraminidases of avian influenza viruses]. Doklady Vsesoyuznoi Akademii Sel'Skokhozyaistvennykh Nauk (1): 37-38.

            Descriptors:  avian influenza viruses, neuraminidase, antigens, physio-chemical properties, techniques.

Bonin, J. and C. Scholtissek (1983). Mouse neurotropic recombinants of influenza A viruses. Archives of Virology 75(4): 255-68.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Recombinants with known gene constellations between fowl plague virus (FPV) and various prototype influenza virus strains have been examined for neurovirulence in suckling mice. Strongly neurotropic recombinants were obtained from crosses between FPV and the strains virus N, Hong Kong, and PR8, but not between FPV and equi 2 or swine viruses. All highly neurotropic recombinants had RNA segment 4 (HA) derived from FPV and RNA segment 2 (Ptra gene) from the other prototype strain. The derivation of two other RNA segments of the polymerase complex, namely RNA segments 3 (Pol 2) and 5 (NP) and also segment 8 (NS) can modulate these properties. For example, if in recombinants between FPV and virus N in addition to RNA segment 2 also RNA segments 3 and/or 8 are derived from virus N, neurovirulence is further enhanced, while replacement of RNA segment 5 of FPV by the corresponding segment of virus N decreases or abolishes neurovirulence. The derivation of the other genes does not seem to be relevant for neurovirulence in the crosses mentioned above. Of the prototype strains tested, the turkey England (t. Engl.) strain is the only one which was highly neurotropic for suckling mice. Recombinants between FPV and t. Engl. which have kept the HA gene of t. Engl. were still neurotropic, while those with the HA gene of FPV were completely avirulent. The results obtained demonstrated that 1. the creation of influenza virus recombinants neurotropic for mice is not a rare event; 2. one of the parents should multiply well in mouse lungs; 3. the presence of a cleavable hemagglutinin is necessary, but not sufficient. In the pair FPV/turkey England the hemagglutinin of turkey England seems to determine neurovirulence.

            Descriptors:  influenza A virus, genetics, recombination, genetic, brain microbiology, cultured cells, embryo microbiology, fibroblasts, genes viral, avian genetics, pathogenicity, kidney, lung microbiology, mice, virulence.

Borek, A. and C. Sauter (1975). Fowl plague virus adapted to human leukemia cells: interaction with normal human leukocytes and plastic surfaces. Pathologia Et Microbiologia 43(1): 62-73.  ISSN: 0031-2959.

            NAL Call Number:  448.8 Sch9

            Abstract:  An avian influenza A virus which grows well in human leukemic myeloblasts was unable to replicate in normal human leukocytes. The virus adhered during the first hours of incubation to plastic surfaces and to leukocytes and was then released into the supernatant; care should be taken not to confuse this with viral growth.

            Descriptors:  influenza A virus, avian growth and development, leukocytes microbiology, adaptation, physiological, adsorption, adult, cell adhesion, granulocytes microbiology, leukemia, myelocytic, acute, lymphocytes microbiology, monocytes microbiology, plastics, tissue culture, virus replication.

Borland, R. and B.W. Mahy (1968). Deoxyribonucleic acid-dependent ribonucleic acid polymerase activity in cells infected with influenza virus. Journal of Virology 2(1): 33-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  DNA, viral metabolism, fibroblasts enzymology, influenza A virus avian metabolism, RNA biosynthesis, RNA nucleotidyltransferases biosynthesis, chick embryo, dactinomycin pharmacology, hemagglutination, viral, RNA viral biosynthesis, tissue culture, virus replication.

Borland, R. and B.W. Mahy (1970). RNA and protein synthesis in chick embryo lung cell monolayer cultures infected with influenza virus. Archiv Fur Die Gesamte Virusforschung 30(4): 367-78.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  cytopathogenic effect, viral, lung metabolism, orthomyxoviridae pathogenicity, proteins biosynthesis, RNA biosynthesis, tissue culture, carbon isotopes, centrifugation, density gradient, chick embryo, dactinomycin pharmacology, hemadsorption, hemagglutination, influenza A virus avian growth and development, avian pathogenicity, lung pathology, orthomyxoviridae growth and development, species specificity, sucrose, tritium, uridine metabolism, valine metabolism, virus replication.

Bosch, F.X. (1985). Studies on the development of the charge heterogeneity of the influenza virus glycoproteins. Archives of Virology 83(3-4): 311-7.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The heterogeneity in charge of the influenza virus glycoproteins, hemagglutinin (HA) and neuraminidase (NA) is retained, when glycosylation is inhibited by tunicamycin (TM) or 2-deoxyglucose (2-dg). This is in contrast to the charge heterogeneity of the G protein of vesicular stomatitis virus (VSV), which is mainly due to heterogeneous sulfation of the carbohydrate side chains and therefore is abolished by the above mentioned inhibitors of glycosylation. Thus, the charge heterogeneity of influenza virus glycoproteins might be attributable to some as yet unidentified modifications of the polypeptide backbone.

            Descriptors:  hemagglutinins viral, influenza A virus avian analysis, membrane glycoproteins, neuraminidase, viral envelope proteins, viral proteins, cultured cells, chick embryo, deoxyglucose pharmacology, electrophoresis, polyacrylamide gel, hemagglutinin glycoproteins, influenza virus, avian enzymology, avian metabolism, human analysis, isoelectric focusing, isoelectric point, translation, genetic, tunicamycin pharmacology, vesicular stomatitis Indiana virus analysis.

Bosch, F.X., W. Garten, H.D. Klenk, and R. Rott (1981). Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of Avian influenza viruses. Virology 113(2): 725-35.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  hemagglutinins viral analysis, influenza A virus avian immunology, peptide hydrolases metabolism, amino acid sequence, human immunology, human pathogenicity, isoelectric point.

Bosch, F.X., A. Mayer, and R.T. Huang (1980). Simple and rapid separation of ortho- and paramyxovirus glycoproteins. Medical Microbiology and Immunology 168(4): 249-59.  ISSN: 0300-8584.

            Abstract:  The hemagglutinin (HA) and neuraminidase (NA) of influenza viruses, as well as the fusion protein (F) and hemagglutinin-neuraminidase (HN) of paramyxoviruses, have been separated in native form using a two-step procedure. The glycoproteins are efficiently extracted from virions using the on-ionic detergent octyl-beta-D-glucoside and are then applied to a column of agarose beads coupled with tyrosine-sulfanilic acid. Pure HA and F are obtained in good yield in the flow-through from this column. NA and HN bind strongly and can be eluted, albeit somewhat contaminated with HA or F, by raising the pH of the column buffer. The separated non-denatured fractions can be used for structural, functional, and antigenic studies.

            Descriptors:  glycoproteins isolation and purification, influenza A virus avian analysis, human analysis, Newcastle disease virus analysis, viral proteins isolation and purification, chromatography, affinity, detergents, hemagglutinins viral isolation and purification, neuraminidase isolation and purification.

Bosch, F.X., M. Orlich, G. Legler, R.T. Schwarz, and R. Rott (1984). Effect of inhibitors of glycosylation on proteolytic activation of avian influenza virus hemagglutinins: discrimination between tryptic cleavage and elimination of the connecting peptide. Virology 132(1): 199-204.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The glycosylation inhibitors tunicamycin (TM), 2-deoxyglucose (2-dg), bromoconduritol (BC; 3,5/4,6-6-bromo 3,4,5-trihydroxycyclohex-1-ene), and N-methyl-deoxynojirimycin (MdN) have been used to study the role of glycosylation in the two proteolytic reactions involved in the biological activation of H7 influenza virus hemagglutinins (HAs): trypsinlike cleavage and subsequent elimination of the connecting peptide. The results obtained revealed that trypsin-like cleavage of the HAs of pathogenic strains does not require glycosylation, since these HAs were efficiently cleaved in the presence of TM and 2-dg. The elimination of the connecting peptide between HA1 and HA2, however, appears to require the transfer of oligosaccharides onto the HA polypeptide, since this activity was blocked by TM and by 2-dg. Elimination was not blocked by BC or MdN, which inhibit glucose trimming and subsequent conversion of the high-mannose type to the complex type of carbohydrate.

            Descriptors:  1 deoxynojirimycin analogs and derivatives, carbohydrates metabolism, hemagglutinins viral metabolism, influenza A virus avian analysis, trypsin metabolism, deoxyglucose pharmacology, glucosamine analogs and derivatives, glucosamine pharmacology, inositol analogs and derivatives, inositol pharmacology, tunicamycin pharmacology, virion analysis.

Bosch, F.X., V. Von Hoyningen Huene, C. Scholtissek, and R. Rott (1982). The overall evolution of the H7 influenza virus haemagglutinins is different from the evolution of the proteolytic cleavage site. Journal of General Virology 61(Pt. L): 101-4.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  It has been shown previously that the pathogenicity of avian influenza A viruses depends strictly on the proteolytic cleavability of their haemagglutinins (HAs) in infected cells. In this communication, pathogenic and non-pathogenic strains of the H7 subtype have been studied by comparing the genetic relatedness of their HA genes. Some of the cleavable HAs of pathogenic strains were genetically more closely related to the uncleaved HAs than to other cleavable HAs. These data clearly demonstrate that the overall evolution of the H7 haemagglutinins is different from the evolution of the specific cleavage site.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus avian immunology, evolution, hemagglutinins viral analysis, avian genetics, avian pathogenicity, nucleic acid hybridization.

Bossart Whitaker, P., M. Carson, Y.S. Babu, C.D. Smith, W.G. Laver, and G.M. Air (1993). Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid. Journal of Molecular Biology 232(4): 1069-83.  ISSN: 0022-2836.

            NAL Call Number:  442.8 J8224

            Abstract:  We present here the three-dimensional structure of neuraminidase (E.C. 3.2.1.18) from influenza virus A/Tern/Australia/G70c/75 (N9), determined by the method of multiple isomorphous replacement, and the structure of the neuraminidase complexed with an inhibitor, 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid (DANA). Native and inhibitor complex crystals are isomorphous and belong to space group I432 with unit cell dimensions of 183.78 A. The native enzyme structure and the inhibitor complex structure have been refined at 2.5 A and 2.8 A resolution, respectively, with crystallographic R-factor values of 0.193 for the native enzyme, and 0.179 for the inhibitor complex. The current enzyme model includes 387 amino acid residues which comprise the asymmetric unit. The root-mean-square deviation from ideal values is 0.013 A for bond lengths and 1.6 degree for bond angles. The neuraminidase (NA), as proteolytically cleaved from the virus, retains full enzymatic and antigenic activity, and is a box-shaped tetramer with edge lengths of 90 A and a maximal depth of 60 A. The NA tetramers are composed of crystallographically equivalent monomers related by circular 4-fold symmetry. Each monomer folds into six antiparallel beta-sheets of four strands. The secondary structure composition is 50% beta-sheet. The remaining 50% of the residues form 24 strand-connecting loops or turns. One of the loops contains a small alpha-helix. The structure of the complex of NA with DANA, a transition state analog, has enabled us to identify and characterize the site of enzyme catalysis. The center of mass of bound inhibitor is 32 A from the 4-fold axis of the tetramer, lodged at the end of a shallow crater of diameter 16 A with a depth of 8 to 10 A. There are 12 amino acid residues that directly bind DANA, with a further six conserved amino acids lining the active site pocket. The neuraminidase inhibitor complex provides a three-dimensional model which will be used to further the understanding of enzymatic hydrolysis and aid the design of specific, antineuraminidase antiviral compounds.

            Descriptors:  influenza A virus avian enzymology, neuraminidase antagonists and inhibitors, neuraminidase chemistry, sialic acids chemistry, binding sites, influenza B virus enzymology, mercury chemistry, models, molecular, molecular conformation, N-acetylneuraminic acid, platinum chemistry, protein conformation, sialic acids metabolism, x-ray diffraction.

Brecht, H., U. Hammerling, and R. Rott (1971). Undisturbed release of influenza virus in the presence of univalent antineuraminidase antibodies. Virology 46(2): 337-43.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  antibodies, influenza A virus avian growth and development, neuraminidase isolation and purification, neuraminidase metabolism, orthomyxoviridae growth and development, centrifugation, density gradient, chick embryo, chromatography, DEAE-cellulose, fibroblasts, hemagglutination tests, immune sera, immunoglobulin g, immunoglobulins, avian enzymology, avian immunology, avian pathogenicity, neuraminic acids biosynthesis, orthomyxoviridae enzymology, orthomyxoviridae immunology, orthomyxoviridae pathogenicity, rabbits, sucrose, tissue culture, virus replication.

Breslin, J.J., L.G. Smith, and J.S. Guy (2001). Baculovirus expression of turkey coronavirus nucleocapsid protein. Avian Diseases 45(1): 136-43.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The nucleocapsid (N) gene of turkey coronavirus (TCV) was amplified by reverse transcriptase-polymerase chain reaction, cloned, and expressed in the baculovirus expression system. A recombinant baculovirus containing the TCV N gene (rBTCV/N) was identified by polymerase chain reaction and expression of TCV N protein as determined by western immunoblot analysis. Two TCV-specific proteins, 52 and 43 kDa, were expressed by rBTCV/N; one of these proteins, p52, was comparable in size to native TCV N protein. Baculovirus-expressed N proteins were used as antigen in an indirect enzyme-linked immunosorbent assay (ELISA) for detection of TCV-specific antibodies. The ELISA detected antibodies specific for TCV and infectious bronchitis virus, a closely related avian coronavirus, but did not detect antibodies specific for other avian viruses (avian influenza, avian reovirus, avian paramyxovirus 3, avian adenovirus 1, or Newcastle disease virus). These findings indicate that baculovirus-expressed TCV N protein is a suitable source of antigen for ELISA-based detection of TCV-specific antibodies in turkeys.

            Descriptors:  baculoviridae metabolism, nucleocapsid biosynthesis, nucleocapsid proteins, turkeys virology, enteritis veterinary, enteritis virology, enzyme linked immunosorbent assay veterinary, North Carolina, nucleocapsid genetics, poultry diseases virology, reverse transcriptase polymerase chain reaction veterinary.

Breuning, A. and C. Scholtissek (1986). A reassortant between influenza A viruses (H7N2) synthesizing an enzymatically inactive neuraminidase at 40 degrees which is not incorporated into infectious particles. Virology 150(1): 65-74.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Cells infected with a reassortant (113/Ho, H7N2) between A/fowl plague/Rostock/34 (FPV, H7N1) and A/Hong Kong/1/68 (H3N2) carrying RNA segments 1 and 6 of the Hong Kong virus and the residual genes of FPV, synthesized at 40 degrees a neuraminidase (NA) which is enzymatically not active and which is not incorporated into infectious particles. At 40 degrees NA accumulates in the rough endoplasmic reticulum. It contains mainly carbohydrate side chains of the mannose type, and fucose is only scarcely incorporated. At 33 degrees NA of the reassortant is overproduced, and at least some of it is active and is incorporated into viral particles. Under nonreducing conditions during PAGE its NA migrates to the same position as after heating with mercaptoethanol, in contrast to the Hong Kong parent virus. It is speculated that at 40 degrees the tetramerization of the NA in the rough endoplasmic reticulum does not function, and in this way its migration to the cytoplasmic membrane and its incorporation into infectious particles does not occur. Since 113/Ho is as pathogenic for the chicken (body temperature of 41 degrees) as is FPV, the question arises which role the NA plays in virus replication and spread in the infected organism.

            Descriptors:  influenza A virus avian genetics, human genetics, neuraminidase genetics, carbohydrate sequence, cell compartmentation, chick embryo, glycopeptides analysis, glycoproteins genetics, glycoproteins metabolism, hemagglutinins viral genetics, avian enzymology, influenza A virus human enzymology, mutation, neuraminidase metabolism, recombination, genetic, temperature, viral proteins metabolism, virus replication.

Briedis, D.J., G. Conti, E.A. Munn, and B.W. Mahy (1981). Migration of influenza virus-specific polypeptides from cytoplasm to nucleus of infected cells. Virology 111(1): 154-64.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cell nucleus metabolism, cytoplasm metabolism, influenza A virus avian metabolism, viral proteins metabolism, capsid metabolism, cell fractionation, cell line, dogs, avian growth and development, kinetics.

Bromley, P.A. and R.D. Barry (1973). Characterization of the ribonucleic acid of fowl plague virus. Archiv Fur Die Gesamte Virusforschung 42(2): 182-96.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian analysis, RNA viral analysis, autoradiography, base sequence,  centrifugation, density gradient, chick embryo, chromatography, DEAE-cellulose, chromatography, gel, densitometry, electrophoresis, polyacrylamide gel, influenza A virus avian isolation and purification, nucleic acid denaturation, phosphorus isotopes, RNA viral isolation and purification, ribonucleases, tissue culture, virus cultivation.

Bromley, P.A. and R.D. Barry (1970). Studies on the nature of influenza virus ribonucleic acid. Journal of General Microbiology 63(3): xvi.  ISSN: 0022-1287.

            NAL Call Number:  448.3 J823

            Descriptors:  influenza A virus avian analysis, RNA viral analysis, base sequence, guanine analysis.

Bron, R., A.P. Kendal, H.D. Klenk, and J. Wilschut (1993). Role of the M2 protein in influenza virus membrane fusion: effects of amantadine and monensin on fusion kinetics. Virology 195(2): 808-11.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  We have investigated the effects of the anti-influenza drug amantadine (AMT) and the proton-ionophore monensin on the membrane fusion activity of influenza virus in a liposomal model system, using a kinetic fluorescence lipid mixing assay. Fusion of influenza virus A/turkey/Oregon/71 (H7N3) with liposomes was slowed down in the presence of 2 microM AMT. The effect of AMT was not observed with an AMT-resistant mutant virus. Fusion inhibition by AMT was reversed by the proton-ionophore monensin. In fact, 1 microM monensin stimulated fusion of AMT-sensitive or -resistant virus, irrespective of the presence of AMT. The effects of AMT and monensin increased with increasing temperature. They were not observed at 25 degrees, but were very prominent at 45 degrees. Monensin did not influence the fusion rates of reconstituted viral envelopes (virosomes), which lack the nucleocapsid and the M1 protein. These results suggest that intraviral low pH facilitates influenza virus fusion, possibly by weakening interactions of the C-terminus of the viral hemagglutinin with the M1 protein and/or the viral nucleocapsid. The effect of AMT on the fusion capacity of influenza virus may contribute to the anti-influenza action of the drug in the early stages of cellular infection. However, the limited extent of the fusion inhibition suggests that the fusion step is unlikely to be the primary target of AMT.

            Descriptors:  amantadine pharmacology, influenza A virus avian metabolism, monensin pharmacology, viral matrix proteins metabolism, electrophoresis, polyacrylamide gel, immunoblotting, avian drug effects, kinetics, membrane fusion drug effects.

Brooks, M.J., J.J. Sasadeusz, and G.A. Tannock ( 2004). Antiviral chemotherapeutic agents against respiratory viruses: where are we now and what's in the pipeline? Current Opinion in Pulmonary Medicine 10(3): 197-203.  ISSN: 1070-5287.

            Abstract:  PURPOSE OF REVIEW: The emergence of severe acute respiratory syndrome in late 2002 and the recent outbreaks of avian influenza in Asia are timely reminders of the ever present risks from respiratory viral diseases. Apart from influenza, there are no vaccines and very few antiviral chemotherapeutic agents available for the prevention and treatment of respiratory viral infections-the most common cause of human illness. If the current H5N1 avian influenza outbreak ever assumes the role of a pandemic, formidable technical difficulties relating to the properties of the agent, itself, will ensure that vaccines will only become available after a significant lead time and then only to a relatively small percentage of the population. The use of existing antivirals could be critical in limiting the initial spread of a pandemic, although their use in the control of epidemics caused by nonpandemic viruses has not been evaluated. It is against this background that a review of recent developments in respiratory antivirals has been undertaken. RECENT FINDINGS: The late 1990s were a period of unprecedented activity in the development of new and much superior antivirals for the treatment of influenza infections. However, during the past 2 to 3 years and largely for commercial reasons, there has been a decline in interest in their further development by major drug companies. This situation may soon change with the possible advent of new pandemic viruses, and moves are afoot in several countries to consider the stockpiling of antivirals. The neuraminidase inhibitors zanamivir and oseltamivir, and the M2 inhibitors amantadine and rimantadine, remain the only options for controlling respiratory disease caused by influenza viruses, although the latter two could not be used against very recent H5N1 strains. There are several other neuraminidase inhibitors in development. Compounds with activity against other respiratory viruses, notably rhinoviruses, are also in development, many based on a newer knowledge of viral protein structure and function (rational drug design). SUMMARY: The following is an overview of recent papers on the further development of neuraminidase inhibitors against influenza viruses and on recent development of newer antivirals against RSV and rhinoviruses. Where possible, comparisons are made with existing antivirals. For considerations of space, this review has been structured around stages in the replication cycle of significant respiratory viruses that have been traditionally used as targets for inhibition.

            Descriptors:  antiviral agents therapeutic use, respiratory tract infections drug therapy, respiratory tract infections virology, virus diseases drug therapy, antiviral agents pharmacology, drugs investigational pharmacology, drugs investigational therapeutic use, enzyme inhibitors pharmacology, enzyme inhibitors therapeutic use, ion channels antagonists and inhibitors.

Brouillette, W.J., S.N. Bajpai, S.M. Ali, S.E. Velu, V.R. Atigadda, B.S. Lommer, J.B. Finley, M. Luo, and G.M. Air (2003). Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: Modifications of essential pyrrolidinone ring substituents. Bioorganic and Medicinal Chemistry 11(13): 2739-2749.  ISSN: 0968-0896.

            NAL Call Number:  QP550.B55

            Abstract:  We recently reported the first benzoic acid, 1-(4-carboxy-2-(3-pentylamino)phenyl)-5,5-bis(hydroxymethyl)pyrrolidin-2-one (8), that is a potent inhibitor of avian influenza A neuraminidase (N9) and, unlike other reported potent neuraminidase inhibitors, does not contain a basic aliphatic amine or guanidine nor a simple N-acetyl grouping. However, 8 was a poor inhibitor of influenza B neuraminidase. In the present study we further evaluated 8 as an inhibitor of human influenza A NA isolates, and it was effective against N2 NA but found to be 160-fold less active against N1 NA. We also synthesized analogues of 8 involving moderate modifications of essential substituents on the pyrrolidinone ring. Specifically, the aminomethyl (9), hydroxyethyl (10), and aminoethyl (11) analogues were prepared. Only the most conservative change (compound 9) resulted in continued effective inhibition of influenza A, in addition to a noteworthy increase in the activity of 9 for N1 NA. The effectiveness of 9 against influenza B neuraminidase was furthermore improved 10-fold relative to 8, but this activity remained 50-fold poorer than for type A NA.

            Descriptors:  methods and techniques, pharmacology, influenza, drug therapy, respiratory system disease, viral disease, chemical synthesis laboratory techniques.

Brown, C.C., H.J. Olander, and D.A. Senne (1992). A pathogenesis study of highly pathogenic avian influenza virus H5N2 in chickens, using immunohistochemistry. Journal of Comparative Pathology 107(3): 341-8.  ISSN: 0021-9975.

            NAL Call Number:  41.8 J82

            Abstract:  Eighteen specific pathogen-free chickens (nine hens older than 1 year and nine 15-week-old males) were inoculated with highly pathogenic avian influenza virus A/Chicken/Pennsylvania/1370/1983 (H5N2). Birds were serially killed and tissues collected for histological and immunohistochemical evaluation. In the group of older hens, disease was acute or peracute. By immunohistochemistry, antigen was abundant in capillary endothelium in multiple organs, and staining for antigen in parenchymal cells was marked in brain and heart. In the group of younger male birds, disease was subacute. Immunohistochemical staining of capillary endothelium was less pronounced and viral antigen staining was evident in the parenchymal cells of the heart, brain and kidney.

            Descriptors:  antigens, viral analysis, brain immunology, endothelium, vascular immunology, fowl plague pathology, influenza A virus avian pathogenicity, myocardium immunology, chickens, fowl plague immunology, immunohistochemistry, avian classification.

Brown, I.H., P.A. Harris, J.W. McCauley, and D.J. Alexander (1998). Multiple genetic reassortment of avian and human influenza A viruses in European pigs, resulting in the emergence of an H1N2 virus of novel genotype. Journal of General Virology 79(Pt. 12): 2947-55.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Novel H1N2 influenza A viruses which were first detected in pigs in Great Britain in 1994 were examined antigenically and genetically to determine their origins and establish the potential mechanisms for genetic reassortment. The haemagglutinin (HA) of all swine H 1 N2 viruses examined was most closely related to, but clearly distinguishable both antigenically and genetically from, the HA of human H1N1 viruses which circulated in the human population during the early 1 980s. Phylogenetic analysis of the HA gene revealed that the swine H 1 N2 viruses formed a distinct branch on the human lineage and were probably introduced to pigs shortly after 1980. Following apparent transfer to pigs the HA gene underwent genetic variation resulting in the establishment and cocirculation of genetically and antigenically heterogeneous virus populations. Genetic analyses of the other RNA segments of all swine H1N2 viruses indicated that the neuraminidase gene was most closely related to those of early 'human-like' swine H3N2 viruses, whilst the RNA segments encoding PB2, PB1, PA, NP, M and NS were related most closely to those of avian viruses, which have been circulating recently in pigs in Northern Europe. The potential mechanisms and probable progenitor strains for genetic reassortment are discussed, but we propose that the swine H1N2 viruses examined originated following multiple genetic reassortment, initially involving human H1N1 and 'human-like' swine H3N2 viruses, followed by reassortment with 'avian-like' swine H1N1 virus. These findings suggest multiple reassortment and replication of influenza viruses may occur in pigs many years before their detection as clinical entities.

            Descriptors:  influenza A virus avian genetics, human genetics, recombination, genetic, antigens, viral immunology, base sequence, DNA, viral, Europe, genes viral, genotype, hemagglutination inhibition tests, hemagglutinin glycoproteins, influenza virus genetics, avian immunology, human immunology, molecular sequence data, phylogeny, sequence analysis, DNA, swine.

Brownson, J.M. and B.W. Mahy (1979). Productive influenza virus infection of synchronized chick embryo fibroblast cells. Journal of General Virology 42(3): 579-88.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The effects of cell metabolic activity on the outcome of influenza virus infection were studied in partially synchronized chick embryo fibroblast cultures. There was no evidence to show that the time in the cell cycle at which cells were infected had any significant effect on the final virus yield. However, some differences were detected in the length of the latent period between infections established in synchronized or in stationary cells. Influenza virus could replicate in synchronized or normal cell cultures in which DNA synthesis was inhibited with 9-beta-D-arabinofuranosyladenine (ara-A).

            Descriptors:  influenza A virus avian growth and development, virus replication drug effects, cell cycle, cell division, chick embryo, DNA biosynthesis, fibroblasts, avian drug effects, tissue culture, vidarabine pharmacology.

Brugh, M. and M.L. Perdue (1991). Emergence of highly pathogenic virus during selective chicken passage of the prototype mildly pathogenic chicken/Pennsylvania/83 (H5N2) influenza virus. Avian Diseases 35(4): 824-33.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The prototype mildly pathogenic A/chicken/Pennsylvania/21525/83 (H5N2) avian influenza virus, which was isolated more than 5 months before the emergence of highly pathogenic virus in the major 1983 Pennsylvania outbreak, was examined for the presence of minority subpopulations of highly pathogenic virus. Selective serial passage of the parental mildly pathogenic virus in leghorn hens did not lead to recovery of highly pathogenic virus. However, several highly pathogenic reisolates were recovered from hens inoculated with either of two mildly pathogenic virus clones selected for their ability to efficiently produce plaques in trypsin-free chicken embryo fibroblasts. Unlike the parental virus, these reisolates caused high mortality in chickens and produced postmortem lesions typical of highly pathogenic avian influenza. Electrophoretic mobilities of the hemagglutinin glycoproteins of the highly pathogenic derivatives resembled those of the prototype highly pathogenic A/chicken/Pennsylvania/1370/83 (H5N2) virus isolated in October 1983. These results suggest that unrecognized subpopulations of highly pathogenic virus may have infected Pennsylvania chickens for several months before emerging as the clinically manifest component of the virus population.

            Descriptors:  chickens, fibroblasts microbiology, fowl plague microbiology, influenza A virus avian pathogenicity, cultured cells, chick embryo, electrophoresis, polyacrylamide gel, glycoproteins analysis, hemagglutination inhibition tests, avian chemistry, avian genetics, avian growth and development, plaque assay, RNA viral analysis, serial passage, specific pathogen free organisms, viral proteins analysis.

Bruinink, A. and O. Haller (1979). Macrophage immunity to influenza virus: in vitro and in vivo studies.  Experimental Cell Biology 47(3): 190-201.  ISSN: 0304-3568.

            NAL Call Number:  448.8 Sch9

            Abstract:  Using M-TUR, a macrophage-adapted avian influenza A virus (Hav1, Nav3), antiviral resistance of peritoneal macrophages obtained from specifically or nonspecifically immunized mice towards in vitro infection was assessed. M-TUR grew to high titers in macrophages from nonimmune mice thereby causing a marked cytopathic effect. In contrast, peritoneal macrophages from mice specifically immunized with TUR virus were not affected by infection with M-TUR in vitro. This antiviral immunity was specific: mice immunized with antigenetically unrelated influenza strains such as influenza A/Hong Kong/1/68 (H3, N2) or influenza B/Lee yielded susceptible macrophages. Specific macrophage immunity could be abrogated by trypsin treatment in vitro. Susceptible macrophages from nonimmune hosts became resistant following in vitro exposure to homologous anti-TUR sera. Peritoneal exudate cells from BCG-infected animals were less susceptible to in vitro challenge with M-TUR than control macrophages. In vivo treatment of mice with the unspecific immunostimulants BCG or Corynebacterium parvum did not protect the animals against lethal infection with a hepatotropic variant of TUR.

            Descriptors:  influenza immunology, influenza A virus immunology, macrophages immunology, antigens, viral, cross reactions, epitopes, mice, mice inbred c57bl immunology, mice inbred CBA immunology.

Bucher, D.J., I.G. Kharitonenkov, D.K. Lvov, T.V. Pysina, and H.M. Lee (1980). Comparative study of influenza virus H2 (Asian) hemagglutinins isolated from human and avian sources. InterVirology 14(2): 69-77.  ISSN: 0300-5526.

            NAL Call Number:  QR355.I5

            Abstract:  The hemagglutinin of an influenza virus isolated from a wild duck (Pintail, Anas acuta) in the USSR in 1976 had been found to be antigenically indistinguishable from the hemagglutinin of H2N2 viruses of human origin isolated in 1957. The hemagglutinins from viral preparations of the A/Anas acuta/Primorie/695/76 (H2Nav2) and A/Singapore/1/57 (H2N2) strains were purified by SDS gel chromatography as the subunits HA1 and HA2. Comparison of amino acid compositions and peptide maps of tryptic peptides containing [14C]-carboxymethylcysteine showed a striking degree of similarity between the H2 hemagglutinins.

            Descriptors:  hemagglutinins viral analysis, influenza A virus avian immunology, human immunology, amino acids analysis, ducks microbiology, peptides analysis.

Buckler White, A.J. and  B.R. Murphy (1986).  Nucleotide sequence analysis of the nucleoprotein gene of an avian and a human influenza virus strain identifies two classes of nucleoproteins. Virology 155(2): 345-55.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The nucleotide sequences of RNA segment 5 of an avian influenza A virus, A/Mallard/NY/6750/78 (H2N2), and a human influenza A virus, A/Udorn/307/72 (H3N2), were determined and the deduced amino acid sequences of the nucleoprotein (NP) of these viruses were compared to two other avian and two other human influenza A NP sequences. The results indicated that there are separate classes of avian and human influenza A NP genes that can be distinguished on the basis of sites containing amino acids specific for avian and human influenza viruses and also by amino acid composition. The human influenza A virus NP genes appear to follow a linear pathway of evolution with the greatest homology (96.9%) between A/NT/60/68 (H3N2) and A/Udorn/72, isolated only 4 years apart, and the least homology (91.1%) between A/PR/8/34 (H1N1) and A/Udorn/72, isolated 38 years apart. Furthermore, 84% of the nucleotide substitutions between A/PR/8/34 and A/NT/60/68 are preserved in the NP gene of the A/Udorn/72 strain. In contrast, a distinct linear pathway is not present in the avian influenza NP genes since the homology (90.3%) between the two avian influenza viruses A/Parrot/Ulster/73 (H7N1) and A/Mallard/78 isolated only 5 years apart is not significantly greater than the homology (90.1%) between strains A/FPV/Rostock/34 and A/Mallard/78 isolated 44 years apart and only 49% of the nucleotide substitutions between A/FPV/34 and A/Parrot/73 are found in A/Mallard/78. A determination of the rate of evolution of the human influenza A virus NP genes suggested that there were a greater number of nucleotide substitutions per year during the first several years immediately following the emergence of a new subtype in 1968.

            Descriptors:  influenza A virus genetics, nucleoproteins genetics, viral proteins genetics, amino acid sequence, base sequence, evolution, genes viral, nucleoproteins classification, RNA viral genetics, sequence homology, nucleic acid, viral proteins classification.

Buckler White, A.J., C.W. Naeve, and B.R. Murphy (1986). Characterization of a gene coding for M proteins which is involved in host range restriction of an avian influenza A virus in monkeys. Journal of Virology 57(2): 697-700.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The nucleotide sequence of the region of RNA segment 7 coding for the M1 and M2 proteins of avian influenza A/Mallard/New York/6750/78 was determined, and the deduced amino acid sequences were compared to other avian and human M protein sequences. The M2 proteins of the avian and human viruses have diverged much more than the M1 proteins, although amino acids specific for avian and human viruses were found in both M1 and M2 proteins.

            Descriptors:  genes viral, influenza A virus avian genetics, RNA viral genetics, viral proteins genetics, amino acid sequence, haplorhini microbiology, avian growth and development, messenger genetics.

Bukrinskaia, A.G. and T.A. Asadullaev (1968). Sravnitel'noe deistvie gistonov i 6-azauridina na reproduktsiiu miksovirusov. [Comparative effect of histones and 6-azauridine on the reproduction of myxoviruses]. Voprosy Virusologii 13(5): 549-54.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  histones pharmacology, orthomyxoviridae drug effects, triazines pharmacology, virus replication drug effects, influenza A virus avian drug effects, Newcastle disease virus drug effects, RNA viral antagonists and inhibitors.

Bukrinskaia, A.G., G.V. Kornilaeva, N.K. Vorkunova, N.G. Timofeeva, and G.I. Shaposhnikova (1982). Gangliozidy--spetsificheskie retseptory dlia virusa grippa. [Gangliosides--specific receptors for the influenza virus]. Voprosy Virusologii 27(6): 661-6.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The capacity of two gangliosides, GD1a and GT1b isolated from bovine brain to function as specific receptors of influenza virus was determined. A primary chick fibroblast culture was treated with neuraminidase to destroy natural receptors, the cells were loaded with gangliosides GD1a and GT1b, inoculated with 3H-uridine-labeled virus, and virus adsorption and penetration into the cell nucleus were determined. Both gangliosides were shown to restore virus adsorption to the cell surface and penetration of viral structures into the cell, GT1b facilitating more effective transportation of viral structures into the nuclei than GD1a and inducing penetration into the nuclei nearly 1.5-fold as much amount of viral structures as in native cells. The same ganglioside partially restored virus-induced hemolysis upon loading it on erythrocytes pre-treated with neuraminidase. It is concluded that ganglioside GT1b is a specific receptor for influenza virus. 3.9% of this ganglioside was found in chick fibroblast lipids.

            Descriptors:  gangliosides metabolism, orthomyxoviridae metabolism, receptors, virus metabolism, adsorption, cell nucleus metabolism, chick embryo, erythrocytes metabolism, fibroblasts metabolism, hemolysis, influenza A virus avian metabolism.

Bukrinskaia, A.G., N.V. Prokazova, G.I. Shaposhnikova, S.L. Kocharov, and S.L. Shevchenko (1982). Rol' gangliozidov v retseptsii i proniknovenii v kletku virusa grippa. [Role of gangliosides in influenza virus reception and penetration into the cell]. Doklady Akademii Nauk SSSR 263(6): 1481-4.  ISSN: 0002-3264.

            NAL Call Number:  511 P444A

            Descriptors:  cell transformation, viral drug effects, gangliosides pharmacology, influenza A virus avian pathogenicity, receptors, virus drug effects, adsorption, carcinoma, Ehrlich tumor microbiology, avian drug effects, neuraminidase pharmacology.

Bukrinskaya, A.G., A.K. Gitelman, and V.B. Martynenko (1978). Abortive infection of influenza virus in Ehrlich ascites tumor cells. Unusual fragility of virus particles. Archives of Virology 56(4): 279-90.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Noninfectious virus particles were produced in Ehrlich ascites tumor cells infected intraperitoneally with fowl plague virus. The PFU yield of virus per cell was less than 0.1 and the ratio PFU/HA units in the progeny virus was less than 10(3). The virus particles had the same morphology and size as egg-grown virus but were more fragile. They were disrupted by centrifugation through sucrose and caesium chloride gradients, but this disruption was avoided by fixing the particles with formaldehyde before centrifugation. Analysis of polypeptides by SDS-PAGE showed that ascites-grown virus particles contained reduced amounts of matrix protein compared with egg-grown virus.

            Descriptors:  carcinoma, Ehrlich tumor microbiology, influenza A virus avian growth and development, centrifugation, density gradient, avian enzymology, avian ultrastructure, mice, neoplasm transplantation, neuraminidase metabolism, peptides analysis, viral proteins analysis, virus replication.

Bukrinskaya, A.G., A.K. Gitelman, V.B. Martynenko, and T.A. Assadulaev (1979). Properties of influenza virus nucleocapsids in nonpermissive cells. Acta Virologica 23(5): 353-9.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The properties of fowl plague virus (influenza virus A) nucleocapsids isolated from the cytoplasm of infected Ehrlich ascites carcinoma cells and chick embryo cells were compared. Nucleocapsids isolated from both systems possessed similar polypeptides (P and NP) but differed in their biophysical characteristics. Nucleocapsids from ascites cells sedimented in velocity sucrose gradients slower (from 25 to 50 S) and the majority of them banded at higher density in CsCl gradients (rho 1.38 as compared to 1.34 g/ml) than nucleocapsids from chick embryo cells. In the electron microscope they appeared as thin threads 3--4 nm in diameter.

            Descriptors:  capsid analysis, influenza A virus avian analysis, viral proteins analysis, capsid biosynthesis, carcinoma, Ehrlich tumor, cultured cells, centrifugation, density gradient, chick embryo, cytoplasm analysis, avian growth and development, avian metabolism, mice, microscopy, electron.

Bullough, P.A. and P.A. Tulloch (1991). Spot-scan imaging of microcrystals of an influenza neuraminidase-antibody fragment complex. Ultramicroscopy  35(2): 131-43.  ISSN: 0304-3991.

            NAL Call Number:  QH201.U4

            Abstract:  Electron micrographs of two-dimensional microcrystals of a complex of an avian influenza virus neuraminidase and an antibody Fab fragment, termed 32/3, have been recorded using the spot-scan method of imaging. The crystals have a large unit cell (159.5 A x 159.5 A x 130.5 A) and a high solvent content (approximately 71% by volume) and are a challenging specimen for testing the spot-scan methodology. Crystalline order was preserved to beyond 4 A resolution as demonstrated by electron diffraction, using an embedding medium of a mixture of glucose and neutral potassium phosphotungstate. Using a Philips C400 computer control system interfaced to an EM420 electron microscope, and with the inclusion of additional software in the system, we have been able to record micrographs at low temperature with a relatively narrow (1500 A diameter) moving beam. There is evidence that the use of such a spot-scan beam reduces the effects of beam-induced specimen motion on the quality of micrographs. Conventional low-dose "flood-beam" images showed good isotropic optical diffraction in only 15% of cases whereas 30% of spot-scan images showed good diffraction. The best flood-beam images gave phases to only 15 A resolution after computer processing, whereas the best spot-scan images gave phases to 7 A resolution. Electron diffraction patterns were also recorded at low temperature, and the resulting diffraction amplitudes combined with phases from spot-scan images to yield a projection map of the structure. A 7 A resolution projection map of the complex is presented, and is compared with the projection map of the same avian influenza neuraminidase complexed with a different monoclonal Fab fragment, NC41, which has been solved to high resolution by X-ray diffraction.

            Descriptors:  antibodies, viral chemistry, image processing, computer assisted, immunoglobulins, Fab ultrastructure, influenza A virus avian ultrastructure, neuraminidase ultrastructure, binding sites, crystallization, crystallography, immunoglobulins, Fab chemistry, avian enzymology, avian immunology, microscopy, electron, neuraminidase chemistry, x-ray diffraction.

Burger, H., H. Steuler, and C. Scholtissek (1985). A mutant of fowl plague virus (influenza A) with an enhanced electrophoretic mobility of RNA segment 8. Journal of General Virology 66(Pt. 8): 1679-86.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  A temperature-sensitive mutant (ts 1/9) obtained by undiluted passage of fowl plague virus (FPV) at 33 degrees C carried a strong ts defect in RNA segment 6 [neuraminidase (NA) gene] and a weak ts defect in RNA segment 8 [non-structural (NS) protein Although the viral proteins have normal migration rates, the NS gene migrated during polyacrylamide gel electrophoresis (PAGE) significantly faster than the NS gene of wild-type FPV, even after denaturation by glyoxal. Despite this observation, the NS gene of ts 1/9 did not carry a deletion as shown by sequence determination. There were only five base replacements which resulted in three changes in amino acids. Three of the base replacements led to a more compact secondary structure of RNA segment 8, which seems to be responsible for the faster migration rate during PAGE and which seems to resist, at least partially, the treatment with glyoxal.

            Descriptors:  influenza A virus avian genetics, mutation, RNA viral isolation and purification, amino acid sequence, base sequence, cultured cells, chick embryo, cloning, molecular, genes, structural, genes viral, hemagglutinins genetics, neuraminidase genetics, plasmids, viral genetics, RNA directed DNA polymerase metabolism.

Bush, R.M. (2004). Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 359(1447): 1067-73.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a "mixing vessel" or intermediate host in the transmission of avian influenza to humans during the 1918 "Spanish flu" pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.

            Descriptors:  evolution, molecular, influenza transmission, influenza A virus physiology, models, biological, phylogeny, SARS virus physiology, zoonoses virology, influenza genetics, influenza A virus genetics, swine virology.

Cabezas, J.A. (1991). Etudes sur la sialidase et l'esterase des virus de la grippe. [Studies on sialidase and esterase in influenza viruses]. Annales Pharmaceutiques Francaises 49(2): 57-66.  ISSN: 0003-4509.

            NAL Call Number:  396.8 AN7

            Abstract:  The main contributions of the author and collaborators about sialidase (EC 3.2.1.18) of influenza virus types A and B and O-acetylesterase (EC 3.1.1.53) of type C are summarized. After a short introduction on the topic, the negative results obtained by the author on inhibitors are commented. Then, the peculiarities of the three procedures assayed, based on the NADH determination as a measurement for the sialidase activity, are discussed. The spectrofluorimetric measurement of NADH concentration is a more sensitive and convenient procedure than that by spectrophotometry, although it is less sensitive than that based on bioluminiscence. Sialidase activity is generally higher in influenza virus type A than in type B; however, some differences have been found between the three sub-types A analysed. Furthermore, thermal stability and stability against changes in the pH values are higher for influenza virus from ducks, followed by those from humans and, finally, by those from pigs. O-acetylesterase of influenza virus type C shows a broad specificity; it acts on O-acetyl-containing compounds which may not be sialic acids. It seems that this enzyme might contribute to facilitate the action of sialidase of influenza virus types A and B. The peculiarities of influenza virus type C suggest to include this type as a new genus in the future classification of viruses.

            Descriptors:  carboxylic ester hydrolases analysis, neuraminidase analysis, orthomyxoviridae enzymology, ducks, fowl plague enzymology, influenza enzymology, influenza A virus avian enzymology, human enzymology, porcine enzymology, influenza B virus enzymology, influenza virus C enzymology, orthomyxoviridae infections enzymology, swine.

Cameron, K.R., V. Gregory, J. Banks, I.H. Brown, D.J. Alexander, A.J. Hay, and Y.P. Lin (2000). H9N2 subtype influenza A viruses in poultry in Pakistan are closely related to the H9N2 viruses responsible for human infection in Hong Kong. Virology 278(1): 36-41.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  disease outbreaks veterinary, influenza veterinary, influenza A virus avian classification, human classification, poultry diseases virology, antigens, viral genetics, antigens, viral immunology, cloning, molecular, genome, viral, hemagglutination inhibition tests, hemagglutinins viral genetics, Hong Kong epidemiology, influenza epidemiology, avian genetics, avian immunology, human genetics, human immunology, molecular sequence data, Pakistan epidemiology, phylogeny, poultry diseases epidemiology, sequence analysis, protein, viral proteins genetics, viral proteins immunology.

Capua, I., F. Mutinelli, and M.H. Hablovarid (2002). Avian embryo susceptibility to Italian H7N1 avian influenza viruses belonging to different genetic lineages. Archives of Virology  147(8): 1611-21.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  In the present paper we report of the results of an immunohistochemical investigation to assess tissue tropism and viral replication in developing chicken, turkey, Muscovy duck and mallard duck embryos, of Italian H7N1 isolates belonging to different genetic lineages. LPAI isolates were chosen on the basis of the location in the phylogenetic tree: a progenitor strain, A/ty/Italy/977/V99, (exhibiting no additional glycosylation site, nAGS), strain A/ty/Italy/2379/V99 (AGS in position 123) and strain A/ty/Italy/3675/V99 (AGS in position 149) were selected. The latter two strains belonged to distinct lineages originating from the pool of progenitor strains. HPAI isolate A/ty/Italy/4580/V99 was also included in the study. All the embryos tested supported the growth of HPAI. The LPAI isolates replicated readily in the allantoic layer of the CAM of all the species tested, and did not grow in the developing chicken, turkey and Muscovy duck embryos. In contrast, they replicated to different extents in the respiratory tract of the developing mallard embryo, which also presented lower mortality rates than the other species. We conclude from these findings that the pathogenesis of LPAI infections in mallard embryos is different to that observed in other species, and should be investigated further.

            Descriptors:  allantois virology, chick embryo virology, chorion virology, influenza A virus avian pathogenicity, disease susceptibility, ducks, embryo loss etiology, glycosylation,  immunohistochemistry, avian genetics, turkeys.

Capua, I., C. Terregino, G. Cattoli, and A. Toffan (2004). Increased resistance of vaccinated turkeys to experimental infection with an H7N3 low-pathogenicity avian influenza virus. Avian Pathology 33(2): 158-163.  ISSN: 0307-9457.

            NAL Call Number:  SF995.A1A9

            Descriptors:  avian influenza virus, disease control, disease prevention, disease resistance, experimental infection, immune response, vaccination, turkeys.

Caric Lazar, M., C. Scholtissek, and R. Rott (1975). Effect of tetraethyl thiuram disulfide (disulfiram) on the multiplication of enveloped viruses. Archives of Virology 48(4): 297-306.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Disulfiram at concentrations between 0.1 and 0.3 mM inhibits the multiplication of Semliki Forest virus (SFV), fowl plague virus (FPV), Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and pseudorabies virus (PRV), when administered 1 hour before and during adsorption. There is, however, no inhibition of virus multiplication, when the drug is added after adsorption onto chick embryo cells. Disulfiram interferes neither with the receptors of the virus nor of erythrocytes, and it does not prevent virus adsorption. Possibly an early step in virus multiplication is affected by disculfiram. Infected cells once treated with the drug recover after some time of incubation in an ingibitor-free medium. The inhibitory state can be maintained, however, if relatively low doses of disulfiram are present in the culture medium also after adsorption. Disulfiram has no effect on macromolecular synthesis of the host cells. It has, however, a marked affect on membrane function. While virus multiplication is readily inhibited by disulfiram when chick embryo or BHK cells were investigated, virus multiplication in HeLa cells is almost resestant against the action of disulfiram.

            Descriptors:  disulfiram pharmacology, herpesviridae growth and development, herpesvirus 1, suid growth and development, influenza A virus avian growth and development, Newcastle disease virus growth and development, Semliki Forest virus growth and development, vesicular stomatitis Indiana virus growth and development, virus replication drug effects, adsorption, ditiocarb pharmacology, erythrocytes drug effects, ethanol pharmacology, influenza A virus avian drug effects, Newcastle disease virus drug effects, pseudorabies drug therapy, Semliki Forest virus drug effects, tissue culture, vesicular stomatitis Indiana virus drug effects.

Carroll, S.M. and J.C. Paulson (1985). Differential infection of receptor-modified host cells by receptor-specific influenza viruses. Virus Research 3(2): 165-79.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Influenza viruses of contrasting receptor specificity have been examined for their ability to infect receptor-modified MDCK cells containing sialyloligosaccharide receptor determinants of defined sequence. Cells were treated with sialidase to remove sialic acid and render them resistant to infection and were then incubated with sialyltransferase and CMP-sialic acid to restore sialic acid in the SA alpha 2,6Gal or SA alpha 2,3Gal linkages. The viruses A/RI/5 + /57 and A/duck/Ukraine/1/63, previously shown to exhibit preferential binding of SA alpha 2,6Gal and SA alpha 2,3Gal linkages, respectively, were found to exhibit differential infection of the receptor-modified cells in accord with their receptor specificity. Coinfection of SA alpha 2,3Gal derivatized cells with a mixture of the two viruses resulted in selective propagation of the SA alpha 2,3Gal-specific A/duck/Ukraine/1/63 virus. The results demonstrate the potential for cell surface receptors to mediate selection of receptor-specific variants of influenza virus.

            Descriptors:  influenza A virus avian metabolism, human metabolism, oligosaccharides metabolism, receptors, virus metabolism, adsorption, antibodies, viral analysis, binding sites, cell line, dogs, erythrocytes microbiology, hemagglutinins viral, avian immunology, human immunology, kidney, neuraminidase metabolism, receptors, virus genetics, receptors, virus immunology, sialic acids metabolism, sialyltransferases metabolism, species specificity, viral proteins analysis.

Carter, M.J. and B.W. Mahy (1982). Incomplete avian influenza A virus displays anomalous interference. Archives of Virology 74(1): 71-6.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian physiology, viral interference, cultured cells, chick embryo, defective viruses physiology, fibroblasts, kinetics, probability.

Carter, M.J. and B.W. Mahy (1982). Synthesis of RNA segments 1-3 during generation of incomplete influenza A (fowl plague) virus. Archives of Virology 73(2): 109-19.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Incomplete influenza A virus (fowl plague Dobson strain) was prepared by undiluted passage in primary chick embryo fibroblast cells. Analysis of released virus RNA revealed a deficiency in RNA segments 1-3, characteristic of incomplete virus formation. The virus yield from a high multiplicity infection with standard virus always showed this deficiency, even when analysed as early as 6 hours post-infection, whereas infection at low multiplicity gave rise to virus indistinguishable in RNA composition from the parent virus. The relative amounts of intracellular, non-polyadenylated, complementary RNA (template RNA) were found to reflect accurately the eventual RNA composition of released virus, and were altered in phase with PFU:HAU ratio, throughout a von Magnus cycle.

            Descriptors:  defective viruses growth and development, influenza A virus avian growth and development, RNA viral biosynthesis, cultured cells, chick embryo, defective viruses metabolism, avian metabolism, kinetics, plaque assay, templates, genetic.

Caton, A.J. and J.S. Robertson (1980). Structure of the host-derived sequences present at the 5' ends of influenza virus mRNA. Nucleic Acids Research 8(12): 2591-603.  ISSN: 0305-1048.

            NAL Call Number:  QD341.A2N8

            Abstract:  Nucleotide sequence analysis of the terminal virus-coded regions of a clone of the matrix gene of influenza virus indicated that the region corresponding to the 5' end of the mRNA contains an additional 13 non-virus coded nucleotides. Using the dideoxy-chain termination sequencing method with a restriction fragment derived from this clone, we have determined that the 5' ends of matrix gene mRNAs contain a heterogenous sequence of 9-15 nucleotides. In addition, the data indicate that the 3' terminal nucleotide of matrix gene virion RNA is not transcribed into mRNA, transcription of influenza virus-specific sequences commencing with the penultimate nucleotide at the 3' end of viron RNA.

            Descriptors:  influenza A virus avian analysis, RNA, messenger, viral, base sequence, cloning, molecular, DNA restriction enzymes, DNA, recombinant.

Cattoli, G., V. Brasola, and I. Capua (2003). Plaque morphology of Italian H7N1 LPAI isolates in MDCK cells and in primary cells of different avian species. Avian Diseases 47(Special Issue): 1161-1163.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The morphology of plaques induced by Italian, H7N1, low-pathogenic avian influenza (LPAI) viruses belonging to different lineages was investigated in primary chicken, turkey, Muscovy duck, and mallard duck kidney cells and in MDCK cells in the absence of trypsin. LPAI isolates were selected on the basis of the location in the phylogenetic tree: 977/V99 (located at the root, no additional glycosylation site (nAGS)), 2379/V99 (AGS in position 123), and 3675/V99 (AGS in position 149). Different isolates did not induce plaques with a statistically significant different size in MDCK cells. However, in primary cells of different avian origin, the presence or absence of AGS significantly influenced plaque size. Generally speaking, 977/V99 was the least efficient at plaquing in all cells, while 2379/V99 (AGS in position 123) plaqued more efficiently in turkey cells and 3675/V99 (AGS in position 149) in chicken cells. The presence of either AGS induced statistically significant larger plaques in cells of waterfowl origin.

            Descriptors:  cell biology, infection, avian influenza, infectious disease, respiratory system disease, viral disease, cell culture culturing techniques, laboratory techniques, glycosylation sites plaque morphology.

Chambers, T.M. and R.G. Webster (1987). Defective interfering virus associated with A/Chicken/Pennsylvania/83 influenza virus. Journal of Virology 61(5): 1517-23.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The A/Chicken/Pennsylvania/1/83 influenza virus, isolated from a respiratory infection of chickens, is an avirulent H5N2 virus containing subgenomic RNAs (W.J. Bean, Y. Kawaoka, J.M. Wood, J.E. Pearson, and R.G. Webster, J. Virol. 54:151-160, 1985). We show here that defective interfering particles are present in this virus population. The virus had a low ratio of plaque-forming to hemagglutinating units and produced interference with standard virus multiplication in infectious center reduction assays. Subgenomic RNAs were identified as internally deleted polymerase RNAs. We have confirmed that this virus protects chickens from lethal H5N2 influenza virus infection. This protective effect appeared to be due to the inhibition of virulent virus multiplication. Additionally, subgenomic RNAs derived from polymerase RNAs were detected in 5 of 18 RNA preparations from animal influenza virus isolates. Therefore, defective interfering particles are sometimes produced in natural influenza virus infections, not just under laboratory conditions. These particles may be capable of suppressing the pathogenic effect of virulent virus infections in nature.

            Descriptors:  defective viruses genetics, influenza A virus avian genetics, DNA directed RNA polymerases genetics, defective viruses growth and development, genes viral, avian growth and development, viral genetics, viral interference, virus replication.

Chambers, T.M., S. Yamnikova, Y. Kawaoka, D.K. Lvov, and R.G. Webster (1989). Antigenic and molecular characterization of subtype H13 hemagglutinin of influenza virus. Virology 172(1): 180-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Influenza A viruses with subtype H13 hemagglutinin display an unusual host range. Although common in shorebirds, they are very rare or absent in wild ducks; additionally, H13 viruses have been isolated from a whale. To study the molecular basis for this host range, we have determined the complete nucleotide sequences of the hemagglutinin genes of three H13 influenza viruses from different species or geographical areas: A/gull/Maryland/77, A/gull/Astrachan (USSR)/84, and A/pilot whale/Maine/84. Based on the deduced amino acid sequences, H13 hemagglutinin shares the basic structure of other type A hemagglutinin subtypes such as H3, but has clearly diverged from other completely sequenced subtypes. Unique features of H13 hemagglutinin include the occurrence, near the receptor binding pocket, of residues Arg/Lys-227 and Trp-229 (H3 numbering); the significance of these are unknown. The sequence of the HA1-HA2 cleavage site resembles those of avirulent avian influenza viruses. The whale H13 hemagglutinin is similar to those from gulls, supporting the hypothesis that influenza viruses from avian sources can enter marine mammal populations but are probably not permanently maintained there. Antigenic analysis using a panel of monoclonal antibodies suggests that, like other subtypes, H13 viruses are heterogeneous, with different antigenic variants predominating in the eastern versus the western hemispheres.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, amino acid sequence, base sequence, genes viral, hemagglutinins viral classification, hemagglutinins viral genetics, avian classification, influenza A virus avian genetics, molecular sequence data, RNA viral genetics.

Chen Hualan, Yu Kangzhen, and Tian Guobin (1997). Amplification and cloning of haemagglutinin genes of avian influenza virus of H5 and H7 subtypes by RT-PCR. Chinese Journal of Animal and Poultry Infectious Diseases (2): 16-18.  ISSN: 1001-6961.

            Descriptors:  poultry, avian influenza virus, DNA, nucleotide sequence, molecular cloning, acids, domestic animals, genetic engineering, genomes, influenza virus, livestock, nucleic acids, nucleic compounds, organic acids, orthomyxoviridae, useful animals, viruses.

Chepulis, G.K., A.F. Bocharov, and V.M. Zhdanov (1967). Ionoobmennaia khromatografiia virusa klassicheskoi chumy ptits na tselliuloznykh obmennikakh. [Ion-exchange chromatography of classical fowl plague virus on cellulose exchangers]. Voprosy Virusologii 12(4): 439-45.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  influenza A virus avian isolation and purification, cellulose, chromatography, ion exchange.

Chepulis, G.K. and V.M. Zhdanov (1970). Cellular antigens in myxo- and paramyxoviruses as revealed by immunodiffusion methods. Experientia  26(10): 1141-3.  ISSN: 0014-4754.

            NAL Call Number:  475 Ex7

            Descriptors:  abo blood group system analysis, antigens analysis, erythrocytes immunology, fetal membranes immunology, haptens analysis, immunodiffusion, immunoelectrophoresis, influenza A virus avian immunology, kidney immunology, Newcastle disease virus immunology, parainfluenza virus 1, human immunology, guinea pigs, immunity, cellular, methods, rabbits, rats.

Chepulis, G.S., I.U.S. Derkach, and V.M. Zhdanov (1972). Belkovye komponenty virusa klassicheskoi chumy ptits i virusa bolezni N'iukasla. [Protein components of classical fowl plague virus and Newcastle disease virus]. Voprosy Virusologii 17(1): 48-52.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  influenza A virus avian analysis, Newcastle disease virus analysis, viral proteins analysis, antigens, viral analysis, centrifugation, density gradient, electrophoresis, disc, immunodiffusion.

Chepulis, G.S., V.M. Zhdanov, I. Nas, I. Cherba, and K. Rozha (1971). Vyiavlenie kletochnykh antigenov u miksovirusov i paramiksovirusov metodami immunodiffuzii. [Detection of cellular antigens in myxoviruses and paramyxoviruses by the immunodiffusion method]. Voprosy Virusologii 16(1): 62-70.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  antigens analysis, influenza A virus avian immunology, Newcastle disease virus immunology, orthomyxoviridae immunology, parainfluenza virus 1, human immunology, antigens, viral analysis, guinea pigs, immunodiffusion, immunoelectrophoresis, rabbits, rats, species specificity.

Cherednichenko, O.G., Z.M. Biiasheva, and N.B. Akhmatullina (2001). Geneticheskii analiz retsessivnykh letal'nykh mutatsii, indutsirovannykh virusom grippa v X-khromosome Drosophila melanogaster. [Genetic analysis of recessive lethal mutations induced by the influenza virus in the X chromosome of Drosophila melanogaster]. Genetika  37(7): 908-14.  ISSN: 0016-6758.

            NAL Call Number:  QH431.A1G4

            Abstract:  Mutagenic potential of the influenza virus was evaluated. Based on its capacity of inducing recessive lethal mutations in the X chromosome of  Drosophila melanogaster, the influenza virus can be classified as a moderate-activity mutagen. Its mutagenicity does not depend on ability to reproduce in the cell system. This virus was shown to disrupt formation of the wing, particularly wing vein M1 + 2. Cytogenetic examination of polytene X chromosomes bearing recessive lethal mutations in Drosophila salivary glands did not reveal chromosome rearrangements. These lethals are assumed to be small deletions or point mutations. The determination of the lethal activity stage of these mutations showed that they disrupt the expression of genes functioning at various developmental stage of Drosophila. Two of them were conditionally lethal (temperature-sensitive). Two of 15 mutations analyzed were mapped to region 2B9-10-3C10-11.

            Descriptors:  Drosophila melanogaster genetics, Drosophila melanogaster virology, influenza A virus avian genetics, mutagenesis, X chromosome genetics, genes, lethal, genes, recessive, point mutation.

Chiu, S.Y., H.K. Shieh, J.H. Shien, S.Y. Tai, and L.H. Lee (1994). Preparation of monoclonal antibody against avian influenza virus H5N9 strain. Journal of the Chinese Society of Veterinary Science 20(1): 40-50.  ISSN: 0253-9179.

            NAL Call Number:  SF604.C54

            Abstract:  The spleen of BALB/c mice, which had been immunized five times with purified avian influenza virus, H5N9 strain, and had good antibody response, was harvested; the spleen cells were fused with NS-1 myeloma cells. After a screening for specific antibody production with the ELISA test, 18 of 460 wells showed strong positive reactions. Three further subclonings established nine strains of hybridoma with stable activities of secreting monoclonal antibodies. The isotypes of the nine monoclonal antibodies were all IgG1, and all their light chains also belong to the kappa chain. The antibodies were applied on CEF cultures infected with AIV H5N9 by means of indirect fluorescent antibody staining. Fluorescence was observed among the cell cytoplasm only. All monoclonal antibodies had HI and neutralization abilities, but formed no precipitation line in a immunodiffusion test. One antibody reacted with viral polypeptide, which was HA2 antigen with molar mass 28 kD, according to the western blotting test. In order to detect the specificity, we reacted the monoclonal antibody with AIV subtypes H1 through H12, respectively, according to the HI test. Besides H5N9, the antibody reacted with strain H8N4, but not H8N6. Viral protein analysis by means of SDS-PAGE revealed that both H5N9 and H8N4 had common peptide bands 69, 57, 48, 37 and 28 kD, especially the peptide of HA2, 28 kD.

            Descriptors:  immune system, infection, microbiology, pathology, pharmacology, veterinary medicine, vaccination viral protein analysis.

Chizhov, N.P. (1974). Protivovirusnoe deistvie nukleaz i gistonov [Antiviral action of nucleases and histones]. Voprosy Virusologii (6): 647-52.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  antiviral agents pharmacology, deoxyribonucleases pharmacology, histones pharmacology, ribonucleases pharmacology, adenoviridae drug effects, adenoviridae infections drug therapy, antiviral agents therapeutic use, aphthovirus drug effects, conjunctivitis drug therapy, DNA, viral biosynthesis, deoxyribonucleases therapeutic use, encephalitis virus, Venezuelan equine drug effects, encephalitis viruses, tick borne drug effects, herpesviridae infections drug therapy, histones therapeutic use, influenza A virus avian drug effects, keratitis, dendritic drug therapy, meningitis, viral drug therapy, Newcastle disease virus drug effects, orthomyxoviridae drug effects, polioviruses drug effects, RNA viral biosynthesis, ribonucleases therapeutic use, simplexvirus drug effects, vaccinia virus drug effects, vesicular stomatitis Indiana virus drug effects, virus replication drug effects.

Choi, Y.K., S.M. Goyal, M.W. Farnham, and H.S. Joo (2002). Phylogenetic analysis of H1N2 isolates of influenza A virus from pigs in the United States. Virus Research 87(2): 173-9.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Twenty-four H1N2 influenza A viruses were newly isolated from pigs in the United States. These isolates originated from 19 farms in 9 different swine producing states between 1999 and 2001. All farms had clinical histories of respiratory problem and/or abortion. The viral isolates were characterized genetically to determine the origin of all eight gene segments. The results showed that all H1N2 isolates were reassortants of classical swine H1N1 and triple reassortant H3N2 viruses. The neuraminidase (NA) and PB1 genes of the H1N2 isolates were of human origin, while the hemagglutinin (HA), nucleoprotein (NP), matrix (M), non-structural (NS), PA and PB2 polymerase genes were of avian or swine origin. Fifteen of the 24 H1N2 isolates were shown to have a close phylogenic relationship and high amino acid homology with the first US isolate of H1N2 (A/SW/IN/9K035/99). The remaining nine isolates had a close phylogenic relationship with classical swine influenza H1N1 in the HA gene. All other genes including NA, M, NP, NS, PA, PB1 and PB2 showed a close phylogenic relationship with the H1N2 (A/SW/IN/9K035/99) strain and triple reassortant H3N2 viruses. However, PB1 genes of two isolates (A/SW/KS/13481-S/00, A/SW/KS/13481-T/00) were originated from avian influenza A virus lineage. These results suggest that although there are some variations in the HA genes, the H1N2 viruses prevalent in the US swine population are of a similar genetic lineage.

            Descriptors:  influenza A virus, porcine genetics, antigens, viral, hemagglutinin glycoproteins, influenza virus genetics, porcine classification, porcine enzymology, porcine isolation and purification, molecular sequence data,  neuraminidase genetics, phylogeny, swine, United States, variation genetics.

Chucholowius, H.W. and R. Rott (1972). A new method for purification of myxoviruses by zonal centrifugation with two different sucrose density gradients. Proceedings of the Society for Experimental Biology and Medicine, New York, NY 140(1): 245-7.  ISSN: 0037-9727.

            NAL Call Number:  442.9 So1

            Descriptors:  orthomyxoviridae isolation and purification, centrifugation, density gradient, centrifugation, zonal, influenza A virus avian isolation and purification, methods, Newcastle disease virus isolation and purification, sucrose.

Ciampor, F., P.M. Bayley, M.V. Nermut, E.M. Hirst, R.J. Sugrue, and A.J. Hay (1992). Evidence that the amantadine-induced, M2-mediated conversion of influenza A virus hemagglutinin to the low pH conformation occurs in an acidic trans Golgi compartment. Virology 188(1): 14-24.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Amantadine treatment of cells infected with H7 strains of influenza A viruses causes an M2 protein-mediated conversion of hemagglutinin (HA) from its native to its low pH conformation. Immunofluorescence and electron microscopic observations showed that the structural alteration and hence drug action occur shortly after HA exits from the Golgi complex during its passage through the strans Golgi region. Using the DAMP/anti-DNP pH probe it is evident that virus infection causes increased acidity of the trans Golgi region and that vesicles containing low pH HA in amantadine-treated virus-infected cells are particularly acidic. These results indicate therefore that the alteration in HA is the direct consequence of exposure to an adverse low pH and provide further support for the conclusion that the M2 protein, the target of amantadine action, is involved in regulating vesicular pH, a function important for the correct maturation of the HA glycoprotein.

            Descriptors:  amantadine pharmacology, Golgi apparatus metabolism, hemagglutinins viral chemistry, influenza A virus avian drug effects, cell compartmentation, cultured cells, fluorescent antibody technique, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral drug effects, hemagglutinins viral metabolism, hydrogen-ion concentration, avian ultrastructure, microscopy, immunoelectron, monensin pharmacology, protein conformation drug effects, temperature.

Ciampor, F., C.A. Thompson, S. Grambas, and A.J. Hay (1992). Regulation of pH by the M2 protein of influenza A viruses. Virus Research 22(3): 247-58.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Inhibition of the function of the M2 protein by amantadine can cause a conformational change in the haemagglutinin (HA) of H7 influenza A viruses and the consequent expression of the low pH form of the glycoprotein on the surface of virus-infected cells. Immunofluorescence studies showed that this conversion occurs shortly after HA exists from the Golgi complex apparently during its transport through the trans Golgi network and using the pH probe, DAMP/anti-DNP, that it is the direct result of reduced vesicular pH. The lowest pHs encountered were estimated using mutant HAs differing in pH stability to be approximately 5.2 and 5.6 in virus-infected CEF or MDCK cells, respectively, in the absence of functional M2. Depending on the particular M2, this protein was responsible for increases in vesicular pH of up to 0.8 units. The influence of mutations in both HA and M2 on the maturation of native HA illustrates the important relationship between the structural and functional properties of these two proteins. Using the fluorescent probe SNARF-1 the M2 protein was also shown to be largely responsible for the 0.3-0.4 unit reduction in intracellular pH of virus-infected cells. The data thus provide further evidence for the pH regulatory function of M2 and its importance for the maturation of the HA glycoprotein.

            Descriptors:  influenza A virus avian physiology, viral matrix proteins physiology, amantadine pharmacology, cell line, fluorescent antibody technique, hemagglutination, viral, hydrogen-ion concentration.

Ciampor, F. and P. Turcan (1972). Electron microscopy of tissue culture cells infected with myxoviruses. II. Nucleo-cytoplasmic changes in fowl plague virus-infected cells. Acta Virologica 16(3): 177-82.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  cell nucleus microbiology, cultured cells microbiology, cytoplasm microbiology, influenza A virus avian growth and development, orthomyxoviridae growth and development, cell membrane microbiology, cell nucleolus, cultured cells cytology, chick embryo, cytopathogenic effect, viral, hamsters, inclusion bodies, viral, kidney cytology, microscopy, electron, time factors, virus replication.

Clements, M.L., S.D. Sears, K. Christina, B.R. Murphy, and M.H. Snyder (1989). Comparison of the virologic and immunologic responses of volunteers to live avian-human influenza A H3N2 reassortant virus vaccines derived from two different avian influenza virus donors. Journal of Clinical Microbiology 27(1): 219-22.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  We compared the abilities of the six internal RNA segments of two avian influenza viruses, A/Mallard/Alberta/88/76 (H3N8) and A/Mallard/NY/6750/78 (H2N2), to confer attenuation on wild-type human influenza A/Bethesda/1/85 (H3N2) virus in seronegative adult volunteers. Live avian-human influenza A reassortant virus vaccines derived from either avian virus parent were comparable in the following properties: safety, infectivity, immunogenicity, and genetic stability. Since the avian influenza A/Mallard/Alberta/76 virus offered no clear advantage as a donor virus, we will conduct our future evaluations on live influenza A virus reassortants derived from the more extensively characterized avian influenza A/Mallard/NY/78 virus.

            Descriptors:  antibodies, viral biosynthesis, influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine immunology, dose response relationship, immunologic, electrophoresis, polyacrylamide gel, enzyme linked immunosorbent assay, genes viral, hemagglutination inhibition tests, avian genetics, avian physiology, human genetics, human physiology, influenza vaccine adverse effects, vaccines, attenuated adverse effects, vaccines, attenuated immunology, vaccines, synthetic adverse effects, vaccines, synthetic immunology, virus replication.

Clements, M.L., M.H. Snyder, A.J. Buckler White, E.L. Tierney, W.T. London, and B.R. Murphy (1986). Evaluation of avian-human reassortant influenza A/Washington/897/80 x A/Pintail/119/79 virus in monkeys and adult volunteers. Journal of Clinical Microbiology 24(1): 47-51.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  A reassortant influenza A virus was produced by mating an avian influenza A/Pintail/Alberta/119/79 (H4N6) virus with wild-type human influenza A/Washington/897/80 (H3N2) virus. The avian-human influenza A reassortant virus contained the genes coding for the hemagglutinin and neuraminidase surface antigens of the human influenza wild-type virus and the six other RNA segments (internal genes) of the avian influenza A virus donor. In the lower respiratory tract of squirrel monkeys, this avian-human influenza reassortant virus, like its avian influenza A parent virus, was restricted approximately 100-fold in replication compared with the wild-type human influenza A virus. Despite this restriction of replication, infection of monkeys with the avian-human influenza A reassortant virus induced resistance to wild-type human influenza A virus challenge. In comparison with the wild-type human influenza A virus, the avian-human influenza A reassortant was also fully attenuated when 10(5.5) to 10(7.5) 50% tissue culture infective doses were administered to susceptible adult volunteers. Attenuation was indicated by a more than 300-fold reduction in virus shedding and lack of reactogenicity. The reassortant virus did not spread to susceptible contacts and could not be isolated from the blood or stools of infected adults. The 50% human infectious dose was 10(6.2) 50% tissue culture infective dose, indicating that this reassortant virus is only slightly less infectious for adults than a similarly derived avian-human influenza A/Washington/80 X A/Mallard/78 reassortant virus. These findings suggest that the avian influenza A/Pintail/79 virus may be a satisfactory donor of attenuating genes for production of live, attenuated avian-human influenza A reassortant virus vaccines.

            Descriptors:  influenza A virus human immunology, immunology, influenza vaccine immunology, adolescent, adult, genes viral, influenza immunology, influenza prevention and control, human genetics, genetics, influenza vaccine adverse effects, saimiri, vaccines, attenuated adverse effects, vaccines, attenuated immunology, virus replication.

Clements, M.L., E.K. Subbarao, L.F. Fries, R.A. Karron, W.T. London, and B.R. Murphy (1992). Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers. Journal of Clinical Microbiology 30(3): 655-62.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  The transfer of six internal RNA segments from the avian influenza A/Mallard/New York/6750/78 (H2N2) virus reproducibly attenuates human influenza A viruses for squirrel monkeys and adult humans. To identify the avian influenza A virus genes that specify the attenuation and host range restriction of avian-human (ah) influenza A reassortant viruses (referred to as ah reassortants), we isolated six single-gene reassortant viruses (SGRs), each having a single internal RNA segment of the influenza A/Mallard/New York/6750/78 virus and seven RNA segments from the human influenza A/Los Angeles/2/87 (H3N2) wild-type virus. To assess the level of attenuation, we compared each SGR with the A/Los Angeles/2/87 wild-type virus and a 6-2 gene ah reassortant (having six internal RNA segments from the avian influenza A virus parent and two genes encoding the hemagglutinin and neuraminidase glycoproteins from the wild-type human influenza A virus) for the ability to replicate in seronegative squirrel monkeys and adult human volunteers. In monkeys and humans, replication of the 6-2 gene ah reassortant was highly restricted. In humans, the NS, M, PB2, and PB1 SGRs each replicated significantly less efficiently (P less than 0.05) than the wild-type human influenza A virus parent, suggesting that each of these genes contributes to the attenuation phenotype. In monkeys, only the NP, PB2, and possibly the M genes contributed to the attenuation phenotype. These discordant observations, particularly with regard to the NP SGR, indicate that not all genetic determinants of attenuation of influenza A viruses for humans can be identified during studies of SGRs conducted with monkeys. The PB2 and M SGRs that were attenuated in humans each exhibited a new phenotype that was not observed for either parental virus. Thus, it was not possible to determine whether avian influenza virus PB2 or M gene itself or a specific constellation of avian and human influenza A virus specified restriction of virus replication in humans.

            Descriptors:  influenza A virus avian genetics, human genetics, adult, base sequence, genes viral, human pathogenicity, human physiology, influenza vaccine isolation and purification, molecular sequence data, RNA viral genetics, saimiri, transfection, vaccines, attenuated isolation and purification, virulence genetics, virus replication genetics.

Cmarkova, J., D. Cmarko, E. Zavodska, A. Ellinger, M. Pavelka, and F. Ciampor (1995). Ultrastructural lectinocytochemistry of fowl plague virus-infected and uninfected MDCK cells. Acta Virologica 39(2):  85-93.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Using horseradish peroxidase (HRP)-conjugated lectins for pre-embedding labelling we have shown differences in ultrastructural localization of saccharides in cell compartments of fowl plague (FP) virus-infected and uninfected MDCK cells. Lectinochemical staining of the cell compartments in the case of FP virus-infected MDCK cells was less intensive as compared with uninfected cells. Also certain differences in the staining of subcompartments of cell organells were seen. Staining of uninfected cells with Pisum sativum agglutinin (PSA)-HRP revealed an extensive visualization of Golgi complex, mainly its cis-part, TGN vesicles and lysosomes. Staining of FP virus-infected cells with the same lectin marked very lightly rough endoplasmic reticulum and not at all the Golgi complex. Staining with Erythrina cristagalli agglutinin (ECA)-HRP revealed a picture very similar to PSA-HRP staining of uninfected and FP virus-infected cells. The differences in the lectinochemical staining of cell organelles of FP virus-infected and uninfected cells may be connected with the inhibition of cell protein synthesis during FP virus morphogenesis.

            Descriptors:  influenza A virus avian chemistry, plant lectins, antibodies, monoclonal immunology, cell line, dogs, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral metabolism, hemagglutinins viral ultrastructure, immunoenzyme techniques, avian ultrastructure, lectins metabolism.

Condobery, P.K. and R.D. Slemons (1992). Biological properties of waterfowl-origin type A influenza viruses in chickens. Avian Diseases 36(1): 17-23.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The replicative abilities and tissue tropism properties of 13 non-pathogenic or low-pathogenic waterfowl-origin type A influenza isolates recovered in 1986 were examined in chickens. Following intravenous challenge, reisolation of challenge virus was attempted from swabs of the luminal surfaces of the cloaca, jejunum, ileum, bursa, trachea, and air sacs and from swabs of bone marrow and liver tissues. Virus-isolation attempts were also accomplished on brain, thymus, spleen, pancreas, gonad, kidney, blood, and lung tissues. The overall frequency of influenza virus recovery for each experiment ranged from 3.1% to 49.3%. For all experiments combined, 58.3% of the kidney tissues and 62.9% of the cloacal swab samples collected on days 1 to 10 postinoculation were positive for challenge virus recovery. Virus titers up to 10(8.7) mean embryo infective dose per gram of kidney tissue were demonstrated in clinically normal chickens. Distinct biological variations and nephrotropism appear to exist among the corporate properties of virus populations making up each of the 13 waterfowl-origin type A influenza isolates.

            Descriptors:  chickens, fowl plague microbiology, influenza A virus avian physiology, virus replication, antibodies, viral blood, chick embryo, cloaca microbiology, avian immunology, avian isolation and purification, kidney microbiology, serial passage, specific pathogen free organisms.

Connor, R.J., Y. Kawaoka, R.G. Webster, and J.C. Paulson (1994). Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 205(1): 17-23.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The receptor specificity of 56 H2 and H3 influenza virus isolates from various animal species has been determined to test the relevance of receptor specificity to the ecology of influenza virus. The results show that the receptor specificity of both H2 and H3 isolates evaluated for sialic acid linkage specificity and inhibition of hemagglutination by horse serum correlates with the species of origin, as postulated earlier for H3 strains based on a limited survey of five human, three avian, and one equine strain. Elucidation of the amino acid sequence of several human H2 receptor variants and analysis of known sequences of H2 and H3 isolates revealed that receptor specificity varies in association with an amino acid change at residues 228 in addition to the change at residue 226 previously documented to affect receptor specificity of H3 but not H1 isolates. Residues 226 and 228 are leucine and serine in human isolates, which preferentially bind sialic acid alpha 2,6-galactose beta 1,4-N-acetyl glucosamine (SA alpha 2,6Gal), and glutamine and glycine in avian and equine isolates, which exhibit specificity for sialic acid alpha-2,3-galactose beta-1,3-N-acetyl galactosamine (SA alpha 2,3Gal). The results demonstrate that the correlation of receptor specificity and species of origin is maintained across both H2 and H3 influenza virus serotypes and provide compelling evidence that influenza virus hosts exert selective pressure to maintain the receptor specificity characteristics of strains isolated from that species.

            Descriptors:  influenza A virus avian metabolism, human metabolism, metabolism, receptors, virus metabolism, amino acid sequence, amino acids genetics, carbohydrate sequence, chick embryo, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, molecular sequence data, species specificity, viral envelope proteins genetics.

Content, J. (1976). Cell-free translation of influenza virus mRNA. Journal of Virology 18(2): 604-18.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Cytoplasmic poly (A)-rich RNA extracted from fowl plague virus-infected cells was found to program efficiently the translation of two major peptides in the wheat germ cell-free system. These peptides have the same electrophoretic mobility, on polyacrylamide gels, as the two major virion proteins M and NP. [35S] methionine tryptic peptide analysis by one-dimensionalthin-layer ionophoresis and finger printing by two-dimensional thin-layer ionophoresis and chromatography show a high degree of similarity between the two in vitro products and the authentic viral proteins M and NP. Although virion RNA is devoid of any poly (A) sequence, it is confirmed here that the viral complementary cytoplasmic RNA contains poly (A) stretches of varying lengths. Intact purified virion was found to promote the synthesis of very low amounts of the same NP and M proteins in  this cell-free system. Quantitative aspects of data would indicate that this is due to minute amounts of complementary viral RNA associated with the virion or with the virion RNA itself. In conclusion, it is shown diectly by cell-free translation of authentic viral products that the influenza virion is "negative stranded" (Baltimore, 1971), at least for its two major structural proteins.

            Descriptors:  influenza A virus avian metabolism, RNA, messenger metabolism, RNA viral metabolism, translation, genetic, cell free system, glycoproteins biosynthesis, avian analysis, peptide synthesis, plant extracts, poly A analysis, RNA, messenger analysis, viral analysis, tissue culture, triticum, viral proteins biosynthesis.

Content, J. (1969). Virus growth inhibition by ethidium chloride and other dyes. Archiv Fur Die Gesamte Virusforschung 26(1): 74-85.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  dactinomycin pharmacology, dyes pharmacology, virus replication drug effects, acridines pharmacology, carbon isotopes, chick embryo, encephalitis viruses drug effects, encephalomyocarditis virus drug effects, fibroblasts, herpesviridae drug effects, influenza A virus avian drug effects, light, Newcastle disease virus drug effects, orotic acid metabolism, polioviruses drug effects, tissue culture, uridine metabolism, vaccinia virus drug effects.

Content, J., L.D. Wit, and M. Horisberger (1977). Cell-free coupling of influenza virus RNA transcription and translation. Journal of Virology 22(2): 247-55.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  A cell-free coupled system for the transcription and translation of fowl plague virus RNA is described. The system utilizes a new nuclease-preincubated rabbit reticulocyte lysate that has a high sensitivity to exogenous mRNA and a very low level of nuclease activity. Translation of the viral proteins in the coupled system is strictly dependent upon the viral transcriptase activity. In the coupled system the optimal concentration of magnesium is intermediate between the optimum for transcription and that for translation. Translation of the viral proteins seems faithful. The products represent the major viral peptides M and NP and two peptides with the same electrophoretic mobility as HA and P2. Viron NA is not resolved in the kind of polyacrylamide gels described. Proteins M and NP were immunoprecipitable with monospecific antisera. It is concluded that the virion-associated RNA polymerase transcribes the negative-stranded segments of the viral genome coding for these major structural proteins into fully functional mRNA's.

            Descriptors:  influenza A virus avian metabolism, RNA viral metabolism, transcription, genetic, translation, genetic, cell free system, avian enzymology, magnesium metabolism, oligonucleotides pharmacology, peptide synthesis, RNA replicase metabolism, messenger metabolism, viral biosynthesis, rabbits, reticulocytes, viral proteins biosynthesis.

Conti, G. and P. Portincasa (2002). Chromomycin A3 inhibits influenza a virus multiplication in chick embryo fibroblast cells. New Microbiologica Official Journal of the Italian Society for Medical, Odontoiatric, and Clinical Microbiology SIMMOC 25(4): 385-98.  ISSN: 1121-7138.

            NAL Call Number:  QR1.M57

            Abstract:  The multiplication of Ulster 73 virus, an avian strain of type A influenza virus, was blocked in chick embryo fibroblast cells, CEF, by treatment with 0.5 microg/ml of chromomycin A3 whereas in LLC-MK2 cells no inhibition of replication was observed. Virus-induced polypeptide synthesis in chick embryo fibroblast cells was confined to the synthesis of PB2, PB1 and PA subunits of the RNA dependent-RNA polymerase, the nucleoprotein NP, the non-structural protein NS1, the haemagglutinin HA, the non-structural protein NS2; only the membrane M1 polypeptide synthesis was greatly inhibited. Viral unpolyadenylated cRNAs synthesis was studied at a late time of the infection, 8 hours p.i.: chromomycin A3 was able to inhibit the "novo" synthesis of complementary RNA poly(A)- and segment 7 of virion RNA. The mode of action of the drug in chick embryo fibroblast cells is discussed.

            Descriptors:  chromomycin A3 pharmacology, fibroblasts drug effects, influenza A virus avian drug effects, nucleic acid synthesis inhibitors pharmacology, virus replication drug effects, cell line, chick embryo, electrophoresis, polyacrylamide gel, fibroblasts virology, avian physiology, RNA viral biosynthesis, RNA viral genetics, virus cultivation.

Conti, G., P. Portincasa, and C. Chezzi (1995). Cerulenin inhibits production of mature virion particles in chick embryo fibroblasts infected by influenza A viruses. Research in Virology 146(2): 141-9.  ISSN: 0923-2516.

            NAL Call Number:  QR355.A44

            Abstract:  We investigated acylation of haemagglutinin (HA) of type A influenza viruses during infection of permissive chick embryo fibroblasts (CEF) treated with cerulenin. Fatty acid binding was monitored using a maintenance medium containing 3H-palmitic acid. Our results suggest that fatty acid acylation of viral haemagglutinin may be essential for production of mature viral particles. Indeed, palmitoylation was found in infected CEF cells, but was lacking during the infectious cycle when cells were treated with a dose of 30 micrograms/ml of cerulenin. We discuss the possibility that acylation of virus-induced HA is a posttranslational modification regulating correct insertion of virus haemagglutinin into the cellular membrane and, as a consequence, controlling the maturation of budding influenza virus.

            Descriptors:  antiviral agents pharmacology, cerulenin pharmacology, influenza A virus avian drug effects, virion drug effects, acylation, cells,cultured, chick embryo, dose response relationship, drug, fatty acids metabolism, fibroblasts cytology, hemagglutinin glycoproteins influenza virus, hemagglutinins viral metabolism, avian metabolism, avian physiology, virus replication drug effects.

Conti, G., P. Portincasa, C. Chezzi, and A. Sanna (1988). Inhibition of late influenza virus genome expression by diamidinophenylindole. Annales De L'Institut Pasteur. Virology 139(1): 69-78.  ISSN: 0769-2617.

            NAL Call Number:  QR355.A44

            Abstract:  The growth cycle of influenza virus strain FPV, Ulster 73, was altered by treatment of LLC-MK2 cells with diamidinophenylindole. Viral protein synthesis was restricted to the early pattern of virus multiplication, and post-treatment experiments showed the ability of the drug to block virus replication until the 4th hour p.i. Drug addition (followed by removal) revealed the inhibition of synthesis of late viral products, and especially of membrane protein. Kinetic studies on the production of viral RNA indicated a decrease in the synthesis of late virus-induced RNA species, suggesting that the target of DAPI is probably the late transcription of the virus genome. The nonpermissive condition mediated by the drug could represent a suitable model to study cellular intervention during viral growth.

            Descriptors:  indoles pharmacology, influenza A virus avian growth and development, virus replication drug effects, capsid genetics, gene expression regulation drug effects, avian genetics, RNA viral biosynthesis, RNA viral genetics, time factors, viral core proteins genetics, viral nonstructural proteins.

Conti, G., P. Portincasa, A. Pesce, and C. Chezzi (1985). Biological characterization of FPV, Ulster 73, replicative cycle. Microbiologica  8(2): 151-64.  ISSN: 0391-5352.

            NAL Call Number:  QR1.M57

            Abstract:  The replication of an avian influenza A, Fowl plague virus (FPV), Ulster 73 strain, was studied in chick embryo fibroblasts, assumed to be the natural host, and in cells of different origin such as LLC-MK2, Hep-2, Vero, KB and Mc Coy. In the natural host, FPV shows a characteristic pattern of polypeptide synthesis suggesting a transcriptional and/or translational mediated control mechanism, specific for this strain of influenza A. FPV was able to give a productive infection in all the above mentioned cells releasing mature viral particles. This behaviour is very interesting if one compares FPV, Ulster strain to FPV, Rostock strain. These viruses, belonging to the same antigenic subtype (H7 N1 group) recognize the same cellular determinants but Rostock strain undergoes an abortive replication whereas Ulster strain gives productive infection in all cellular lines tested. These observations lead to postulate a viral genetic mechanism controlling host range both at early and late steps in infection. This genetic mechanism controls the interaction between viral and cell molecules affecting synthesis of virus specific polypeptides.

            Descriptors:  influenza A virus avian physiology, virus replication, chick embryo, dactinomycin pharmacology, avian genetics, RNA viral analysis, viral proteins analysis, viral proteins biosynthesis, viral structural proteins.

Conti, G., P. Valcavi, A. Natali, and G.C. Schito (1980). Different patterns of replication in influenza virus-infected KB cells. Archives of Virology 66(4): 309-20.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  When KB cells were infected either with the fowl plague (FPV) Rostock strain (Hav1N1) or the WSN (H0N1) strain of influenza A virus the yield of cell-associated haemagglutinin and neuraminidase polypeptides was essentially comparable, but virus particles were not produced in the FPV-KB system. WSN virus-infected KB cells synthesized normal amounts of mature virus particles and had all the characteristics of a permissive replication cycle. Biosynthesis and transport of RNP antigen from nucleus to cytoplasm of infected cells were traced by immunofluorescent staining at 4 and 8 hours after the beginning of infection. While the fluorescent-stained material was totally confined to the nuclei in FPV-infected KB cells, RNP antigen migrated out of the nucleus during the replicative cycle of WSN virus in the same host cell. Patterns of virus-specific protein synthesis were studied by pulse-labelling with 35S-methionine. The most significant feature concerned the amplification of synthesis of virus-induced matrix (M) protein which did not occur in FPV-infected cells but occurred normally during WSN infection. The different patterns of replication in the same host cell when infected by different influenza A viruses is discussed.

            Descriptors:  influenza A virus avian growth and development, human growth and development, cell line, cytopathogenic effect, viral, hemagglutinins viral analysis, avian metabolism, human metabolism, neuraminidase metabolism, ribonucleoproteins metabolism, viral proteins biosynthesis, virus replication.

Cook, R.F., R.J. Avery, and N.J. Dimmock (1980). Complementation with an avian influenza virus is required for synthesis of M protein of a human strain in chicken erythocytes. Archives of Virology 65(3-4): 319-24.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The M protein of avian, but not human, strains of influenza A viruses is synthesized in infected chicken erythrocytes. In dual infections an avian strain complemented the human virus and both the human and avian M proteins were expressed.

            Descriptors:  erythrocytes microbiology, influenza A virus avian metabolism, human metabolism, viral proteins biosynthesis, chick embryo, dactinomycin pharmacology, avian growth and development, human growth and development.

Cook, R.F., R.J. Avery, and N.J. Dimmock (1979). Infection of chicken erythrocytes with influenza and other viruses. Infection and Immunity 25(1): 396-402.  ISSN: 0019-9567.

            NAL Call Number:  QR1.I57

            Abstract:  Chicken erythrocytes can be infected by the fowl plague (Rostock) strain (FP/R) of influenza type A, Newcastle disease virus (NDV), and Semliki Forest virus (SFV). Only NDV and SFV produced infectious progeny, albeit at low levels. Infection by FP/R was monitored by de novo synthesis of viral proteins, and the proteins synthesized could be identified by comparison with infected chicken fibroblast cells. FP/R synthesized far greater amounts of viral protein than did NDV or SFV.

            Descriptors:  erythrocytes microbiology, chick embryo, hemagglutinins viral analysis, influenza A virus avian growth and development, avian metabolism, leukocytes microbiology, neuraminidase metabolism, Newcastle disease virus growth and development, Newcastle disease virus metabolism, Semliki Forest virus growth and development, Semliki Forest virus metabolism, viral proteins biosynthesis.

Cooper, L.A. and K. Subbarao (2000). A simple restriction fragment length polymorphism-based strategy that can distinguish the internal genes of human H1N1, H3N2, and H5N1 influenza A viruses. Journal of Clinical Microbiology 38(7): 2579-83.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  A simple molecular technique for rapid genotyping was developed to monitor the internal gene composition of currently circulating influenza A viruses. Sequence information from recent H1N1, H3N2, and H5N1 human virus isolates was used to identify conserved regions within each internal gene, and gene-specific PCR primers capable of amplifying all three virus subtypes were designed. Subtyping was based on subtype-specific restriction fragment length polymorphism (RFLP) patterns within the amplified regions. The strategy was tested in a blinded fashion using 10 control viruses of each subtype (total, 30) and was found to be very effective. Once standardized, the genotyping method was used to identify the origin of the internal genes of 51 influenza A viruses isolated from humans in Hong Kong during and immediately following the 1997-1998 H5N1 outbreak. No avian-human or H1-H3 reassortants were detected. Less than 2% (6 of 486) of the RFLP analyses were inconclusive; all were due to point mutations within a restriction site. The technique was also used to characterize the internal genes of two avian H9N2 viruses isolated from children in Hong Kong during 1999.

            Descriptors:  genes viral, influenza virology, influenza A virus human classification, human genetics, polymorphism, restriction fragment length, disease outbreaks, Hong Kong, avian classification, avian genetics, avian isolation and purification, human isolation and purification, reverse transcriptase polymerase chain reaction.

Corfield, A.P., H. Higa, J.C. Paulson, and R. Schauer (1983). The specificity of viral and bacterial sialidases for alpha(2-3)- and alpha(2-6)-linked sialic acids in glycoproteins. Biochimica Et Biophysica Acta 744(2): 121-6.  ISSN: 0006-3002.

            NAL Call Number:  381 B522

            Abstract:  The anomeric specificity of six sialidases (Vibrio cholerae, Arthrobacter ureafaciens, Clostridium perfringens, Newcastle disease virus, fowl plague virus and influenza A2 virus sialidases) was assessed with sialylated antifreeze glycoprotein, ovine submandibular gland glycoprotein and alpha 1-acid glycoprotein, resialylated specifically in alpha(2-3) or alpha(2-6) linkage with N-acetylneuraminic acid or N-glycolylneuraminic acid using highly purified sialyltransferases. The rate of release of sialic acid from these substrates was found to correlate well with the specificity observed earlier with the same sialidases using small oligosaccharide substrates, i.e., alpha(2-3) glycosidic linkages are hydrolyzed faster than alpha(2-6) linkages, with the exception of the enzyme from A. ureafaciens. Sialidase activity was higher with N-acetylneuraminic acid when compared with N-glycolylneuraminic acid. The studies also showed that the core oligosaccharide and protein structure in glycoproteins may influence the rate of release for different glycosidic linkages.

            Descriptors:  glycoproteins metabolism, neuraminidase metabolism, sialic acids metabolism, arthrobacter enzymology, Clostridium perfringens enzymology, influenza A virus avian enzymology, enzymology, Newcastle disease virus enzymology, structure activity relationship, substrate specificity, vibrio cholerae enzymology.

Corfield, A.P., M. Wember, R. Schauer, and R. Rott (1982). The specificity of viral sialidases. The use of oligosaccharide substrates to probe enzymic characteristics and strain-specific differences. European Journal of Biochemistry FEBS 124(3): 521-5.  ISSN: 0014-2956.

            NAL Call Number:  QP501.E8

            Abstract:  1. The action of sialidases from Newcastle disease virus (NDV), influenza A2 virus (IA2V) and fowl plague virus (FPV) on sialyloligosaccharide substrates containing alpha 2-3, alpha 2-6 or alpha 2-8 linkages was studied. 2. In all cases 2-3-linked sialic acids were preferentially released. Compared with II6Neu5AcLac, all 2-6-linked substrates, including sialyl-N-acetyllactosamine and its asparaginyl derivative, a urinary hexasaccharide and Neu5Ac(2-6)GalNAc were cleaved at improved rates by NDV and less by FPV sialidases. In the case of IA2V sialidase the asparaginyl oligosaccharide was very poorly cleaved, illustrating a variation in viral strain specificity. 3. A decrease in relative rates was observed in the order NDV greater than IA2V greater than FPV for substrates with 2-3 linkages relative to II6Neu5AcLac. The greatest relative rate was 470-fold higher. The 2-3-linked sialyl-N-acetyllactosaminylasparagine and IV3Neu5AcLcOse4 were poor substrates for the IA2V sialidase, but the rates were greater than with the 2-6 linked substrates. 4. The ganglioside substrate II3Neu5AcLacCer showed lower activity than its oligosaccharide analogue, but neither II3Neu5AcGgOse4Cer nor its oligosaccharide were substrates. 5. The Km values for 2-6-linked substrates were generally of the order 10 mM while those for the 2-3-linked substrates were approximately 1 mM. The V values were consistently higher for the 2-3-linked substrates. IV3Neu5AcLcOse4 showed high Km and very high V values, while the 2-8-linked disialyllactose showed this trend only with NDV enzyme, the IA2V and FPV sialidases exhibiting high Km and low V values. 6. The results are discussed in the light of the current knowledge of viral sialidase specificity and relative to the binding of virus particles to cell surfaces.

            Descriptors:  neuraminidase metabolism, oligosaccharides metabolism, viruses enzymology, colorimetry, glycoproteins metabolism, influenza A virus avian enzymology, enzymology, kinetics, Newcastle disease virus enzymology, species specificity, substrate specificity.

Cox, N.J. and R.D. Barry (1976). Hybridization studies of the relationship between influenza virus RNA and cellular DNA. Virology 69(1): 304-13.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  DNA analysis, influenza A virus avian analysis, nucleic acid hybridization, RNA, ribosomal analysis, viral analysis, bromelains pharmacology, genes, avian drug effects, avian isolation and purification, kinetics, temperature, transcription, genetic.

Crawford, J.M., M. Garcia, H. Stone, D. Swayne, R. Slemons, and M.L. Perdue (1998). Molecular characterization of the hemagglutinin gene and oral immunization with a waterfowl-origin avian influenza virus. Avian Diseases 42(3): 486-496.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Vaccination against highly pathogenic (HP) subtypes of avian influenza (AI) virus in poultry has been prohibited in the United States. Recently, policy has been changed to potentially allow use of inactivated vaccines in emergency programs to control HP H5 and H7 AI. Vaccination with inactivated virus against non-highly pathogenic AI viruses has been allowed in the U.S. turkey industry since 1979 (1) but requires expensive handling of individual birds for parenteral inoculation. Oral immunization would provide a less expensive method to protect commercial poultry from AI. Prime candidates for oral vaccines are waterfowl-origin (WFO) isolates, which have a tropism for the alimentary tract. One WFO isolate, A/mallard/Ohio/556/1987 (H5N9) (MOh87), was characterized by determining the complete nucleotide sequence of its hemagglutinin (HA) gene. The HA protein of this isolate possessed a deduced amino acid sequence nearly identical to the consensus amino acid sequence for all published H5 genes, indicating that it has potential as a broadly effective vaccine. Experimental results demonstrated measurable serum antibody responses to orally delivered live and inactivated preparations of MOh87. Oral vaccination also protected chickens from diverse, lethal H5 AI virus challenge strains and blocked cloacal shedding of challenge virus.

            Descriptors:  avian influenza virus, chickens, hemagglutinins, immunization, oral administration, genes, oral vaccination, virulence, live vaccines, inactivated vaccines, experimental infections, strain differences, nucleotide sequences, amino acid sequences, immune response, molecular sequence data, GENBANK u67783.

Crescenzo Chaigne, B., S. van der Werf, and N. Naffakh (2002). Differential effect of nucleotide substitutions in the 3' arm of the influenza A virus vRNA promoter on transcription/replication by avian and human polymerase complexes is related to the nature of PB2 amino acid 627.  Virology 303(2): 240-52.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Using a genetic system that allows the in vivo reconstitution of active ribonucleoproteins, the ability to ensure transcription/replication of a viral-like reporter RNA harboring the G(3) --> A(3), U(5) --> C(5), and C(8) --> U(8) mutations (triple 3-5-8 mutations) in the 3' arm of the promoter was examined with core proteins from human or avian strains of influenza A viruses. The efficiency of transcription/replication of the viral-like RNA with the triple 3-5-8 mutations in COS-1 cells was found to be slightly decreased as compared to the wild-type RNA when the polymerase was derived from a human virus. In contrast, it was found to be considerably increased when the polymerase was derived from an avian virus, in agreement with published observations using the avian A/FPV/Bratislava virus (G. Neumann and G. Hobom, 1995, J. Gen. Virol. 76, 1709-1717). This increase could be attributed to the compensation of the defect in transcription/replication activity in the COS-1 mammalian cell line due to the presence of a glutamic acid at PB2 residue 627, characteristic of avian strains of influenza viruses. Our results thus suggest that PB2 and/or cellular proteins interacting with PB2 could be involved in RNA conformational changes during the process of transcription/replication.

            Descriptors:  DNA directed RNA polymerases physiology, influenza A virus avian enzymology, human enzymology, promoter regions genetics, viral chemistry, transcription, genetic, viral proteins chemistry, virus replication, amino acid sequence, base sequence, cos cells, molecular sequence data, mutation, nucleic acid conformation, viral biosynthesis.

Crumpton, W.M., N.J. Dimmock, P.D. Minor, and R.J. Avery (1978). The RNAs of defective-interfering influenza virus. Virology 90(2): 370-3.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  defective viruses analysis, influenza A virus avian, RNA viral analysis, defective viruses growth and development, defective viruses metabolism, viral proteins biosynthesis.

Dammgen, J.W. and C. Scholtissek (1975). Cellular RNA and influenza-virion RNA are synthesized from different pyrimidine-nucleoside-triphosphate pools in chick-embryo cells. European Journal of Biochemistry FEBS 59(1): 51-4.  ISSN: 0014-2956.

            NAL Call Number:  QP501.E8

            Abstract:  Chick embryo cells infected with an influenza A (fowl plague) virus have been labelled with (3H)-uridine for different lengths of time. Virion RNA and cellular RNA have been separated by specific hybridization with a surplus of unlabelled viral complementary RNA and RNase digestion. The ratio of the specific radioacticity in the UMP and CMP moieties of both types of RNA has been determined. Since the rate of approach to equilibrium of CMP to UMP labelling of both types of RNA is completely different it is concluded that cellular and virion RNA are synthesized using different pyrimidine nucleoside triphosphate pools.

            Descriptors:  influenza A virus avian metabolism, pyrimidine nucleotides metabolism, RNA biosynthesis, RNA viral biosynthesis, cells cultured, chick embryo, nucleic acid hybridization, transcription, genetic, uridine metabolism.

Daniels, R.S., J.J. Skehel, and D.C. Wiley (1985). Amino acid sequences of haemagglutinins of influenza viruses of the H3 subtype isolated from horses. Journal of General Virology 66(Pt. 3): 457-64.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The amino acid sequence of the haemagglutinin of A/equine/Miami/63 (H3N8), the prototype influenza virus of the H3 subtype from horses, is deduced from the nucleotide sequence of virus RNA and compared with the sequences of haemagglutinins of viruses of this subtype isolated from humans [X-31 (H3N2)] and from birds [A/duck/Ukraine/63 (H3N8)] and with the sequence of the haemagglutinin of A/equine/Fontainebleau/79 (H3N8) a virus isolated from a recent outbreak of equine influenza. The amino acid sequence differences detected are discussed with reference to the structure of the molecules, their antigenicity and antigenic drift in influenza viruses viruses isolated from horses.

            Descriptors:  hemagglutinins viral, influenza A virus genetics, amino acid sequence, avian genetics, immunology, RNA viral genetics, species specificity, horses.

Darveau, A., N.G. Seidah, M. Chretien, and J. Lecomte (1982). Peptide mapping of 125I-labelled membrane protein of influenza viruses by reverse-phase high-performance liquid chromatography. Journal of Virological Methods 4(2): 77-85.  ISSN: 0166-0934.

            NAL Call Number:  QR355.J6

            Abstract:  The resolution potential of reverse-phase high-performance liquid chromatography (HPLC) for peptide analysis of hydrophobic viral membranes has been investigated, using as model the membrane (M) protein of influenza virus. Proteolytic digests of 125I-labelled M protein and CNBr fragments, extracted from radioiodinated whole virus, have been separated on a uBondapak C18 column with an isopropanol or acetonitrile solvent system. Peptide mapping of trypsin digests of M protein from A/PR/8/34 (H1N1) and A/chicken/Germany/N/49 (H10N7) viruses was identical, whereas Staphylococcus aureus V8 protease digests showed minor differences in at least two peptides. The results also show that HPLC is a powerful tool for the separation of proteolytic digests of viral proteins, since the peptide maps are highly reproducible and recovery was greater than 85%.

            Descriptors:  chromatography, high pressure liquid methods, influenza A virus avian analysis, membrane proteins analysis, peptides analysis, viral proteins analysis, electrophoresis, polyacrylamide gel, iodine radioisotopes.

Datema, R., P.A. Romero, R. Rott, and R.T. Schwarz (1984). On the role of oligosaccharide trimming in the maturation of Sindbis and influenza virus. Archives of Virology 81(1-2): 25-39.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The alpha-glucosidase inhibitor bromoconduritol inhibits the formation of the N-linked, complex-type oligosaccharides of the glycoproteins from influenza viruses (fowl plague virus, influenza virus PR-8) and from sindbis virus. Viral glycoproteins produced in bromoconduritol-treated chicken-embryo and baby-hamster kidney cells are fully glycosylated, but accumulate N-linked, high-mannose oligosaccharides of the composition Glc1Manx (GlcNAc)2 (x = 7, 8, and 9). Other alpha-glucosidase inhibitors (nojirimycin, deoxynojirimycin, acarbose) were not specific inhibitors of oligosaccharide processing under the conditions used in the present investigation. In bromoconduritol-treated, sindbis virus-infected chicken-embryo and baby-hamster kidney cells, the sindbis glycoproteins are metabolically stable. Specific proteolytic cleavage of the polyprotein precursors to form E2 and E1 occurs in bromoconduritol-treated chicken-embryo cells, but cleavage of PE2 to E2 is prevented in the infected baby-hamster kidney cells. Yet, release of infectious sindbis virus particles is inhibited in both cell types indicating that the formation of complex oligosaccharides is required for a late step in virus formation. The release of virus particles from influenza virus PR-8-infected bromoconduritol-treated chicken-embryo cells is not inhibited, and virus with only high-mannose oligosaccharides is formed. In contrast, when chicken-embryo cells were infected with the influenza virus fowl plague virus, release of infectious particles was inhibited. The fowl plague virus hemagglutinin is cleaved in chicken-embryo cells, in contrast to the hemagglutinin of the PR-8 virus. However, the cleavage products HA1 and HA2 do not reach the cell surface. In addition, or as a consequence, HA1 and HA2 are proteolytically broken down, whereas uncleaved hemagglutinin of PR-8 appeared metabolically stable. These results may explain the decrease in formation of fowl plague virus particles and the lack of effect on PR-8 virus in bromoconduritol-treated cells. This work thus shows different biological roles for oligosaccharide processing.

            Descriptors:  glycoproteins biosynthesis, influenza A virus avian growth and development, oligosaccharides metabolism, sindbis virus growth and development, viral proteins biosynthesis, cell line, chick embryo, glycoproteins isolation and purification, glycoside hydrolases antagonists and inhibitors, hamsters, avian drug effects, inositol analogs and derivatives, inositol pharmacology, kidney, oligosaccharides isolation and purification, sindbis virus drug effects, viral proteins isolation and purification.

Davenport, F.M., A.V. Hennessy, and E. Minuse (1968). The age distribution in humans of hemagglutinating-inhibiting antibodies reacting with avian strains of influenza A virus. Journal of Immunology 100(3): 581-5.  ISSN: 0022-1767.

            NAL Call Number:  448.8 J8232

            Descriptors:  antibodies analysis, influenza immunology, influenza A virus avian immunology, adolescent, adult, aged, aging, child, child preschool, hemagglutination inhibition tests, infant, middle aged, statistics.

Davey, J., S.M. Hurtley, and G. Warren (1985). Reconstitution of an endocytic fusion event in a cell-free system. Cell 43(3 Pt. 2): 643-52.  ISSN: 0092-8674.

            NAL Call Number:  QH573.C42

            Abstract:  Using a cell-free system we have obtained fusion of vesicles from the endocytic pathway. The fusion is rapid, efficient, and requires ATP. Only vesicles derived from certain positions along the endocytic pathway are capable of fusing. Lysosomes and vesicles derived from the plasma membrane do not fuse.

            Descriptors:  endocytosis, membrane fusion, adenosine triphosphate physiology, cell line, cell membrane physiology, cell free system, hamsters, influenza A virus avian, kidney, lysosomes physiology, mesocricetus, Semliki Forest virus, sialic acids analysis.

Davies, P. and R.D. Barry (1966). Nucleic acid of influenza virus. Nature 211(47): 384-7.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Descriptors:  orthomyxoviridae analysis, RNA viral analysis, aphthovirus analysis, centrifugation, density gradient, encephalitis viruses analysis, influenza A virus avian analysis, molecular weight, Newcastle disease virus analysis, phosphorus isotopes, rauscher virus analysis, sarcoma viruses, avian analysis, spectrum analysis.

Deibel, R., D.E. Emord, W. Dukelow, V.S. Hinshaw, and J.M. Wood (1985). Influenza viruses and paramyxoviruses in ducks in the Atlantic flyway, 1977-1983, including an H5N2 isolate related to the virulent chicken virus. Avian Diseases 29(4): 970-85.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  From 1977 to 1983, waterfowl migrating along the Atlantic flyway were annually monitored for orthomyxoviruses and paramyxoviruses in an area in central New York State. A total of 168 influenza isolates were obtained from 1,430 waterfowl. Twenty-four combinations of hemagglutinin and neuraminidase subtypes were detected, with as many as 12 found in a single year. One combination, an H5N2 isolate in 1982, was closely related to the virulent chicken virus that appeared in Pennsylvania in 1983. The prevalence of influenza varied greatly among the common waterfowl species: mallards 42%, black ducks 30%, blue-winged teal 11%, wood ducks 2%, and Canada geese 0%. A total of 89 paramyxoviruses were also from these waterfowl. In contrast to findings with influenza virus, the prevalence of paramyxoviruses did not differ significantly among the duck species. Serotype 1 (Newcastle disease virus) was predominant; three other serotypes were also identified. These findings indicated that ducks in the Atlantic flyway continually harbor influenza viruses and paramyxoviruses. The viruses may be a source of infection for other species.

            Descriptors:  ducks microbiology, influenza A virus avian isolation and purification, orthomyxoviridae isolation and purification, paramyxoviridae isolation and purification, antigens, viral analysis, demography, New York, species specificity.

Dem'ianenko, I.V., Z.I. Rovnova, E.I. Isaeva, and Z.K. Chuvakova (1989 ). Antigennaia struktura gemaggliutininov virusov grippa H1N1 (Hsw1N1), vydelennykh ot liudei i utok. [Antigenic structure of hemagglutinins of influenza H1N1 (Hsw1N1) virus isolated from humans and ducks]. Voprosy Virusologii 34(6): 661-5.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The method of specific adsorption followed by the use of antisera in HI test and competitive enzyme immunoassay was used to study the antigenic composition of hemagglutinins (HA) Hsw1 in influenza viruses isolated in 1982 from humans in Bulgaria and in 1976 in Canada from ducks as well as their antigenic relationships with HA of Hsw1 variant isolated from swine and man. Hemagglutinins of Hsw1 strains isolated from man in Bulgaria and Alma-Ata were found to be similar to HA of A/New Jersey/8/76 virus in two determinants and with hemagglutinin of the classic virus of swine in three determinants. The HA of A/duck/Alberta/35/76 virus was similar in three determinants to HA of A/New Jersey/8/76 virus and in two determinants with other Hsw1 variants. The similarities and differences in antigenic determinants of HA in Hsw1 viruses isolated from man and animals attest to their common origin and different modes of variability.

            Descriptors:  epitopes analysis, hemagglutinins viral immunology, influenza A virus avian immunology, human immunology, ducks, enzyme linked immunosorbent assay, immunosorbent techniques.

Dem'ianenko, I.V., A.A. Shilov, Z.K. Chuvakova, O.V. Chaika, and E.I. Isaeva (1988). Sravnitel'naia kharakteristika gemaggliutinov virusov grippa A s antigennoi strukturoi Hsw1N1, vydelennykh ot cheloveka i zhivotnykh. [Comparative characteristics of hemagglutinins of influenza A viruses with antigenic structure Hsw1N1 isolated from man and animals]. Voprosy Virusologii 33(2): 157-62.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Competitive radioimmunoassay was used to study the antigenic composition of hemagglutinin of Hsw1N1 viruses isolated from man in comparison with hemagglutinin Hsw1 of influenza virus of swine and ducks. The data of oligonucleotide analysis of the 4th RNA segment coding for hemagglutinin in these viruses are presented. It has been shown that in Alma-Ata, 1984-1985, influenza viruses Hsw1N1 were isolated with the antigenic structure of hemagglutinin and with the hemagglutinin gene identical with those of the classical influenza virus of swine A/Swine/Iowa/15/30 but differing from virus A/New Jersey/8/76.

            Descriptors:  antigens, viral analysis, hemagglutinins viral analysis, influenza A virus avian immunology, human immunology, influenza A virus porcine immunology, immunology, adsorption, antigens, viral genetics, binding, competitive, ducks, genes viral, hemagglutinins viral genetics, avian genetics, avian isolation and purification, human genetics, human isolation and purification, porcine genetics, porcine isolation and purification, Kazakhstan, oligonucleotides analysis, oligonucleotides genetics , RNA viral analysis,  viral genetics, radioimmunoassay methods, swine.

Desheva, J.A., L.G. Rudenko, G.I. Alexandrova, X. Lu, A.R. Rekstin, J.M. Katz, N.J. Cox, and A.I. Klimov (2004). Reassortment between avian apathogenic and human attenuated cold-adapted viruses as an approach for preparing influenza pandemic vaccines. International Congress Series 1263: 724-727.

            Abstract:  To prepare candidate influenza pandemic vaccines, we are developing an approach based on reassortment of antigenically appropriate nonpathogenic avian viruses of different subtypes (H5, H9, H7) with the cold-adapted master strain (MS) A/Leningrad/134/17/57 (Len/17) that is currently used in Russia for preparing licensed live attenuated vaccines for adults and children. In the present study, reassortants between A/Duck/Potsdam/1402-6/86(H5N2) (H5N2-wt) and Len/17 were obtained. One of the clones, A/17/Duck/Potsdam/86-92(H5N2) (Len17/H5), was chosen for further detailed genetic and antigenic analysis. Len17/H5 inherited the HA gene from the H5N2-wt and all other genes from Len/17 (7:1 genome composition). The HA gene sequence of Len17/H5 was identical to that of the parent H5N2-wt virus. The antigenic profile of the reassortant virus was similar to that of the H5N2-wt parent strain in the hemagglutination-inhibition (HI) test with a panel of antisera to different avian and human H5 viruses. The reassortant demonstrated high growth ability (9.3+0.3 lg EID50/ml) in embryonated hens' eggs (CE) at optimal (34 [deg]C) temperature, comparable with that of the parent Len/17 MS. Also, Len17/H5 demonstrated cold-adapted (ca) and temperature-sensitive (ts) phenotypes similar to those of Len/17 and was attenuated for mice.

            Descriptors:  avian influenza, live attenuated reassortant vaccine.

Deshpande, K.L., V.A. Fried, M. Ando, and R.G. Webster (1987). Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence. Proceedings of the National Academy of Sciences of the United States of America 84(1): 36-40.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Based on nucleotide sequence analysis of the hemagglutinin (HA) gene from the virulent and avirulent A/chicken/Pennsylvania/83 influenza viruses, it was previously postulated that acquisition of virulence was associated with a point mutation that resulted in loss of a glycosylation site. Since there are two potential glycosylation sites in this region of the HA molecule and since all Asn-Xaa-Thr/Ser sequences in the HAs of different strains are not necessarily glycosylated, the question remained open as to whether either one of these sites was glycosylated. We now provide direct evidence that a site-specific glycosylation affects cleavage of the influenza virus HA and thus virulence. We have identified the glycosylation sites on the HA1 subunit from the virulent and avirulent strains by direct structural analysis of the isolated proteins. Our results show that the only difference in glycosylation between the HA1s of the virulent and avirulent strains is the lack of an asparagine-linked carbohydrate on the virulent HA1 polypeptide at residue 11. Further, we show that the HA1s of both the avirulent and virulent viruses are not glycosylated at one potential site, while all other sites contain carbohydrate. Amino acid sequence analysis of the HA1 of an avirulent revertant of the virulent strain confirmed these findings.

            Descriptors:  genes, structural, genes viral, glycoproteins genetics, hemagglutinins viral genetics, influenza A virus avian pathogenicity, amino acid sequence, chick embryo, chromatography, high pressure liquid, glycopeptides analysis, hemagglutinins viral isolation and purification, avian genetics, oligosaccharides analysis, peptide fragments analysis, trypsin, virulence.

Deshpande, K.L., C.W. Naeve, and R.G. Webster (1985). The neuraminidases of the virulent and avirulent A/Chicken/Pennsylvania/83 (H5N2) influenza A viruses: sequence and antigenic analyses. Virology 147(1): 49-60.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  To define the sequence changes that occurred in an avian influenza virus neuraminidase (NA) during the evolution of virulence, we have studied the NA of the virulent and avirulent A/Chick/Penn/83 (H5N2) influenza viruses. A comparison of the deduced amino acid sequence from these viruses shows that the virulent strain, which evolved from the avirulent by the accumulation of point mutations (Bean et al., 1985), acquired four amino acid changes in the NA: one in the transmembrane segment, one in the stalk, and two in the head. A comparison of the deduced amino acid sequences with those of the human N2 NAs indicates a 20-amino acid deletion in the stalk of the Chick/Penn/83 NA. Antigenic analysis of the NAs from the avirulent and virulent Chick/Penn/83 virus shows they are antigenically very closely related, but can be distinguished with two monoclonal antibodies at a site which probably involves at least one of the amino acid changes in the NA head. Antigenic analysis also shows the Chick/Penn/83 NAs are closely related to the NAs of other N2 avian influenza viruses isolated between 1965 and 1984, supporting previous studies which indicate a relative antigenic stability of the NA among avian N2 influenza viruses. The Chick/Penn/83 NAs are the first N2 NA genes of an avian virus to be sequenced. These NAs are antigenically closely related to the 1957 human N2 NAs, and show a high degree of amino acid sequence homology with the prototype 1957 human N2 NA. These data give further support to the view that the 1957 human H2N2 viruses were at least partially derived from an avian source.

            Descriptors:  influenza A virus avian enzymology, neuraminidase isolation and purification, amino acid sequence, antibodies monoclonal diagnostic use, base sequence, chick embryo, chickens, epitopes analysis, genes structural, genes viral, avian genetics, avian pathogenicity, models molecular, neuraminidase immunology, protein conformation, species specificity, virulence.

Desselberger, U., K. Nakajima, P. Alfino, F.S. Pedersen, W.A. Haseltine, C. Hannoun, and P. Palese (1978). Biochemical evidence that "new" influenza virus strains in nature may arise by recombination (reassortment). Proceedings of the National Academy of Sciences of the United States of America 75(7): 3341-5.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Oligonucleotide analysis of two avian influenza A viruses (Hav6N2 and Hav6Nav4) isolated in nature showed identical or almost identical patterns for the corresponding M and HA genes; 24 of 25 and 13 of 13 large oligonucleotides were indistinguishable by two-dimensional gel analysis. On the other hand, remarkable differences in the oligonucleotide patterns of the remaining genes were observed. Only 2 of 11 oligonucleotide spots of the NS gene, 10 of 27 spots of the NA/NP genes, and 22 of 49 spots of the P genes were indistinguishable between the two strains. On the basis of this observation that at least two genes of these viruses are virtually identical whereas others show easily detectable differences, we conclude that the two avian strains are related to each other by a recombinational event. In addition, it was found that animals in nature can be doubly infected with influenza viruses. Both lines of evidence strongly suggest that recombination is at least one mechanism by which "new" influenza virus strains emerge in nature.

            Descriptors:  genes viral, influenza A virus avian genetics, recombination, genetic, hemagglutinins viral analysis, avian immunology, oligoribonucleotides analysis, RNA viral analysis.

Desselberger, U. and P. Palese (1978). Molecular weights of RNA segments of influenza A and B viruses. Virology 88(2): 394-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus analysis, orthomyxoviridae analysis, RNA viral analysis, genes viral, hemagglutinins viral genetics, avian analysis, human analysis, genetics, molecular weight, neuraminidase genetics, nucleic acid denaturation, oligonucleotides analysis, orthomyxoviridae genetics.

Diringer, H., W.R. Willems, and R. Rott (1978). Metabolism of myoinositol in avian and mammalian cells infected with naked and enveloped DNA and RNA viruses. Journal of General Virology 40(2): 471-4.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The uptake of 3H-inositol into the pool of free inositol and its incorporation into the lipid phosphatidylinositol have been studied in various avian and mammalian cells infected by different viruses. In all the virus-cell systems investigated, virus infection results in a drastically reduced amount of free 3H-inositol about 3 to 5 h post-infection, demonstrable in the infected cells as compared to the mock-infected controls. In contrast, the incorporation of 3H-inositol into lipid can be enhanced, reduced, or not influenced at all, depending on the virus-cell system under observation.

            Descriptors:  DNA viruses growth and development, inositol metabolism, RNA viruses growth and development, adenoviruses, human growth and development, birds, cell line, herpesvirus 1, suid growth and development, influenza A virus avian growth and development, mammals, Newcastle disease virus growth and development, phosphatidylinositols biosynthesis, polioviruses growth and development, tissue culture.

Donatelli, I., L. Campitelli, M.R. Castrucci, A. Ruggieri, L. Sidoli, and J.S. Oxford (1991). Detection of two antigenic subpopulations of A(H1N1) influenza viruses from pigs: antigenic drift or interspecies transmission? Journal of Medical Virology 34(4): 248-57.  ISSN: 0146-6615.

            Abstract:  Serological analysis of a group of 63 influenza H1N1 viruses isolated from pigs in Italy in the period 1976-1988 revealed the presence of two distinct antigenic subpopulations: some viruses possessed a haemagglutinin indistinguishable from that of viruses typically associated with pigs, i.e., A/New Jersey/8/76 (H1N1), whereas others showed a close antigenic relatedness with the haemagglutinin of avian-like H1 viruses. These findings represent further evidence that influenza A viruses from avian species may be transmitted to mammals. The surface and internal proteins of some of these viruses were also analyzed biochemically to evaluate the molecular relatedness among viruses circulating in non-human hosts.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, porcine immunology, orthomyxoviridae infections veterinary, swine microbiology, swine diseases microbiology, antibodies, monoclonal immunology, antigenic variation, electrophoresis, polyacrylamide gel, avian isolation and purification, porcine isolation and purification, Italy, orthomyxoviridae infections microbiology, orthomyxoviridae infections transmission, peptide mapping, species specificity.

Donis, R.O., W.J. Bean, Y. Kawaoka, and R.G. Webster (1989). Distinct lineages of influenza virus H4 hemagglutinin genes in different regions of the world. Virology 169(2): 408-17.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  To understand the determinants of influenza virus evolution, phylogenetic relationships were determined for nine hemagglutinin (HA) genes of the H4 subtype. These genes belong to a set of viruses isolated from several avian and mammalian species from various geographic locations around the world between 1956 and 1985. We found that the HA gene of the H4 subtype is 1738 nucleotides in length and is predicted to encode a polypeptide of 564 amino acids. The connecting peptide, which is removed from the precursor polypeptide by peptidases to yield the mature HA1 and HA2 polypeptides, contains only one basic amino acid. This type of connecting peptide is a feature of all avian avirulent HAs. On the basis of pairwise nucleotide sequence homology comparisons the genes can be segregated into two groups: influenza virus genes isolated in North America and those isolated from other parts of the world. A high degree of homology exists between pairs of genes from viruses of similar geographic origin. The nucleotide sequences within a group differ by 1.5 to 10.6%; in contrast, between groups the differences range from 15.8 to 19.4%. An evolutionary tree for the nine sequences suggests that North American isolates have diverged extensively from those circulating in other parts of the world. Geographic barriers which determine flyway outlay may prevent the gene pools from extensive mixing. The lack of correlation between date of isolation and evolutionary distance suggests that different H4 HA genes cocirculate in a fashion similar to avian H3 HA genes (H. Kida et al., 1987, Virology 159, 109-119) and influenza C genes (D. Buonagurio et al., 1985, Virology 146, 221-232) implying the absence of selective pressure by antibody that would give a significant advantage to antigenic variants. In contrast to avian influenza virus genes, human influenza virus genes evolve rapidly under the selective pressure of antibody.

            Descriptors:  hemagglutinins viral genetics, influenza A virus genetics, amino acid sequence, base sequence, cloning, molecular, geography, molecular sequence data, sequence homology, nucleic acid.

Dotti, C.G., J. Kartenbeck, and K. Simons (1993). Polarized distribution of the viral glycoproteins of vesicular stomatitis, fowl plague and Semliki Forest viruses in hippocampal neurons in culture: a light and electron microscopy study. Brain Research 610(1): 141-7.  ISSN: 0006-8993.

            Abstract:  We have shown previously using immunofluorescence microscopy that upon infection of polarized hippocampal cells in culture with vesicular stomatitis virus (VSV) and fowl plague virus (FPV) the VSV glycoprotein is delivered to the plasma membrane of the dendrites and of the cell body whereas the FPV hemagglutinin is transported to the axonal surface (Cell, 62 (1990) 63-72). In this work electron microscopy of infected rat hippocampal neurons showed that VSV progeny budded from the plasma membrane of the dendrites and the cell body. The location of the budding virions corresponded to the distribution of the VSV glycoprotein which was detected over the somatodendritic plasma membrane by immunoelectron microscopy. In contrast, no FPV formation was seen in the infected neurons although the FPV hemagglutinin was localized to the axonal surface by immunoelectron microscopy. In Semliki Forest virus (SFV) infected hippocampal cells we observed that the viral glycoproteins were exclusively present in the dendrites and cell body but not in axons.

            Descriptors:  cell polarity physiology, hippocampus microbiology, membrane glycoproteins analysis, neurons microbiology, viral envelope proteins analysis, cultured cells, hippocampus cytology, influenza A virus avian isolation and purification, microscopy, microscopy, electron, microscopy, immunoelectron, rats, rats, Sprague Dawley, Semliki Forest virus isolation and purification, vesicular stomatitis Indiana virus isolation and purification.

Dotti, C.G. and K. Simons (1990). Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell 62(1): 63-72.  ISSN: 0092-8674.

            NAL Call Number:  QH573.C42

            Abstract:  Cultured hippocampal neurons were infected with a temperature-sensitive mutant of vesicular stomatitis virus (VSV) and a wild-type strain of the avian influenza fowl plague virus (FPV). The intracellular distribution of viral glycoproteins was monitored by immunofluorescence microscopy. In mature, fully polarized neurons the VSV glycoprotein (a basolateral protein in epithelial MDCK cells) moved from the Golgi complex to the dendritic domain, whereas the hemagglutinin protein of FPV (an apically sorted protein in MDCK cells) was targeted preferentially, but not exclusively, to the axon. The VSV glycoprotein appeared in clusters on the dendritic surface, while the hemagglutinin was distributed uniformly along the axonal membrane. Based on the finding that the same viral glycoproteins are sorted in a polarized fashion in both neuronal and epithelial cells, we propose that the molecular mechanisms of surface protein sorting share common features in the two cell types.

            Descriptors:  axons microbiology, dendrites microbiology, glycoproteins analysis, hippocampus microbiology, influenza A virus avian genetics, neurons microbiology, vesicular stomatitis Indiana virus genetics, viral proteins analysis, cultured cells, embryo, fluorescent antibody technique, glycoproteins genetics, rats, viral proteins genetics.

Dragun, M., B. Rada, L. Novotny, and J. Beranek (1990). Antiviral activities of pyrimidine nucleoside analogues: some structure--activity relationships. Acta Virologica 34(4): 321-9 .  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Seventeen nucleoside derivatives (derived from arabinosylcytosine, resp. cytidine, 5-fluorouracil and uracil) were tested by agar-diffusion plaque-inhibition test for their antiviral activity with herpes simplex, vaccinia, fowl plague, Newcastle disease and western equine encephalomyelitis viruses. The highest antiviral activity against DNA viruses exhibited arabinosylcytosine, N4-acylarabinosylcytosines, arabinosylthiouracil, cyclocytidine and its 5'-chloroderivative. RNA viruses were inhibited by 5-fluorouridine only, whereas other tested compounds were ineffective or showing marginal activity only. By search for relationship between chemical structure and antiviral activity a tendency was found of higher antiviral activity at lower lipophilicity. This is probably due to better transport of the studied compounds into cell. The chemical structure, however, is the main reason of antiviral activity.

            Descriptors:  antiviral agents chemistry, pyrimidine nucleosides pharmacology, encephalitis virus, western equine drug effects, encephalitis virus, western equine growth and development, influenza A virus avian drug effects, avian growth and development, Newcastle disease virus drug effects, Newcastle disease virus growth and development, plaque assay, pyrimidine nucleosides chemistry, simplexvirus drug effects, simplexvirus growth and development, structure activity relationship, vaccinia virus drug effects,  vaccinia virus growth and development.

Drzeniek, R. and A. Gauhe (1970). Differences in substrate specificity of myxovirus neuraminidases. Biochemical and Biophysical Research Communications 38(4): 651-6.  ISSN: 0006-291X.

            NAL Call Number:  442.8 B5236

            Descriptors:  influenza A virus avian enzymology, neuraminidase, Newcastle disease virus enzymology, binding sites, chromosomes, genetic code, glycosides, kinetics, lactose, neuraminic acids, species specificity, time factors.

Duc Dodon, M., R. Cecchelli, R. Cacan, L. Gazzolo, and A. Verbert (1984). Viral neuraminidase and cellular ectosialyltransferase in human lymphoblastoid cells infected with influenza virus. Biochimie  66(6): 493-6.  ISSN: 0300-9084.

            NAL Call Number:  383 SO1

            Abstract:  In human lymphoblastoid cells, infected with an influenza virus, Fowl Plague Virus (FPV), glycoproteins (such as secreted IgM) are hyposialylated, through the action of viral neuraminidase. In this study, the modulation of the cellular ectosialyltransferase activity during viral infection was investigated. This activity was detectable in FPV-infected cells, was shown to be 2.5-fold higher than that of uninfected cells, and to be able to restore, at least partially, the level of sialylation of the cell surface acceptors.

            Descriptors:  cell transformation, viral, influenza A virus avian enzymology, neuraminidase metabolism, sialyltransferases metabolism, transferases metabolism, cell line, cell membrane metabolism, clostridium enzymology, glycoproteins metabolism, kinetics, lymphocytes, membrane proteins metabolism.

Duc Dodon, M., L. Gazzolo, G.A. Quash, and T.F. Wild (1982). Secretion of immunoglobulins by human lymphocytes after infection with influenza virus. Journal of General Virology 63(2): 441-50.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The biosynthesis of IgM by the Epstein-Barr virus-negative RAMOS lymphoblastoid cell line infected with an influenza A virus, fowl plague virus Dobson strain (FPV-B), was investigated. The results show that FPV infection of RAMOS cells slightly inhibited overall cellular protein synthesis only at 24 h after infection, despite the synthesis of FPV-specific proteins. However, even at this time, the synthesis and secretion of IgM were not affected by virus infection. Secreted IgM contained a reduced amount of sialic acid. The quantity of the asialylated IgM increased proportionally to the amount of enzymically active neuraminidase, suggesting that the asialylation of IgM is due to the action of virus neuraminidase. No such asialylated IgM was observed in RAMOS cells infected with measles virus, which does not possess neuraminidase. These results, together with a previous observation of ours that asialylated immunoglobulins acquire an altered antigenicity, suggest that the modulation of enzyme activities in B lymphocytes in response to an exogenous aggression may lead to disturbances in the structure and in the antigenic properties of immunoglobulins.

            Descriptors:  immunoglobulin m metabolism, influenza A virus avian physiology, lymphocytes microbiology, cell line, immunoglobulin m analysis, lymphocytes immunology, lymphoma, neuraminidase metabolism, proteins analysis, sialic acids analysis, virus replication.

Duhaut, S.D. and J.W. McCauley (1996). Defective RNAs inhibit the assembly of influenza virus genome segments in a segment-specific manner. Virology 216(2): 326-337.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Four avian influenza viruses have been generated, each containing a single extra defective RNA segment in addition to the eight standard segments. Three of the extra RNAs were derived from segment 1 and the fourth from segment 2. Chick embryo fibroblast cells were infected with each virus, and a wild-type virus. Virus RNA was quantified in extracts of virus-infected cells and in virus released by 10 hr postinfection using reverse transcription and by Northern blot analysis. In the case of two of the viruses the presence of the defective RNA did not markedly affect the accumulation of virus RNA within the infected cell, but significantly and selectively reduced the amount of the "parent" segment in released virus. This effect was reduced in a third virus. In a fourth virus, defective RNA was found to be present at a low-input multiplicity and results were varied. Mixed infections of one of the viruses with a closely related wild-type virus resulted in reduction of the corresponding vRNA segment of the nondefective virus. We conclude that assembly of influenza virus segments is not a purely random process.

            Descriptors:  chicks, avian influenza virus, RNA, infection, pathogenesis, quantitative analysis, fibroblasts, acids, analytical methods, birds, cells, chickens, disease transmission, domestic animals, domesticated birds, Galliformes, influenza virus, livestock, nucleic acids, nucleic compounds, organic acids, orthomyxoviridae, pathogenesis, poultry, useful animals, viruses, young animals, reverse transcription, virus assembly, transcription, mixed infections.

Durand, D.P. and R. Borland (1969). Effect of input multiplicity on infection of cells with myxoviruses as studies by hemadsorption. Proceedings of the Society for Experimental Biology and Medicine, New York, NY 130(1): 44-7.  ISSN: 0037-9727.

            NAL Call Number:  442.9 So1

            Descriptors:  orthomyxoviridae pathogenicity, serologic tests, hemadsorption inhibition tests, immune sera pharmacology, influenza A virus avian pathogenicity, methods, Newcastle disease virus pathogenicity, tissue culture.

Easterday, B., W.G. Laver, H.G. Pereira, and G.C. Schild (1969). Antigenic composition of recombinant virus strains produced from human and avian influenza A viruses. Journal of General Virology 5(1): 83-91.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  antigens analysis, neuraminidase analysis, orthomyxoviridae analysis, orthomyxoviridae immunology, recombination, genetic, electrophoresis, hemagglutination inhibition tests, hemagglutinins viral analysis, hybridization, genetic, immunodiffusion, influenza A virus avian.

Eggert, H.J., B. Brux, G. Righter, and H. Sinnecker (1984). Charakterisierung der RNS-polymerase-aktivitat hochgereinigter praparationen des influenzavirus a/duck/alberta/48/76. [Characterization of RNA polymerase activity of highly purified preparations of influenza virus A/duck/Alberta/48/76]. Zentralblatt Fur Bakteriologie, Mikrobiologie, Und Hygiene. Series A, Medical Microbiology, Infectious Diseases, Virology, Parasitology 256(4): 534-40.  ISSN: 0176-6724.

            NAL Call Number:  448.3 C33 (1)

            Abstract:  The influenza virus A/duck/Alberta/48/76 with the antigen formula H7N3 (16) and Hav1 Nav2 (WHO nomenclature from 1971) (15), respectively, as well as a nonpathogenic virus of the subtype Hav1 were purified to a high degree by ultracentrifugation in continuous sucrose gradients (15-40% w/w and 20-60% w/w, respectively). The activity of the RNA polymerase of this virus preparation was determined by incorporating 3H-UMP in acid insoluble material following preincubation of the virus with the nonionic detergens Nonidet P-40 for 15 min at 32 degrees C. The influence of different concentrations was investigated of dinucleotid, NaCl, MgCl2, Nonidet P-40 and different incubation temperatures. Optimal incorporation rates were found at following conditions: 0.2 mM dinucleotid ApG, 150 mM sodium chloride and 8 mM magnesium chloride by concentration of ions, 0.25-0.5% detergens Nonidet P-40 as well as a temperature of incubation of 32 degrees C. The data for optimal polymerase activity for the avian influenza virus A/duck/Alberta/48/76 are generally not different from the conditions described for the Fowl-Plague-Virus and for human strains.

            Descriptors:  DNA directed RNA polymerases metabolism, influenza A virus avian enzymology, bacteriological techniques, chick embryo, enzyme activation, temperature.

Ehrhardt, C., C. Kardinal, W.J. Wurzer, T. Wolff, C. von Eichel Streiber, S. Pleschka, O. Planz, and S. Ludwig (2004). Rac1 and PAK1 are upstream of IKK-epsilon and TBK-1 in the viral activation of interferon regulatory factor-3. FEBS Letters 567(2-3): 230-8.  ISSN: 0014-5793.

            NAL Call Number:  QD415.F4

            Abstract:  The anti-viral type I interferon (IFN) response is initiated by the immediate induction of IFN beta, which is mainly controlled by the IFN-regulatory factor-3 (IRF-3). The signaling pathways mediating viral IRF-3 activation are only poorly defined. We show that the Rho GTPase Rac1 is activated upon virus infection and controls IRF-3 phosphorylation and activity. Inhibition of Rac1 leads to reduced IFN beta promoter activity and to enhanced virus production. As a downstream mediator of Rac signaling towards IRF-3, we have identified the kinase p21-activated kinase (PAK1). Furthermore, both Rac1 and PAK1 regulate the recently described IRF-3 activators, I kappa B kinase- and TANK-binding kinase-1, establishing a first canonical virus-induced IRF-3 activating pathway.

            Descriptors:  DNA binding proteins metabolism, protein serine threonine kinases metabolism, transcription factors metabolism, RACL GTP binding protein metabolism, cell line, DNA binding proteins chemistry, DNA binding proteins genetics, dimerization, dogs, enzyme activation, influenza A virus, avian pathogenicity, human pathogenicity, interferon beta genetics, nuclear proteins metabolism, phosphorylation, promoter regions genetics, protein serine threonine kinases antagonists and inhibitors, protein serine threonine kinases genetics, RNA, double stranded immunology, double stranded metabolism, signal transduction, trans activators metabolism, transcription factors chemistry, transcription factors genetics, transcription, genetic, virus replication.

Ellis, M.N., C.S. Eidson, J. Brown, and S.H. Kleven (1983). Studies on interferon induction and interferon sensitivity of avian reoviruses. Avian Diseases 27(4): 927-36.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Four strains of avian reovirus were ineffective inducers of interferon (IFN) in chicken kidney (CK) cell cultures. All strains were similar in single-cycle replication curves. At multiplicities of infection between 0.20 and 10 plaque-forming units per cell, IFN was not induced in CK cells. Reovirus did not produce an IFN blocker in CK cells. Attenuated reovirus did induce IFN in aged chicken embryo fibroblast (CEF) cell cultures. By priming cells with a low dose of IFN before infection with reovirus, IFN formation by CEF could be enhanced. Ultraviolet-inactivated avian reovirus was an effective inducer of IFN in both CK and CEK cell cultures. The sensitivity of avian reoviruses (Fahey-Crawley, Reo-25, S-1133, Reo-V) to chicken interferon (Ch-IFN) was studied by the plaque-reduction method. Avian reoviruses were less sensitive to Ch-IFN than was vesicular stomatitis virus or Semliki Forest virus and appeared to be as resistant to IFN as was Newcastle disease virus.

            Descriptors:  interferons biosynthesis, reoviridae growth and development, virus replication, cultured cells, chickens, cytopathogenic effect, viral, drug resistance, microbial, influenza A virus avian growth and development, interferons pharmacology, kidney, Newcastle disease virus growth and development, Semliki Forest virus growth and development, ultraviolet rays, vesicular stomatitis Indiana virus growth and development.

Emtage, J.S., G.H. Catlin, and N.H. Carey (1979). Polyadenylation and reverse transcription of influenza viral RNA. Nucleic Acids Research 6(4): 1221-39.  ISSN: 0305-1048.

            NAL Call Number:  QD341.A2N8

            Abstract:  The polyadenylation of Fowl Plague Viral RNA and of Influenza A/Victoria Viral RNA using E. coli poly (A) polymerase and the subsequent reverse transcription of the polyadenylated species is reported. We have shown that all 8 genome fragments are adenylated and that an average of 25--30 adenylic acid residues per molecule is sufficient for maximal transcription with reverse transcriptase. The cDNA product is 95% sensitive to Sl-nuclease and hybridisation analysis against viral RNA reveals it to be a faithful copy of the RNA. Amongst the transcription products are long, discrete copies of genes 1--8, the lengths of which are comparable with those of the vRNA determined by electrophoresis on formamide acrylamide gels. These single-stranded cDNAs have been further transcribed to form double-stranded products with hair-pin structures at one end. Analysis of this material on native acrylamide gels revealed some DNA bands corresponding to the predicted sizes for genes 4--8.

            Descriptors:  Escherichia coli enzymology, nucleotidyltransferases metabolism, poly A biosynthesis, polynucleotide adenylyltransferase metabolism, RNA viral metabolism, RNA directed DNA polymerase metabolism, DNA, viral biosynthesis, influenza A virus avian, kinetics, molecular weight, nucleic acid hybridization, orthomyxoviridae.

Emtage, J.S., W.C. Tacon, G.H. Catlin, B. Jenkins, A.G. Porter, and N.H. Carey (1980). Influenza antigenic determinants are expressed from haemagglutinin genes cloned in Escherichia coli. Nature 283(5743): 171-4.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Abstract:  A gene sequence for the fowl plague virus (FPV) haemagglutinin molecule has been inserted into a bacterial plasmid such that its transcription is under the control of a promoter derived from the tryptophan operon. Such plasmids direct the synthesis of a protein that reacts specifically with antisera to FPV haemagglutinin. Evidence is also presented that in some cases DNA inserted at the HindIII site of pBR322 is expressed.

            Descriptors:  antigens, viral genetics, DNA, recombinant, Escherichia coli genetics, hemagglutinins viral genetics, influenza A virus avian genetics, epitopes, genes, structural, influenza A virus avian immunology, operon, plasmids, transcription, genetic, tryptophan genetics.

Emtage, J.S., W.C. Tacon, G.H. Catlin, B. Jenkins, A.G. Porter, and N.H. Carey (1992). Influenza antigenic determinants are expressed from haemagglutinin genes cloned in Escherichia coli. 1980. Biotechnology 24: 491-4.  ISSN: 0740-7378.

            NAL Call Number:  QD320.B56

            Descriptors:  antigens, viral biosynthesis, hemagglutinins viral biosynthesis, influenza A virus avian genetics, amino acid sequence, antigens, viral genetics, antigens, viral immunology, base sequence, Escherichia coli genetics, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, hemagglutinins viral immunology, history of medicine, 20th century, influenza A virus avian immunology, molecular sequence data, recombinant proteins biosynthesis, recombinant proteins genetics, recombinant proteins immunology.

Erokhina, L.M., N.I. Arkhipov, N.A. Lagutkin, M.M. Zubairov, N.I. Mitin, and VP Shishkov (ed.). (1980). Morfologicheskaya otsenka xhimioterapevticheskogo deistviya Midantana i preparata C-4. [Morphological assessment of the chemotherapeutic activity of the antiviral agents Midantan and C-4 (amantadine-1-boradamantine) in avian influenza]. In: Patomorfologiya, patogenez i diagnostika boleznei s. kh. zhivotnykh, Nauchnye Trudy VASKNIL, p. 168-169.

            NAL Call Number: SF769.P36

            Descriptors: avian influenza virus, chemotherapy, antiviral agents.

Ershov, F.I. and A.S. Agabalian (1970). Prostoi bystryi metod titrovaniia interferona po podavleniiu sinteza gemaggliutininov. [Simple and rapid method of interferon titration by suppression of hemagglutinin synthesis]. Laboratornoe Delo 4: 228-31.  ISSN: 0023-6748.

            Descriptors:  antibody formation, interferons analysis, arboviruses, chick embryo, encephalitis viruses, encephalomyelitis, equine, hemagglutination inhibition tests, hemagglutinins viral biosynthesis, hemolytic plaque technique, influenza A virus avian, tissue culture.

Esievo, K.A. (1983). Trypanosoma vivax, stock V953: inhibitory effect of type A influenza virus anti-HAV8 serum on in vitro neuraminidase (sialidase) activity. Journal of Parasitology 69(3): 491-5.  ISSN: 0022-3395.

            NAL Call Number:  448.8 J824

            Abstract:  Trypanosoma vivax stock V953 lysates were observed to produce neuraminidase (sialidase EC 3.2.1.18) in vitro, which cleaved neuraminic (sialic) acid from the substrate fetuin. The neuraminidase activity was proportional to the number of trypanosomes in the lysates, with 0.44, 0.88, and 1.75 X 10(6) trypanosomes producing 1.4 +/- 0.06, 3.1 +/- 0.1, and 6.7 +/- 0.1 micrograms of sialic acid liberated, respectively. Equal numbers of unlysed and lysed trypanosomes produced approximately the same amount of the enzyme. Trypanosome eluates stored at room temperature appeared to have lost neuraminidase activities within 4 days. An inhibition test for identifying the neuraminidase antigen on influenza viruses was performed in vitro on the T. vivax lysates. The inhibition test, using Type A influenza virus anti-HAV8 serum, showed a highly significant (P less than 0.0001) reduction in neuraminidase activities. The effect of equal amounts of influenza antiserum on serially diluted trypanosome lysates showed that 1 ml of influenza anti-HAV8 serum would inhibit a mean of 6.74 +/- 0.18 micrograms of T. vivax stock V953 neuraminidase activity.

            Descriptors:  antibodies, viral immunology, influenza A virus avian immunology, neuraminidase antagonists and inhibitors, Trypanosoma enzymology, immune sera, neuraminidase immunology, temperature.

Ewasyshyn, M.E. and L.R. Sabina (1983). Effects of influenza virus replication on neutral proteolytic activities in embryonated egg fluids. Acta Virologica 27(3): 193-9.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The levels of neutral protease activity associated with allantoic and amniotic fluids of embryonated eggs during the replication of influenza strains A/PR/8/34 (H1N1) and A/turkey/Ontario/7732/66 (H5N9) were investigated. A sensitive fluorometric technique proved useful for characterization and monitoring changes of protease activities in egg fluids. The predominant type of protease in allantoic and amniotic fluids had trypsin-like specificities. Variation in protease levels of both fluids occurred throughout the course of virus replication irrespective of the virus strain or the route of inoculation used. Concomitant with the production of high levels of infectious virus there was a marked decrease in neutral protease activity in the fluid from the cavity initially infected. Translocation of virus also occurred especially with amniotically infected eggs, as evidenced by high infectious virus titers and decreased protease activities in allantoic fluids.

            Descriptors:  allantois enzymology, amniotic fluid enzymology, fetal membranes enzymology, influenza A virus physiology, peptide hydrolases metabolism, virus replication, allantois microbiology, amniotic fluid microbiology, chick embryo, influenza A virus avian physiology, protease inhibitors pharmacology, turkeys.

Fang, R., W. Min Jou, D. Huylebroeck, R. Devos, and W. Fiers (1981). Complete structure of A/duck/Ukraine/63 influenza hemagglutinin gene: animal virus as progenitor of human H3 Hong Kong 1968 influenza hemagglutinin. Cell 25(2): 315-23.  ISSN: 0092-8674.

            NAL Call Number:  QH573.C42

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, influenza A virus human genetics, amino acid sequence, base sequence, cloning, molecular, ducks microbiology, epitopes, hemagglutinins viral immunology, influenza A virus avian immunology, influenza A virus human immunology, mutation.

Fatunmbi, O.O., J.A. Newman, D.A. Halvorson, and V. Sivanandan (1993). Effect of temperature on the stability of avian influenza virus antigens under different storage conditions. Avian Diseases 37(3): 639-646.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The combined effect of time and temperature on the stability of two avian influenza virus (AIV) isolates concentrated with polyethylene glycol (PEG), stored at different temperatures, and used in the preparation of avian influenza vaccine was evaluated in turkeys at 24 hr and at 12, 24, 30, 36, and 42 months of storage. The differences detected between antibodies raised in turkeys by vaccines made from isolates under different storage conditions, times, and temperatures were not significant (P > 0.05), especially with vaccines prepared from one isolate. Virus recovery rates following challenge studies of vaccinated birds were similar. However, birds that were vaccinated twice had lower rates of virus recovery from the trachea, lungs, pancreas, and fecal samples following challenge infection. The results suggest that if stable isolates of AIV can be identified, such isolates can be rapidly concentrated with PEG and stored at -20 C or -196 C for at least 42 months without any loss of potency in the vaccine prepared from these isolates. This would reduce the costs associated with vaccine storage and subsequent expiration dates.

            Descriptors:  turkeys, avian influenza virus, antigens, vaccines, freezing, storage, temperature, time, alcohols, polyethylene, vaccination, birds, disease control, Galliformes, immunization, immunological factors, immunology, immunostimulation, immunotherapy, influenza virus, polymers, processing, therapy, viruses, viral antigens, potency, polyethylene glycol.

Fedorova, G.I., R.I.A. Podcherniaeva, A.M. Amchenkova, N.I. Nikitina, and V.K. Blinova (1974). Izuchenie vzaimodeistviia virusov pozvonochnykh i virusov iadernogo poliedroza nasekomykh s peresevaemymi diploidnymi embrional'nymi kletkami drozofily [Interaction of vertebrate viruses and insect nuclear polyhedrosis viruses with transplantable diploid embryonal Drosophila cells]. TSitologiia i Genetika 8(5): 396-9.  ISSN: 0564-3783.

            NAL Call Number:  QH573.T75

            Abstract:  When the Drosophila cells were infected with the mixo- and arboviruses, in case of influenza A/WSN virus a rise in the titre and slight cytopathogenic effect with the subsequent decrease in the titre was observed. Since the decrease in the virus titer was not observed when actinomycin D was added, it was supposed that interferonlike inhibitor may be produced by the infected cells. Vacuolization and increase in the size of the infected cells were caused by all the nuclear polyhedrosis viruses tested. The number of the infected cells depended on the virus type and multiplicity of the infection.

            Descriptors:  insect viruses, viruses, arboviruses, cultured cells, cytopathogenic effect, viral, encephalitis virus, western equine, influenza A virus avian, Newcastle disease virus, orthomyxoviridae.

Feldmann, A., M.K. Schafer, W. Garten, and H.D. Klenk (2000). Targeted infection of endothelial cells by avian influenza virus A/FPV/Rostock/34 (H7N1) in chicken embryos. Journal of Virology 74(17): 8018-27.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The tissue tropism and spread of infection of the highly pathogenic avian influenza virus A/FPV/Rostock/34 (H7N1) (FPV) were analyzed in 11-day-old chicken embryos. As shown by in situ hybridization, the virus caused generalized infection that was strictly confined to endothelial cells in all organs. Studies with reassortants of FPV and the apathogenic avian strain A/chick/Germany/N/49 (H10N7) revealed that endotheliotropism was linked to FPV hemagglutinin (HA). To further analyze the factors determining endotheliotropism, the HA-activating protease furin was cloned from chicken tissue. Ubiquitous expression of furin and other proprotein convertases in the chick embryo indicated that proteolytic activation of HA was not responsible for restriction of infection to the endothelium. To determine the expression of virus receptors in embryonic tissues, histochemical analysis of alpha2,3- and alpha2,6-linked neuraminic acid was carried out by lectin-binding assays. These receptors were found on endothelial cells and on several epithelial cells, but not on tissues surrounding endothelia. Finally, we analyzed the polarity of virus maturation in endothelial cells. Studies on cultured human endothelial cells employing confocal laser scanning microscopy revealed that HA is specifically targeted to the apical surface of these cells, and electron microscopy of embryonic tissues showed that virus maturation occurs also at the luminar side. Taken together, these observations indicate that endotheliotropism of FPV in the chicken embryo is determined, on one hand, by the high cleavability of HA, which mediates virus entry into the vascular system, and, on the other hand, by restricted receptor expression and polar budding, which prevent spread of infection into tissues surrounding endothelia.

            Descriptors:  endothelium virology, influenza A virus avian pathogenicity, chick embryo, endothelium metabolism, endothelium pathology, Furin, hemagglutinin glycoproteins, influenza virus metabolism, in situ hybridization, influenza A virus avian ultrastructure, microscopy, confocal, neuraminic acids analysis, neuraminidase metabolism, organ specificity, proprotein convertase 5, receptors, virus analysis, serine endopeptidases metabolism, subtilisins metabolism.

Feldmann, H., E. Kretzschmar, B. Klingeborn, R. Rott, H.D. Klenk, and W. Garten (1988). The structure of serotype H10 hemagglutinin of influenza A virus: comparison of an apathogenic avian and a mammalian strain pathogenic for mink. Virology 165(2): 428-37.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The primary structure of the hemagglutinin of the apathogenic avian influenza virus A/chick/Germany/N/49 (H10N7) and of the serologically related strain A/mink/Sweden/84 (H10N4) pathogenic for mink has been elucidated by nucleotide sequence analysis, and the carbohydrates attached to the polypeptide have been determined. The H10 hemagglutinin has 65, 52, 46, 45, and 44% amino acid sequence homology with serotypes H7, H3, H1, H2, and H5, respectively. H10 and H7 hemagglutinins are also most closely related in their glycosylation patterns. There is a high sequence homology between both H10 strains supporting the concept that the mink virus has obtained its hemagglutinin from an avian strain. The sequence homology includes the cleavage site which consists of a single arginine as is the case with most other hemagglutinins exhibiting low susceptibility to proteolytic activation. The similarity in hemagglutinin structure between both H10 strains is discussed in light of the distinct differences in the pathogenicity of both viruses.

            Descriptors:  hemagglutinins viral genetics, influenza A virus genetics, amino acid sequence, base sequence, carbohydrates analysis, chickens microbiology, glycosylation, hemagglutinins viral analysis, influenza A virus immunology, mink microbiology, molecular sequence data, sequence homology, nucleic acid.

Finskaia, N.N., I.U.A. Smirnov, I.A. Rudneva, and N.V. Kaverin (1988). Svoistva reassortantov virusov grippa cheloveka i ptits. Reproduktsiia v kletkakh MDCK pri suboptimal'noi temperature. [Properties of reassortants of human and avian influenza viruses. Reproduction in MDCK cells at suboptimum temperatures]. Molekuliarnaia Genetika, Mikrobiologiia i Virusologiia (4): 26-9.  ISSN: 0208-0613.

            NAL Call Number:  QH506.M65F2

            Abstract:  A series of reassortants has been constructed by crossing of UV-inactivated avian influenza virus of H3N8 subtype and live human influenza virus of H1N1 subtype, adapted to growth in continuous canine kidney cell line (MDCK). The analysis of RNA duplexes has shown that the reassortants contain HA gene of avian influenza virus whereas the other genes belong to human parent virus. The reassortants were efficiently reproduced in MDCK cells at low temperature (limiting for the avian parent virus). The data suggest that the avian virus HA gene does not hamper the reproduction of reassortant viruses in mammalian cells under the conditions unfavorable for the multiplication of avian influenza subtype H3N8 viruses.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, virus replication, cultured cells, dogs, hemagglutinins viral genetics, hemagglutinins viral immunology, avian immunology, avian physiology, human immunology, human physiology, kidney, nucleic acid hybridization, phenotype, RNA viral genetics, temperature.

Fischer, A.A., K. Muller, and C. Scholtissek (1990). Specific inhibition of the synthesis of influenza virus late proteins and stimulation of early, M2, and NS2 protein synthesis by 3-deazaadenosine. Virology 177(2): 523-31.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  3-Deazaaristeromycin and 3-deazaadenosine (3DA-Ado) both interfere with the methylation of RNA, but only 3DA-Ado is metabolized to the corresponding homocysteine derivative. In contrast to 3-deazaaristeromycin, 3DA-Ado inhibits the synthesis of late influenza A virus proteins in chicken embryo cells (CEC), while it causes an overproduction of early proteins and of the nonstructural proteins NS2 and M2. Only the former effect of 3DA-Ado can be reversed by concomitant addition of adenosine, but not by guanosine. 3DA-Ado acts only early in the infectious cycle and, after removal of the drug, its effect on the yield of infectious virus is reversible. It can be significantly enhanced by homocysteine thiolactone. Except for the M gene, synthesis of viral mRNA is not significantly affected by 3DA-Ado. We conclude that 3DA-Ado acts via its homocysteine derivative by interfering with a specific post-transcriptional modification of viral mRNA and on splicing of specifically the M mRNA. In L-cells influenza viral protein synthesis is comparable to that in CEC in the presence of 3DA-Ado in that there is only little HA and M1 synthesized, and a severe overproduction of NS2 is observed. Under the experimental conditions 3DA-Ado has no inhibiting effect on the replication of other RNA viruses like Newcastle disease virus, Semliki Forest virus, or West Nile virus whose RNA is not methylated, since they do not have a nuclear phase during replication.

            Descriptors:  anti bacterial agents pharmacology, influenza A virus genetics, tubercidin pharmacology, viral proteins biosynthesis, adenosine analogs and derivatives, adenosine pharmacology, aminoglycosides, capsid biosynthesis, cell line, cultured cells, chick embryo, enzyme inhibitors pharmacology, influenza A virus avian drug effects, avian physiology, influenza A virus drug effects, influenza A virus metabolism, isomerism, kinetics, mice, RNA, messenger biosynthesis, RNA viral biosynthesis, viral core proteins biosynthesis, viral nonstructural proteins, viral proteins isolation and purification, virus replication.

Fiszon, B. and C. Hannoun (1990). Comparison of neuraminidases of the same subtype but from different species using a new method of titration. Journal of Virological Methods 27(1): 79-90.  ISSN: 0166-0934.

            NAL Call Number:  QR355.J6

            Abstract:  Neuraminidase is one of the two surface glycoproteins of influenza virions. In order to compare neuraminidases of the same subtype but isolated from different species (man, birds, pig), a new and simple method was adapted and optimized using peanut hemagglutinin. Results were very similar to those obtained with the classical method recommended by the WHO, using fetuin as a substrate. The technique was used to examine the relationship between animal and human neuraminidases belonging to serotypes N1 and N2. The results confirm the possible role of ducks as a reservoir for influenza viruses and the eventuality of interspecific exchanges.

            Descriptors:  neuraminidase analysis, orthomyxoviridae enzymology, antigenic variation immunology, ducks, influenza A virus avian classification, avian enzymology, human classification, human enzymology, porcine classification, porcine enzymology, lectins, neuraminidase immunology, orthomyxoviridae classification, peanut agglutinin, species specificity, swine.

Fiszon, B., C. Hannoun, A. Garcia Sastre, E. Villar, and J.A. Cabezas (1989). Comparison of biological and physical properties of human and animal A(H1N1) influenza viruses. Research in Virology 140(5): 395-404.  ISSN: 0923-2516.

            NAL Call Number:  QR355.A44

            Abstract:  The study of biological properties of influenza virus strains belonging to the same subtype A(H1N1) and closely antigenically related, but isolated from different animal species (man, pig and duck), demonstrated that avian strains were more resistant than those isolated from mammals to high temperature and low pH, as shown by titration of residual infectivity in cell cultures (MDCK) and by sialidase assay. The difference in behaviour could be correlated to biological adaptation of the virus to its host. Avian body temperature is 40 degrees C and influenza virus, in ducks, is enterotropic and therefore capable of passing through the low pH values in the upper digestive tract of the animal. These results do not contradict the hypothesis of a possible filiation between avian and mammalian orthomyxoviruses.

            Descriptors:  influenza A virus physiology, body temperature, cell line, ducks, hemagglutination tests, hydrogen-ion concentration, influenza A virus avian enzymology, avian growth and development, avian physiology, human enzymology, human growth and development, human physiology, porcine enzymology, porcine growth and development, porcine physiology, influenza A virus enzymology, influenza A virus growth and development, neuraminidase analysis, plaque assay, swine, temperature, virus replication.

Flehmig, B., A. Vallbracht, and H.J. Gerth (1976). Influenza virus: association of mouse-lung virulence with plaque formation in mouse kidney cells. InterVirology 7(4-5): 201-10.  ISSN: 0300-5526.

            NAL Call Number:  QR355.I5

            Abstract:  In genetic recombination experiments with the mouse-lung-adapted human influenza A/Engl/1/61 (H2N2) and an avian influenza strain A/Rostock/34 (FPV) (Hav1N1) which is avirulent for the mouse lung, recombinants in which hemagglutinin and neuraminidase were either segregated (Hav1N2; H2N1) or not segregated (Hav1N1) were selected. The recombinants were studied for mouse-lung virulence and their ability to propagate in mouse kidney cells, mouse embryo fibroblasts, chick embryo kidney cells and chick embryo fibroblasts. An association between plaque formation in mouse kidney cells and mouse-lung virulence was found.

            Descriptors:  influenza A virus human pathogenicity, antigens, viral analysis, hemagglutinins viral analysis, human growth and development, human immunology, lung microbiology, mice, neuraminidase immunology, plaque assay, recombination, genetic, tissue culture, virulence, virus replication.

Follett, E.A., C.R. Pringle, W.H. Wunner, and J.J. Skehel (1974). Virus replication in enucleate cells: vesicular stomatitis virus and influenza virus. Journal of Virology 13(2): 394-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  cultured cells microbiology, orthomyxoviridae growth and development, vesicular stomatitis Indiana virus growth and development, virus replication, autoradiography, carbon radioisotopes, cell line, cell nucleus microbiology, cytochalasin B pharmacology, electrophoresis, polyacrylamide gel, haplorhini, influenza A virus avian growth and development, avian metabolism, kidney, orthomyxoviridae metabolism, peptide synthesis, plaque assay, RNA viral biosynthesis, sulfur radioisotopes, tritium, vesicular stomatitis Indiana virus metabolism, viral proteins biosynthesis.

Fontaine, M. and M. Aymard Henry (1975). Contribution a l'etude antigenique des virus influenza des animaux. I. Neuraminidase des virus influenza equins. [Contribution to the antigenic study of influenza viruses in animals. I. Neuraminidase of the equine influenza viruses (author's transl)]. Annales De Recherches Veterinaires Annals of Veterinary Research 6(4):  397-410.  ISSN: 0003-4193.

            NAL Call Number:  SF602.A5

            Abstract:  From the Revised Nomenclature of WHO, the fowl influenza virus A/Duck/Ukraine/63 (Hav7 Neq2) has the same neuraminidase as the equine virus A/equi 2/Miami/63 (Heq2 Neq2); the A/Chicken Germany "N"/49 virus has the same neuraminidase as the equine virus A/equi 1/Prague/56. A comparative study of the antigenic specificities confirms that the Neq2 neuraminidases are closely connected, whatever their animal origin, and that the fowl strain Hav7 Neq2 can be used for the titration of anti Neq2 antibodies in the serums of animals immunized with the equine virus Heq2 Neq2. The Neqi neuraminidases of various animal origins are connected, but the neuraminidase of the fowl strain Hav2 Neqi is slightly inhibited by the anti Neq1 antibodies of animals immunized with the Heq1 Neq1 virus: to titrate the anti Neq1 antibodies of equine origin, the H72 Neq1 recombinant should therefore be used. The antigenic characterization of the different equine influenza strains isolated since 1967 by the study of their neuraminidase has been completed: The various neuraminidases, like the hemagglutinins of the various strains belonging to the sub-type A equi2 are closely connected; a minor antigenic variation, concerning the two surface antigens, seems to exist between the strain A equi 1/Prague/56 and the strain of the same subtype isolated in 1973.

            Descriptors:  antigens, viral, neuraminidase immunology, orthomyxoviridae immunology, cross reactions, epitopes, hemagglutination inhibition tests, horse diseases immunology, horses, influenza immunology, influenza veterinary, influenza A virus avian immunology.

Freidlin, P.J., R. Bock, A. Inbar, and Y. Samberg (1985). Immunoelectrophoresis of avian viral proteins in a phosphate-buffered system. Avian Diseases 29(3): 613-6.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Avian influenza and hemorrhagic enteritis viral preparations were immunoelectrophoresed in a phosphate-buffered system. Excellent separation and resolution of viral proteins were achieved. Reasons are given why this method might be preferred over the conventional method employing a veronal (barbital)-buffered system.

            Descriptors:  antigens, viral analysis, coronaviridae analysis, coronavirus, turkey analysis, influenza A virus avian analysis, viral proteins analysis, coronavirus, turkey immunology, immunoelectrophoresis methods, viral proteins immunology.

Friebolin, H., W. Baumann, G. Keilich, D. Ziegler, R. Brossmer, and H. von Nicolai (1981). 1H-NMR-Spektroskopie--Eine aussagekraftige Methode zur Bestimmung der Substratspezifitat von Sialidasen. [1H-NMR spectroscopy--a potent method for the determination of substrate specificity of sialidases (author's transl)]. Hoppe Seyler's Zeitschrift Fur Physiologische Chemie 362(11): 1455-63.  ISSN: 0018-4888.

            NAL Call Number:  384 Z38

            Abstract:  We describe here the application of 1H-NMR spectroscopy to determine the substrate specificity of sialidases using a 1:1 mixture of NeuAc alpha 2-3Gal beta 1-4Glc and NeuAc alpha 2-6Gal beta 1-4Glc, one viral and five bacterial sialidases. This method utilizes the separate signals in NMR spectra, characteristic for the different alpha ketosidically linked NeuAc residues and also for bound and free NeuAc. The signals generally most suitable for these purposes are those of H3a, H3e and NCOCH3. By observation and integration of these signals we can follow--qualitatively and quantitatively--which and how many NeuAc residues of the substrates are hydrolized. In contrast to the generally used colorimetric tests it is now possible to investigate with this method substrates containing two or more NeuAc residues and to determine the corresponding rate constants for hydrolysis of the differently bound NeuAc molecules. The six sialidases used show large differences in their specificity as compared with our "model substrate": The sialidase from fowl plague virus hydrolizes NeuAc alpha 2-3Gal beta 1-4Glc nearly 18 times and the enzyme from Clostridium perfringens four times, from Vibrio cholerae two times faster than NeuAc alpha 2-6Gal beta 1-4Glc. On the contrary, the sialidase from Arthrobacter ureafaciens hydrolizes the alpha 2-6 linkage six times faster than the alpha 2-3 linkage. The sialidases from Bifidobacterium show no obvious differences in their specificities relative to the linkage.

            Descriptors:  neuraminidase metabolism, actinomycetaceae enzymology, arthrobacter enzymology, Clostridium perfringens enzymology, influenza A virus avian enzymology, kinetics, magnetic resonance spectroscopy methods, substrate specificity, Vibrio cholerae enzymology.

Frischholz, K.W. and C. Scholtissek (1984).  Influence of infection with an influenza A virus (fowl plague) on Ca++-uptake and lipid metabolism of chick embryo cells in culture. Archives of Virology 80(2-3): 163-70.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  After infection of primary chick embryo cells with an influenza A virus (FPV) the synthesis of polar lipids was specifically inhibited, while mono-, di- and triacylglycerols and fatty acids accumulated. Influx of Ca++ accelerated and Ca++ accumulated in the infected cells. Since enzymes like choline phosphotransferase are sensitive to high concentrations of Ca++, specific inhibition of the synthesis of polar lipids is presumably due to an increased influx of Ca++ by the infection.

            Descriptors:  calcium metabolism, fowl plague metabolism, lipids metabolism, biological transport, cultured cells, chick embryo, influenza A virus avian.

Fukushi, H., R. Yanagawa, and H. Kida (1982). Host species-related antigenic groups of avian influenza viruses possessing H4 hemagglutinin revealed by monoclonal antibodies. Archives of Virology 72(3): 217-21.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, antibodies, monoclonal immunology, antibodies, viral immunology, birds microbiology, cross reactions, ducks microbiology, epitopes, hemagglutination inhibition tests, hemagglutinins viral classification, influenza A virus avian classification.

Fuller, S.D., C.H. von Bonsdorff, and K. Simons (1985). Cell surface influenza haemagglutinin can mediate infection by other animal viruses. EMBO Journal 4(10): 2475-85.  ISSN: 0261-4189.

            NAL Call Number:  QH506.E46

            Abstract:  We have used filter-grown Madin-Darby canine kidney (MDCK) cells to explore the mechanism by which influenza virus facilitates secondary virus infection. Vesicular stomatitis virus (VSV) and Semliki Forest virus (SFV) infect only through the basolateral surface of these polarized epithelial cells and not through the apical surface. Prior infection with influenza virus rendered the cell susceptible to infection by VSV or SFV through either surface. The presence of both a permissive and a restrictive surface for virus entry in the same cell allowed us to determine how the influenza infection enhanced the subsequent infection of a second virus. Biochemical and morphological evidence showed that influenza haemagglutinin on the apical surface serves as a receptor for the superinfecting virus by binding to its sialic acid-bearing envelope proteins. Influenza virus also facilitates secondary virus infection in non-epithelial cells; baby hamster kidney cells (BHK-21), which are normally resistant to infection by the coronavirus (mouse hepatitis virus MHV-A59), could be infected via the haemagglutinin-sialic acid interaction. Facilitation of secondary virus infection requires only the sialic acid-binding properties of the haemagglutinin since the uncleaved haemagglutinin could also mediate virus entry.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian metabolism, receptors, virus metabolism, vesicular stomatitis Indiana virus metabolism, cell compartmentation, cultured cells, dogs, endocytosis, hamsters, kidney microbiology, murine hepatitis virus metabolism, Semliki Forest virus metabolism, sialic acids physiology, viral proteins biosynthesis, virus replication.

Fynan, E.F., R.G. Webster, D.H. Fuller, J.R. Haynes, J.C. Santoro, and H.L. Robinson (1993). DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proceedings of the National Academy of Sciences of the United States of America 90(24): 11478-82.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials using two inoculations of from 50 to 300 micrograms of purified DNA in saline, 67-95% of test mice and 25-63% of test chickens have been protected against a lethal influenza challenge. Parenteral routes of inoculation that achieved good protection included intramuscular and intravenous injections. Successful mucosal routes of vaccination included DNA drops administered to the nares or trachea. By far the most efficient DNA immunizations were achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis. In mice, 95% protection was achieved by two immunizations with beads loaded with as little as 0.4 micrograms of DNA. The breadth of routes supporting successful DNA immunizations, coupled with the very small amounts of DNA required for gene-gun immunizations, highlight the potential of this remarkably simple technique for the development of subunit vaccines.

            Descriptors:  DNA, viral administration and dosage, fowl plague prevention and control, hemagglutinins viral genetics, influenza prevention and control, influenza A virus avian immunology, human immunology, cell line, chickens, DNA, viral immunology, fowl plague immunology,  genes viral, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral biosynthesis, influenza immunology, avian genetics, human genetics, injections, injections, intramuscular, injections, intravenous, mice, mice inbred BALB c, mucous membrane, restriction mapping, transfection, viral envelope proteins biosynthesis, viral envelope proteins genetics.

Galegov, G.A. and A.A. Iatsyna (1980). Ingibiruiushchee deistvie solianokislogo rimantadina (alpha-metil-1-adamantanmetilamina) na sintez belkov virusa grippa. [Inhibitory effect of rimantidine hydrochloride (alpha-methyl-1-adamantan methylamine) on the synthesis of influenza virus proteins]. Doklady Akademii Nauk SSSR 251(2): 481-82.  ISSN: 0002-3264.

            NAL Call Number:  511 P444A

            Descriptors:  adamantane analogs and derivatives, influenza A virus avian drug effects, rimantadine pharmacology, viral proteins biosynthesis, chick embryo, fibroblasts microbiology, avian metabolism, RNA, messenger metabolism.

Galegov, G.A., A.A. Iatsyna, G.L. Linitskaia, and N.L. Pushkarskaia (1976). Ingibiruiushchee deistvie solianokislogo al'fa-metil-1-adamantanmetilamina (rimantadina) na induktsiiu RNK-zavisimoi RNK-polimerazy v kul'ture kletok, infitsirovannykh virusom grilla [Inhibitory effect of alpha-methyl-1-adamantane methylamine hydrochloride (rimantadine) on RNA-dependent RNA polymerase induction in culture of cells, infected with influenza virus]. Biokhimiia Moscow, Russia 41(12): 2237-9.  ISSN: 0320-9725.

            NAL Call Number:  385 B523

            Abstract:  An anti-influenza preparation, rimantadine (alpha-methyl-1-adamantane methylamine hydrochloride) at concentrations of 10--25 mkg/ml depresses the RNA-dependent RNA polymerase induction in a culture of cells infected with influenza virus (fowl plague virus). The inhibitory effect is also observed 2 hours following cell infection. In vitro studies have demonstrated that rimantadine has no effect on the activity of virus-induced RNA-dependent RNA polymerase, as well as on that of RNA-dependent RNA polymerase associated with virus particles.

            Descriptors:  adamantane analogs and derivatives, antiviral agents pharmacology, bridged compounds analogs and derivatives, influenza A virus avian, RNA nucleotidyltransferases biosynthesis, RNA replicase biosynthesis, adamantane pharmacology, cultured cells, enzyme induction drug effects, virus cultivation.

Galegov, G.A., N.A. Pushkarskaia, K.M. Ermolaev, and I.A. Red'kin (1970). Ingibiruiushchee deistvie 2-N-atsetilaminotsikogeksen-2-ona i ego proizvodnykh na reproduktsiiu virusa grippa A v kul'ture tkani. [The inhibiting effect of 2-N-acetylaminocyclohexene-2-one and its derivatives on influenza A virus reproduction in tissue culture]. Voprosy Virusologii 15(6):  689-93.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  antiviral agents pharmacology, cyclohexanes pharmacology, influenza microbiology, influenza A virus avian drug effects, virus replication drug effects, antiviral agents adverse effects, cell line, chick embryo, fibroblasts enzymology, hemagglutinins viral biosynthesis, avian isolation and purification, neuraminidase metabolism, tissue culture.

Gambaryan, A., R. Webster, and M. Matrosovich (2002). Differences between influenza virus receptors on target cells of duck and chicken. Archives of Virology 147(6): 1197-208.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  H5, H7, and H9 subtype influenza viruses in land-based poultry often differ from viruses of wild aquatic birds by deletions in the stalk of the neuraminidase, by the presence of additional carbohydrates on the hemagglutinin, and by occasional changes in the receptor specificity. To test whether these differences could reflect distinctions between the virus receptors in different avian species, we compared the binding of duck, chicken and human influenza viruses to cell membranes and gangliosides from epithelial tissues of duck, chicken and African green monkey. Human viruses bound to cell membranes of monkey and chicken but not to those of duck, suggesting that chicken cells unlike duck cells contain Sia(alpha2-6)Gal-terminated receptors recognized by human viruses. Duck virus bound to gangliosides with short sugar chains that were abundant in duck intestine. Human and chicken viruses did not bind to these gangliosides and bound more strongly than duck virus to gangliosides with long sugar chains that were found in chicken intestinal and monkey lung tissues. Our data suggest that the spectrum of sialylglycoconjugates which can serve as influenza virus receptors in chicken is more similar to the spectrum of receptors in the respiratory epithelia of monkey than to that in the epithelial tissues of duck. This notion could explain the recent emergence of avian H9N2 virus lineage with human virus-like receptor specificity and emphasizes the role of the chicken as a potential intermediate host for the transmission of viruses from aquatic birds to humans.

            Descriptors:  chickens, ducks, influenza A virus avian metabolism, influenza A virus human metabolism, receptors, virus chemistry, receptors, virus metabolism, binding sites, cell membrane metabolism, cercopithecus aethiops, epithelial cells metabolism,  gangliosides chemistry, gangliosides metabolism, oligosaccharides chemistry, oligosaccharides metabolism, receptors, cell surface chemistry, receptors, cell surface metabolism.

Gambaryan, A.S., A.B. Tuzikov, N.V. Bovin, S.S. Yamnikova, D.K. Lvov, R.G. Webster, and M.N. Matrosovich (2003). Differences between influenza virus receptors on target cells of duck and chicken and receptor specificity of the 1997 H5N1 chicken and human influenza viruses from Hong Kong.  Avian Diseases 47(Special Issue): 1154-1160.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  To study whether influenza virus receptors in chickens differ from those in other species, we compared the binding of lectins and influenza viruses with known receptor specificity to cell membranes and gangliosides from epithelial tissues of ducks, chickens, and African green monkeys. We found that chicken cells contained Neu5Acalpha(2-6)Gal-terminated receptors recognized by Sambucus nigra lectin and by human viruses. This finding explains how some recent H9N2 viruses replicate in chickens despite their human virus-like receptor specificity. Duck virus bound to gangliosides with short sugar chains that were abundant in duck intestine. Human and chicken viruses did not bind to these gangliosides and bound more strongly than duck virus to gangliosides with long sugar chains that were found in chicken intestinal and monkey lung tissues. Chicken and duck viruses also differed by their ability to recognize the structure of the third sugar moiety in Sia2-3Gal-terminated receptors. Chicken viruses preferentially bound to Neu5Acalpha(2-3)Galbeta(1-4)GlcNAc-containing synthetic sialylglycopolymer, whereas duck viruses displayed a higher affinity for Neu5Acalpha(2-3)Galbeta(1-3)GalNAc-containing polymer. Our data indicate that sialyloligosaccharide receptors in different avian species are not identical and provide a potential explanation for the differences between the hemagglutinin and neuraminidase proteins of duck and chicken viruses.

            Descriptors:  cell biology, infection, avian influenza, infectious disease, respiratory system disease, viral disease, receptor specificity target cells.

Gambaryan, A.S., A.B. Tuzikov, V.E. Piskarev, S.S. Yamnikova, D.K. Lvov, J.S. Robertson, N.V. Bovin, and M.N. Matrosovich (1997). Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenza B viruses share a common high binding affinity for 6'-sialyl(N-acetyllactosamine). Virology 232(2): 345-50.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Synthetic sialylglycoconjugates bearing 3'-sialyllactose, 6'-sialyllactose, or 6'-sialyl(N-acetyllactosamine) moieties attached to the polyacrylic acid carrier (P-3-SL, P-6-SL, and P-6-SLN, respectively) were prepared and tested for their ability to bind to influenza virus isolates from different hosts in a competitive solid phase assay. The virus panel included egg-grown avian and porcine strains, as well as human viruses isolated and propagated solely in mammalian (MDCK) cells and their egg-adapted variants. A clear correlation was observed between the pattern of virus binding of two glycopolymers, P-3-SL and P-6-SLN, and the host species from which the virus was derived. Avian isolates displayed a high binding affinity for P-3-SL and a two to three orders of magnitude lower affinity for P-6-SLN. By contrast, all non-egg-adapted human A and B viruses bound P-6-SLN strongly but did not bind P-3-SL. Unlike the "authentic" human strains, their egg-adapted counterparts acquired an ability to bind P-3-SL, indicative of a shift in the receptor-binding phenotype toward the recognition of Neu5Ac2-3Gal-terminated sugar sequences. Among the porcine viruses and human isolates with porcine hemagglutinin, few displayed an avian-like binding phenotype, while others differed from both avian and human strains by a reduced ability to discriminate between P-3-SL and P-6-SLN. Our data show that sialylglycopolymers may become a useful tool in studies on molecular mechanisms of interspecies transfer, tissue specificity, and other structure-function relationships of the influenza virus hemagglutinin.

            Descriptors:  amino sugars metabolism, influenza A virus avian metabolism, human metabolism, porcine metabolism, influenza B virus metabolism, lactose analogs and derivatives, receptors, virus metabolism, sialic acids metabolism, amino sugars chemistry, cell line, chick embryo, dogs, glycoconjugates metabolism, human isolation and purification, influenza B virus isolation and purification, lactose chemistry, lactose metabolism, phenotype, receptors, virus chemistry, sialic acids chemistry.

Gambaryan, A., S. Yamnikova, D. Lvov, A. Tuzikov, A. Chinarev, G. Pazynina, R. Webster, M. Matrosovich, and N. Bovin (2005). Receptor specificity of influenza viruses from birds and mammals: new data on involvement of the inner fragments of the carbohydrate chain. Virology 334(2): 276-283.

            NAL Call Number:  448.8 V81

            Abstract:  We studied receptor-binding properties of influenza virus isolates from birds and mammals using polymeric conjugates of sialooligosaccharides terminated with common Neu5Ac[alpha]2-3Gal[beta] fragment but differing by the structure of the inner part of carbohydrate chain. Viruses isolated from distinct avian species differed by their recognition of the inner part of oligosaccharide receptor. Duck viruses displayed high affinity for receptors having [beta]1-3 rather than [beta]1-4 linkage between Neu5Ac[alpha]2-3Gal-disaccharide and penultimate N-acetylhexosamine residue. Fucose and sulfate substituents at this residue had negative and low effect, respectively, on saccharide binding to duck viruses. By contrast, gull viruses preferentially bound to receptors bearing fucose at N-acetylglucosamine residue, whereas chicken and mammalian viruses demonstrated increased affinity for oligosaccharides that harbored sulfo group at position 6 of ([beta]1-4)-linked GlcNAc. These data suggest that although all avian influenza viruses preferentially bind to Neu5Ac[alpha]2-3Gal-terminated receptors, the fine receptor specificity of the viruses varies depending on the avian species. Further studies are required to determine whether observed host-dependent differences in the receptor specificity of avian viruses can affect their ability to infect humans.

            Descriptors:  animals, birds, carbohydrate sequence, chickens, ducks, humans, avian influenza A virus metabolism, avian influenza A virus pathogenicity, human influenza A virus metabolism, human influenza A virus pathogenicity, porcine influenza A virus metabolism, porcine influenza A virus pathogenicity, molecular models, molecular sequence data, oligosaccharides chemistry, oligosaccharides metabolism, virus receptors chemistry, virus receptors metabolism, species specificity, swine, U.S. Government P.H.S. research support, N.I.H. extramural research support, non-U.S. Government research support.

Gamblin, S.J., L.F. Haire, R.J. Russell, D.J. Stevens, B. Xiao, Y. Ha, N. Vasisht, D.A. Steinhauer, R.S. Daniels, A. Elliot, D.C. Wiley, and J.J. Skehel (2004). The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 303(5665): 1838-42.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Abstract:  The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus metabolism, influenza virology, influenza A virus, human immunology, receptors, virus metabolism, amino acid sequence, binding sites, birds, crystallography, x-ray, history, 20th century, hydrogen bonding, influenza epidemiology, influenza history, avian immunology, avian metabolism, human metabolism, human pathogenicity, porcine immunology, porcine metabolism, membrane glycoproteins chemistry, membrane glycoproteins metabolism, models, molecular, molecular sequence data, protein conformation, protein structure, tertiary, sequence alignment, sialic acids metabolism, species specificity, swine.

Gandhi, S.S., H.B. Bell, and D.C. Burke (1971). Abortive infection of L cells by fowl plague virus: comparison of RNA and protein synthesis in infected chick and L cells. Journal of General Virology 13(3): 424-32.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  cultured cells metabolism, influenza A virus avian pathogenicity, l cells cell line, proteins biosynthesis, RNA biosynthesis, antigens, viral metabolism, carbon isotopes, cell fractionation, cell nucleus metabolism,  chick embryo, complement fixation tests, cytopathogenic effect, viral, cytoplasm metabolism, dactinomycin pharmacology, electrophoresis, disc, hemagglutinins viral metabolism, avian enzymology, avian growth and development, avian immunology avian metabolism, neuraminidase metabolism, RNA viral biosynthesis, time factors, tritium,  uridine metabolism, valine metabolism, viral proteins biosynthesis, virus replication.

Garber, E.A., H.T. Chute, J.H. Condra, L. Gotlib, R.J. Colonno, and R.G. Smith (1991). Avian cells expressing the murine Mx1 protein are resistant to influenza virus infection. Virology 180(2): 754-62.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The cDNA encoding the murine Mx1 protein, a mediator of resistance to influenza virus, was inserted into a replication-competent avian retroviral vector in either the sense (referred to as Mx+) or the antisense (referred to as Mx-) orientation relative to the viral structural genes. Both vectors produced virus retaining the Mx insert (Mx recombinant viruses referred to as Mx+ and Mx-) following transfection into chicken embryo fibroblasts (CEF). Mx protein of the appropriate size and nuclear localization was expressed only in CEF cells infected with the Mx+ virus. Mx expression was observed in all Mx(+)-infected cells and was stable during long-term culture. Cells infected with the Mx+ virus were resistant to infection by human influenza A/WSN/33 (H1N1) and avian influenza viruses A/Turkey/Wisconsin/68 (H5N9) and A/Turkey/Massachusetts/65 (H6N2), but were susceptible to infection by the enveloped RNA viruses Sindbis and vesicular stomatitis virus (VSV). Normal CEF and cells infected with the Mx virus were susceptible to influenza A, Sindbis, and VSV. The synthesis of influenza proteins, especially the larger polymerase and hemagglutinin proteins, was reduced in Mx+ retrovirus-infected cells superinfected by influenza A.

            Descriptors:  GTP binding proteins, influenza A virus avian growth and development, growth and development, proteins physiology, transfection, virus inhibitors physiology, cell line, cultured cells, chick embryo, fibroblasts cytology, fluorescent antibody technique, genetic predisposition to disease, immunoblotting, mice, mice, inbred strains, plaque assay, proteins genetics.

Garcia Gancedo, A., E. Ronda, M.L. Alonso, and P. Vilas (1967). Study of a hemagglutination inhibitor from HeLa cells. Microbiologia Espanola 20(3): 203-17.  ISSN: 0026-2595.

            NAL Call Number:  448.3 M583

            Descriptors:  HeLa cells immunology, hemagglutination inhibition tests, influenza A virus avian immunology, methods.

Garcia, M., J.M. Crawford, J.W. Latimer, E. Rivera Cruz, and M.L. Perdue (1996). Heterogeneity in the haemagglutinin gene and emergence of the highly pathogenic phenotype among recent H5N2 avian influenza viruses from Mexico. Journal of General Virology 77(Pt.7): 1493-1504.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Molecular changes in the haemagglutinin (HA)-coding regions and proteolytic cleavage sites from multiple H5N2 subtype viruses isolated during a recent outbreak of avian influenza (AI) in central Mexico have been characterized. Eighteen isolates, collected during a 15 month period (October 1993 to January 1995) from six central states, were sequenced. None of the 18 predicted HA1 amino acid sequences were identical and changes were not restricted to a specific region of the sequence. Phylogenetic analyses of the HA1 sequences demonstrated two virus lineages, designated Puebla and Jalisco, with sequence variation as high as 10.5% for amino acid and 6.2% for nucleotide sequences. During the latter months of the surveillance period, highly pathogenic (HP) strains of AI emerged causing lethal disease in commercial poultry flocks. In each of the HP strains isolated, the HA protein was cleaved in chicken embryo fibroblast cells in the absence of trypsin, and two alterations not found in earlier non-HP isolates were detected. In the HA protein, HP strains all had a glutamic acid replaced by lysine substitution at amino acid position 324 and an insertion of arginine and lysine as new residues 325 and 326. The insertion appears to be due to a duplication of the nucleotide sequence AAAGAA at nucleotide positions 965-970 of the HA1-coding region. Computer-assisted secondary structure analyses place the target for the insertion in a predicted RNA stem-loop structure. A mechanism is suggested by which the polymerase duplicates the sequence.

            Descriptors:  avian influenza virus, structural genes, viral hemagglutinins, nucleotide sequences, amino acid sequences, pathogenicity, phenotypes, heterogeneity, phylogeny, molecular conformation, Mexico, secondary structure, cleavage site sequence, molecular sequence data, GENBANK u37165, GENBANK u37166, GENBANK u37167, GENBANK u37168, GENBANK u37168, GENBANK u37169, GENBANK u37170, GENBANK u37171, GENBANK u37172, GENBANK u37173, GENBANK u37174, GENBANK u37175, GENBANK u37176, GENBANK u37177, GENBANK u37178, GENBANK u37179, GENBANK u37180, GENBANK u37181, GENBANK u37182.

Garcia Sastre, A., A. Egorov, D. Matassov, S. Brandt, D.E. Levy, J.E. Durbin, P. Palese, and T. Muster (1998). Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252(2): 324-30.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  gene deletion, influenza physiopathology, influenza A virus avian genetics, viral nonstructural proteins genetics, virus replication, cell line, Cercopithecus aethiops, chick embryo, DNA binding proteins genetics, DNA binding proteins physiology, dogs, influenza genetics, influenza A virus avian physiology, kidney, mice, mice inbred BALB c, mice, inbred c57bl, mice, knockout, signal transduction, trans activators genetics, trans activators physiology,  transfection, vero cells, viral nonstructural proteins metabolism.

Gardner, I.D. and K.F. Shortridge (1979). Recombination as a mechanism in the evolution of influenza viruses: a two-year study of ducks in Hong Kong. Reviews of Infectious Diseases 1(5): 885-90.  ISSN: 0162-0886.

            NAL Call Number:  RC111.R4

            Abstract:  An analysis was made of 149 influenza A viruses isolated from ducks in Hong Kong during the period of November 1975 through October 1977. The viruses were isolated five times more frequently from ducks raised in the People's Republic of China than from those raised in Hong Kong. The isolation rate fo viruses was higher from the cloaca than it was from the trachea, but this pattern varied over the two years of investifation. The large number of different combinations (30) of hemagglutinin and neuraminidase genes suggests that recombination of viruses was taking place. Analysis of these combinations showed that their distribution was not random and that certain combinations occured more frequently, and others less frequently, than was expected. The recombination of influenza viruses and the excess or restriction of certain combinations may have implications for the evolution of pandemic strains of influenza virus in humans.

            Descriptors:  ducks microbiology, influenza A virus avian genetics, recombination, genetic, China, cloaca microbiology, evolution, gene frequency, genotype, hemagglutinins viral genetics, Hong Kong, influenza A virus avian isolation and purification, neuraminidase genetics, paramyxoviridae isolation and purification, seasons, trachea microbiology.

Garten, W., S. Hallenberger, D. Ortmann, W. Schaefer, M. Vey, H. Angliker, E. Shaw, and H.D. Klenk (1994). Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones. Biochimie Paris 76(3-4): 217-225.  ISSN: 0300-9084.

            NAL Call Number:  383 So1

            Abstract:  The spike glycoproteins of many enveloped viruses are proteolytically cleaved at the carboxytermini of sequences containing the basic motif R-X-K/R-R. Cleavage is often necessary for the fusion capacity of the glycoproteins and, thus, for virus infectivity. Among these viruses are pathogenic avian influenza viruses, human parainfluenza virus, human cytomegalovirus, and human immunodeficiency virus; it has been demonstrated that these viruses can be activated by furin. Indigenous furin has been identified in T-lymphocytes, which are host cells for HIV. Furin has been localized in the TGN and on the surface of cells after vectorial expression. Peptidylchloroalkylketones have been designed that inhibit with high specificity cleavage and fusion activity of viral glycoproteins, as well as virus replication.

            Descriptors:  blood and lymphatics, cell biology, enzymology, genetics, infection, membranes, metabolism, microbiology, molecular genetics, avian influenza viruses, cell surface, cleavage, fusion activity, glycoprotein fusion, human parainfluenza virus, T lymphocyte, trans Golgi network, viral infectivity, virus infectivity, virus replication.

Garten, W., D. Linder, R. Rott, and H.D. Klenk (1982). The cleavage site of the hemagglutinin of fowl plague virus. Virology 122(1): 186-90.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian metabolism, protein precursors metabolism, amino acid sequence, peptide fragments analysis, protein processing, post translational.

Garten, W., A. Stieneke, E. Shaw, P. Wikstrom, and H.D. Klenk (1989). Inhibition of proteolytic activation of influenza virus hemagglutinin by specific peptidyl chloroalkyl ketones. Virology 172(1): 25-31.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Lysates of cultured cells have been analyzed for arginine-specific endoproteases using peptidyl-p-nitroanilides as chromogenic substrates. The enzymes present in MDBK, MDCK, VERO, BHK, and chick embryo cells required lysine-arginine or arginine-arginine pairs as cleavage sites, whereas chorioallantoic membrane cells contained, in addition, an activity that could cleave at a single arginine. The effect of peptidyl chloroalkyl ketones on the activation of the fowl plague virus hemagglutinin by the proteases specific for paired basic residues has been investigated. When virions containing uncleaved hemagglutinin were incubated with lysates of uninfected cells, cleavage was completely inhibited by peptidyl chloroalkyl ketones containing paired basic residues at a concentration of 1 mM. In contrast a compound containing a single arginine had no inhibitory activity. When dibasic peptidyl chloroalkyl ketones were added to infected cell cultures, cleavage of hemagglutinin and multiple cycles of virus replication were inhibited at 10 mM. However, a 100- to 200-fold increase of the inhibitory activity in intact cells could be achieved by N-terminal acylation. These studies suggest a potential role of peptidyl chloroalkyl ketones as antiviral agents.

            Descriptors:  amino acid chloromethyl ketones pharmacology, hemagglutinins viral metabolism, influenza A virus avian metabolism, protease inhibitors pharmacology, protein processing, post translational drug effects, cell membrane enzymology, cultured cells, dogs, molecular weight, protease inhibitors chemical synthesis, structure activity relationship, virus replication.

Garten, W., M. Vey, R. Ohuchi, M. Ohuchi, and H.D. Klenk (1991). Modification of the cleavage activation of the influenza virus hemagglutinin by site-specific mutagenesis. Behring Institute Mitteilungen (89): 12-22.  ISSN: 0301-0457.

            NAL Call Number:  QR180.B4

            Abstract:  Factors determining cleavability of influenza virus hemagglutinin which is activated by ubiquitous cellular endoproteases were analysed by carrying out site-directed mutagenesis on the cloned hemaglutinin genes of strains A/FPV/Rostock/34 (subtype H7) and A/Port Chalmers/1/73 (subtype H3). Substitutions at the cleavage site of the H7 hemagglutinin indicate that the tetrapeptide Arg-X-Lys/Arg-Arg is the minimal consensus sequence recognized by the ubiquitous proteases. The H3 hemagglutinin also became susceptible to these enzymes, when additional arginines were inserted at the cleavage site. Three arginines were sufficient, when the carbohydrate was removed, whereas four additional arginines are needed when this carbohydrate was present, indicating that the accessibility of the cleavage motif is important for the protease. The appropriate localization of the basic cleavage motif within the amino acid sequence and the spatial structure of the hemagglutinin precursor is an additional prerequisite for cleavage.

            Descriptors:  endopeptidases metabolism, genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, mutagenesis, site directed, amino acid sequence, base sequence, cell fusion, cell line, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral metabolism, influenza A virus avian immunology, molecular sequence data, oligodeoxyribonucleotides, recombinant proteins metabolism, viral envelope proteins genetics.

Garten, W., C. Will, K. Buckard, K. Kuroda, D. Ortmann, K. Munk,  C. Scholtissek, H. Schnittler, D. Drenckhahn, and H.D. Klenk (1992). Structure and assembly of hemagglutinin mutants of fowl plague virus with impaired surface transport. Journal of Virology 66(3): 1495-505.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Five temperature-sensitive mutants of influenza virus A/FPV/Rostock/34 (H7N1), ts206, ts293, ts478, ts482, and ts651, displaying correct hemagglutinin (HA) insertion into the apical plasma membrane of MDCK cells at the permissive temperature but defective transport to the cell surface at the restrictive temperature, have been investigated. Nucleotide sequence analysis of the HA gene of the mutants and their revertants demonstrated that with each mutant a single amino acid change is responsible for the transport block. The amino acid substitutions were compared with those of mutants ts1 and ts227, which have been analyzed previously (W. Schuy, C. Will, K. Kuroda, C. Scholtissek, W. Garten, and H.-D. Klenk, EMBO J. 5:2831-2836, 1986). With the exception of ts206, the changed amino acids of all mutants and revertants accumulate in three distinct areas of the three-dimensional HA model: (i) at the tip of the 80-A (8-nm)-long alpha helix, (ii) at the connection between the globular region and stem, and (iii) in the basal domain of the stem. The concept that these areas are critical for HA assembly and hence for transport is supported by the finding that the mutants that are unable to leave the endoplasmic reticulum at the nonpermissive temperature do not correctly trimerize. Upon analysis by density gradient centrifugation, cross-linking, and digestion with trypsin and endoglucosaminidase H, two groups can be discriminated among these mutants: with ts1, ts227, and ts478, the HA forms large irreversible aggregates, whereas with ts206 and ts293, it is retained in the monomeric form in the endoplasmic reticulum. With a third group, comprising mutants ts482 and ts651 that enter the Golgi apparatus, trimerization was not impaired.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian metabolism, membrane glycoproteins metabolism, amino acid sequence, base sequence, biological transport, cell membrane metabolism, cell polarity, hemagglutinins viral chemistry, hemagglutinins viral genetics, influenza A virus avian genetics, macromolecular systems, membrane glycoproteins chemistry, membrane glycoproteins genetics, molecular sequence data, protein binding, protein conformation, protein processing, post translational, RNA viral genetics.

Geisler, B., W. Seidel, and L. Dohner (1987). Untersuchung zum Vergleich des Nukleoproteins aviarer und humaner Influenzavirusstamme. [Comparison of nucleoproteins of avian and human influenza virus types]. Archiv Fur Experimentelle Veterinarmedizin 41(5): 686-91.  ISSN: 0003-9055.

            NAL Call Number:  41.8 Ex7

            Descriptors:  influenza A virus avian genetics, influenza A virus human genetics, nucleoproteins analysis, birds, electrophoresis, polyacrylamide gel, peptide mapping.

Geisler, B., W. Seidel, B. Herrmann, and L. Dohner (1986). Differences of nucleoproteins of human and avian influenza A virus strains shown by polyacrylamide gel electrophoresis and by the peptide mapping technique. Archives of Virology 90(3-4): 289-99.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Electrophoretic mobility differences in polyacrylamide gels were detected between (35S)-methionine-labelled nucleoproteins (NPs) induced in monolayer cells by 15 human and 4 avian reference strains of influenza viruses. The (35S)-methionine-labelled tryptic peptides of nucleoproteins of these strains were also analyzed by peptide mapping technique. Based on several detectable hydrophilic peptides the NPs could be arranged in 7 clearly differentiable groups. After radioiodination of NPs from 4 human and 3 avian reference strains the tryptic peptide patterns showed one clear difference between human and avian strains.

            Descriptors:  influenza A virus analysis, nucleoproteins analysis, viral proteins analysis, electrophoresis, polyacrylamide gel, influenza A virus avian analysis, influenza A virus avian genetics, influenza A virus human analysis, influenza A virus human genetics, influenza A virus genetics, peptide fragments analysis, variation genetics.

Geisler, B., V. Zeidel, B. Herrmann, and L. Dener (1986). Variatsii belka NP virusa grippa, vyiavliaemye posredstvom peptidnogo kartirovaniia i elektroforeza v poliakrilamidnom gele. [Variations in the NP protein of the influenza virus detected by peptide mapping and polyacrylamide gel electrophoresis]. Voprosy Virusologii 31(5): 538-44.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  NP proteins of 19 reference and 42 epidemic strains of influenza A virus were analysed for their mobility in polyacrylamide gel electrophoresis and distribution of tryptic peptides. The strains could be divided into 4 groups by differences in their electrophoretic mobility, and into 9 groups according to reproducible differences of several hydrophilic peptides determined by peptide mapping.

            Descriptors:  influenza A virus avian analysis, influenza A virus human analysis, nucleoproteins analysis, variation genetics, viral proteins analysis, birds, electrophoresis, polyacrylamide gel methods, East Germany, peptide mapping methods, viral structural proteins.

Gendon, I.U.Z. (1977). Vliianie obrabotki neiraminidazoi fibroblastov kurinogo embriona na adsorpbtsiiu i reproduktsiiu virusa chumy ptits. [Effect of neuraminidase treatment of chick embryo fibroblasts on the adsorption and reproduction of the fowl plague virus]. Voprosy Virusologii (4): 429-32.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Treatment with neuraminidase (100 units/ml) of chick embryo fibroblasts in vitro only partially inhibits adsorption of fowl plague virus on these cells. Cultivation of chick embryo fibroblasts in the presence of 50 units/ml neuraminidase had no effect on the sensitivity of these cells to fowl plague virus and on the extent of virus reproductions. It is suggested that neuraminic acid which is a component of the external cell membrane is not only substance responsible for adsorption of orthomyxoviruses.

            Descriptors:  influenza A virus avian drug effects, neuraminidase pharmacology, virus replication drug effects, adsorption, chick embryo, dose response relationship, drug, fibroblasts drug effects, time factors, virus cultivation.

Gendon, I.U.Z., V.P. Ginzburg, G.I.A. Solov'ev, and L.M. Babushkina (1969). Izmenenie sinteza RNK v kletkakh kul'tury tkani, infitsirovannoi miksovirusami. [Changes in RNA synthesis in tissue culture cells infected with myxoviruses]. Voprosy Virusologii 14(5): 526-32.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  influenza A virus avian metabolism, Newcastle disease virus metabolism, RNA biosynthesis, radiation effects, carbon isotopes, chick embryo, cycloheximide pharmacology, fibroblasts metabolism, fowl plague metabolism, influenza A virus avian radiation effects,  Newcastle disease metabolism, Newcastle disease virus radiation effects, RNA nucleotidyltransferases metabolism, tissue culture, ultraviolet rays, uridine metabolism.

Gendon, I.U.Z., S.G. Markushin, and S.I.A. Mel'nikova (1986). Vliianie remantadina na gemoliticheskuiu aktivnost' gemaggliutinina virusa grippa. [Effect of remantadine on the hemolytic activity of influenza virus hemagglutinin]. Voprosy Virusologii 31(4): 414-20.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  adamantane analogs and derivatives, hemagglutinins viral immunology, hemolysis drug effects, influenza A virus avian drug effects, influenza A virus human drug effects, rimantadine pharmacology, drug resistance, microbial, genes viral drug effects, hydrogen-ion concentration, influenza A virus avian genetics, influenza A virus avian immunology, influenza A virus human genetics, influenza A virus human immunology, protease inhibitors pharmacology, recombination, genetic drug effects.

Generalov, V.M., T.S. Bakirov, A.G. Durymanov, A.N. Sergeev, L.N. Shishkina, V.A. Petrishchenko, V.S. Toporkov,  G.I. Tyunnikov, A.A. Medvedev, V.D. Poryvaev, and O.V. Fefelov (2002). Study of virus-cell interaction by the method of dielectrophoresis. Doklady. Biochemistry and Biophysics 383: 82-4.  ISSN: 1607-6729.

            NAL Call Number:  QP501.D65

            Descriptors:  cell physiology, cells virology, viral physiology, viruses radiation effects, cells radiation effects, chickens, electromagnetic fields, erythrocytes physiology,  erythrocytes virology, haplorhini, influenza A virus avian physiology.

Gerber, A., C. Sauter, and J. Lindenmann (1973). Fowl plague virus adapted to human epithelial tumor cells and human myeloblasts in vitro. I. Characteristics and replication in monolayer cultures. Archiv Fur Die Gesamte Virusforschung 40(1): 137-51.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian growth and development, virus cultivation, virus replication, bone marrow microbiology, bone marrow cells, carcinoma, bronchogenic, cell line, chick embryo, clone cells, cytological techniques, cytopathogenic effect, viral, diploidy, epithelial cells, epithelium microbiology, fibroblasts microbiology, HeLa cells, hemagglutination inhibition tests, leukemia, myelocytic, acute, plaque assay.

Gerber, A., C. Sauter, and J. Lindenmann (1973). Fowl plague virus adapted to human epithelial tumor cells and human myeloblasts in vitro. II. Replication in human leukemic myoloblast cultures. Archiv Fur Die Gesamte Virusforschung 40(3): 255-64.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  bone marrow microbiology, bone marrow cells, influenza A virus avian growth and development, leukemia, myelocytic, acute microbiology, virus replication, adult, aged, cultured cells, hemadsorption, influenza A virus avian pathogenicity, middle aged, virulence, virus cultivation.

Gerganov, G. and K. Surtmadzhiev (1982). Kultivirane na niakoi ptichi virusi v trakhealni organni kulturi ot fazani i kokoshi zarodishi. [Cultivation of various avian viruses in pheasant trachea organ cultures and chick embryos]. Veterinarnomeditsinski Nauki 19(2): 18-24.  ISSN: 0324-1068.

            NAL Call Number:  41.8 V6468

            Abstract:  Stationary tracheal organ cultures of pheasants and chick embryos, treated with a mucolytic agent were used to study the ciliostatic effect of the following viruses: fowl pest (FPV), Newcastle disease (NDV), infections laryngotracheitis (ILV), and infections bronchitis (IBV) - strain Beaudette. In chick embryo tracheal cultures ciliostasis was found to set in as follows: for FPV - at the 24th hour; for NDV - at the 72nd-120th hour; for ILV - at the 168-192nd hour; and for IBV-at the 72nd-96th hour. The ciliostatic effect produced  by NDV and IBV coincided in terms of time and dynamics. In pheasant tracheal organ cultures ciliostasis set in as follows: for FPV - at the 24th hour; for NDV - at the 72nd-120th hour; and for ILV - at the 168-192nd hour. This system was shown to be unsusceptible to IBV which produced no effect whatever. In mixed organic cultures, containing several tracheal segments of pheasants and chick embryos each per petri dish IBV did bring about ciliostasis in the chick embryo segments only, within the period after inoculation as cited above. It is stated that pheasant tracheal organ cultures could be employed in the case of an express initial differentiation of FPV, NDV, and ILV, recording the time period for the setting in of full ciliostasis following the inoculation of the respective viruses. Discussed is the possibility of identifying IBV, using mixed tracheal organ cultures of pheasants and chick embryos.

            Descriptors:  coronaviridae growth and development, herpesviridae growth and development, herpesvirus 1, gallid growth and development, infectious bronchitis virus growth and development, influenza A virus avian growth and development, Newcastle disease virus growth and development, birds, chick embryo, organ culture, trachea, virus cultivation methods.

Germanov, A.B. (1976). A genetic approach to studies on the synthesis of the complementary RNA's of fowl plague virus. Journal of General Virology 31(3): 281-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The rate of incorporation of 5-fluorouracil into complementary strands of replicating RNA of fowl plague virus (FPV) has been studied. The efficiency of incorporation was estimated by determination of the reversion frequency in s-mutants with known types of base transitions in the RNA of the virus particle. It was established that maximum incorporation of 5-fluorouracil into progeny virus particle RNA took place between 2 and 4 h after infection. The maximum incorporation of the mutagen into complementary RNA (plus strands) occurred when the cells were exposed to 5-fluorouracil from 1 to 2 h after infection.

            Descriptors:  influenza A virus avian metabolism, mutation, RNA viral biosynthesis, base sequence,  ethyl methanesulfonate pharmacology, fluorouracil metabolism, fluorouracil pharmacology, hydroxylamines pharmacology, influenza A virus avian growth and development, mutagens, nitrous acid pharmacology, virus replication.

Germanov, A.B., N.A. Parasiuk, and M.I. Sokolov (1973). Study on the mutagenic action of O-methylhydroxylamine on RNA viruses (on the model of fowl plague virus). Acta Virologica 17(5): 377-83.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  hydroxylamines pharmacology, influenza A virus avian drug effects, mutagens pharmacology, mutation drug effects, cultured cells, chick embryo, cytosine metabolism, hydrogen-ion concentration, influenza A virus avian metabolism, influenza A virus avian pathogenicity, plaque assay, RNA viral metabolism, time factors, uracil metabolism.

Germanov, A.B., M.I. Sokolov, I.A. Myasnikova, N.A. Parasiuk, T.V. Vorontsova, and G.V. Kornilaeva (1972). Some biological and physico-chemical properties of plaque mutants of fowl plague virus. Brief report. Archiv Fur Die Gesamte Virusforschung 39(4): 389-92.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian drug effects, influenza A virus avian radiation effects, mutation, centrifugation, density gradient, chick embryo, chromatography, DEAE-cellulose, fibroblasts, mutagens, protamines pharmacology, radiation effects, sodium chloride, temperature, tissue culture, ultraviolet rays, virus replication.

Germanov, A.B., M.I. Sokolov, and N.A. Parasiuk (1972). The application of DEAE-cellulose column chromatography to the selection of S+ revertants and determination of reversion frequency in populations of S- mutants of fowl plague virus. Journal of General Virology 17(1): 49-54.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  chromatography, DEAE-cellulose, influenza A virus avian isolation and purification, mutation, chick embryo, culture media, evaluation studies, fibroblasts, genetics, microbial,  hemagglutination tests, hydroxylamines, influenza A virus avian growth and development, mutagens, protamines, sodium chloride, tissue culture.

Germanov, A.B., M.I. Sokolov, and T.V. Vorontsova (1971). Nekotorye aspekty vzaimodeistviia khimicheskikh mutagenov s reprodutsiruiushcheisia populiatsiei RNKsoderzhanschikh virusov. [Some aspects of the interaction of chemical mutagens with reproducing populations of RNA-containing viruses]. Vestnik Akademii Meditsinskikh Nauk SSSR 26(2): 69-74.  ISSN: 0002-3027.

            Descriptors:  genetics, microbial, influenza A virus avian drug effects, mutagens, virus replication drug effects, acridines, azirines, mutation, nitroso compounds.

Gharagozlou, M.J. and B. Samadieh (1980). Cytopathogenicity of two avian influenza A viruses in different cell cultures. Clinica Veterinaria  103(3): 132-137.  ISSN: 0009-9082.

            NAL Call Number:  41.8 C61

            Descriptors:  cell culture, cytopathogenicity, avian influenza virus, turkeys.

Gharagozou, M.J. and B. Samadieh (1994). Cytopathogenicity of two avian influenza viruses in different cell cultures. Archive of the Faculty of Veterinary Medicine, Tehran University 6: 174-184.

            Descriptors:  cell culture, cytopathogenicity, avian influenza virus, poultry.

Ghendon, Y. and O. Blagoveshienskaya (1975). Polyadenylate sequences of fowl plague virus complementary RNA (cRNA) synthesized in vivo and in vitro. Virology 68(2): 330-7.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian analysis, poly A analysis, RNA viral analysis, adenine nucleotides analysis, base sequence, cell free system, influenza A virus avian metabolism, RNA viral biosynthesis, viral isolation and purification, tissue culture, viral proteins analysis, viral proteins biosynthesis.

Ghendon, Y., V.P. Ginsburg, G.Y. Soloviev, and S.G. Markushin (1970). The fate of influenza virus RNA in cells treated with ultraviolet rays. Journal of General Virology 6(2): 249-55.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  fibroblasts radiation effects, influenza A virus avian metabolism, RNA viral biosynthesis, ultraviolet rays, carbon isotopes, chick embryo, fibroblasts enzymology, RNA viral analysis, radiation effects, ribonucleases metabolism, thymidine biosynthesis, tissue culture, uridine biosynthesis, virus replication.

Ghendon, Y., A. Klimov, O. Blagoveshenskaya, and D. Genkina (1979). Investigation of recombinants of human influenza and fowl plague viruses. Journal of General Virology 43(1): 183-91.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Recombinants of human influenza type A viruses, A/Krasnodar/101/1959 (H2N2) or A/Habarovsk/15/1976 (H3N2), and fowl plague virus (FPV), strain Weybridge (Hav1Neq1) were obtained. The genome of the recombinant obtained by recombination of influenza A/Habarovsk/15/1976 virus and FPV contained the genes 4 (HA) and 6 (NA) derived from the influenza A/Habarovsk virus and all the other genes [1, 2, 3, 5 (NP), 7 (M), 8 (NS)] from FPV. The genome of the recombinant of A/Krasnodar/101/1959 virus and FPV contained the genes 2, 4 (HA) and 6 (NA) derived from influenza A/Krasnodar virus and all the other genes [1, 3, 5, (NP), 7 (M), 8 (NS)] from FPV. The recombinants, like FPV, gave high virus yields in chick embryos and could multiply at high temperatures (40 and 42 degrees C), but, like human influenza viruses, were non-pathogenic for chickens and did not replicate in chick embryo fibroblast culture, but did replicate in a human conjunctiva cell line, clone 1-5C-4. The virion transcriptase of the recombinants, in a number of properties determined in vitro, was similar to FPV transcriptase but not to the human influenza virus enzyme.

            Descriptors:  influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic, chick embryo, influenza A virus avian analysis, influenza A virus human analysis, peptides analysis, RNA viral analysis, viral proteins analysis, virus replication.

Ghendon, Y., S. Markushin, V. Ginzburg, and A. Hay (1983). Functional defects of fowl plague virus temperature-sensitive mutant having mutation in the neuraminidase. Archives of Virology 75(1-2): 55-70.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A fowl plague virus (FPV) temperature-sensitive mutant ts 5 having mutation lesions in the gene coding for the neuraminidase has been obtained. The mutant induced synthesis of cRNA, vRNA and proteins in cells under non-permissive conditions, but formation of virions including non-infectious ones was defective. The neuraminidase and haemagglutinin synthesized under non-permissive conditions possessed functional activity and could migrate from the rough endoplasmic reticulum into plasma membranes; however, cleavage of the haemagglutinin was reduced. In ts 5-infected cells under non-permissive conditions the synthesis of segments 5 and 8 of cRNA and vRNA was predominant both early and late in the reproduction cycle, and the synthesis of P1, P2, P3, HA and M proteins was reduced after approximately 3 hours. The data obtained suggest that involvement of the neuraminidase in the formation of infectious virions may have no direct association with the enzymatic activity of this protein, and that the mutation in the neuraminidase may affect regulation of replication and transcription processes.

            Descriptors:  defective viruses genetics, influenza A virus avian genetics, neuraminidase genetics, cell membrane metabolism, genes viral, hemagglutinins viral genetics, influenza A virus human genetics, mutation, RNA viral analysis, recombination, genetic, temperature, viral proteins biosynthesis.

Ghendon, Y., S. Markushin, H. Heider, S. Melnikov, and V. Lotte (1986). Haemagglutinin of influenza A virus is a target for the antiviral effect of Norakin. Journal of General Virology 67(Pt. 6): 1115-22.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The anticholinergic anti-parkinsonism drug Norakin is an inhibitor of influenza virus multiplication. By crossing a Norakin-resistant variant of fowl plague virus (FPV) strain Weybridge with the sensitive FPV/Rostock/34 wild-type virus, Norakin-resistant recombinants were obtained. Analyses of the gene composition showed that all Norakin-resistant recombinants had inherited their haemagglutinin gene from the Norakin-resistant parent strain. The majority of the recombinants had received all the other gene segments from the sensitive parent strain. Norakin was shown to inhibit red blood cell lysis induced either by purified virions or by the haemagglutinin of a sensitive FPV strain at low pH, but failed to affect the Norakin-resistant FPV variant. No aggregation of autoliposomes containing the haemagglutinin of a sensitive FPV strain or digestion of the HA1 subunit of haemagglutinin by trypsin occurred in the presence of Norakin at acid pH. The data suggest that the haemagglutinin of FPV is the target for the antiviral activity of Norakin, which acts by inhibiting the conformational change in the haemagglutinin at acid pH important for lysis.

            Descriptors:  hemagglutinins viral genetics, hemagglutinins viral metabolism, influenza A virus avian drug effects, piperidines pharmacology, cultured cells, chick embryo, drug resistance, microbial, genes viral, hemagglutination drug effects, hemolysis drug effects, hydrogen-ion concentration, liposomes, membrane fusion drug effects, recombination, genetic, trypsin metabolism, virus replication drug effects.

Ghendon, Y., S. Markushin, K. Lisovskaya, C.R. Penn, and B.W. Mahy (1982). Extragenic suppression of a ts phenotype during recombination between ts mutants of two fowl plague virus strains with a ts mutation in gene 1. Journal of General Virology 62(Pt. 2): 239-48.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Fowl plague virus (FPV) ts mutants belonging to six recombination groups and obtained from the Weybridge strain (in the U.S.S.R.) or the Rostock strain (in the U.K.) have been studied in a recombination test. Temperature-sensitive mutants obtained from different FPV strains were revealed which had a ts mutation in gene 1; however, their crossing resulted in ts+ recombinants which appeared with a high frequency. This phenomenon was due not to intragenic complementation but to extragenic suppression, when the expression of a ts phenotype of the Rostock strain mutant gene 1 is suppressed by gene 2 products of the Weybridge strain.

            Descriptors:  influenza A virus avian genetics, gene expression regulation, genes viral, mutation, recombination, genetic, suppression, genetic, temperature.

Ghendon, Y.U.Z. and A.I. Klimov (1981). Effects of edeine, hygromycin B and alpha-Sarcin on influenza virus reproduction. Acta Virologica 25(3): 129-37.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The effects of edeine, hygromycin B and alpha-sarcin on the synthesis of virus-specific proteins and formation of infectious virions was studied in cells infected with fowl plague virus (FPV). The manifestation of the antiviral effect of edeine depended on the peculiarities of the FPV strains and the host-cell systems. Hygromycin B inhibited significantly the synthesis of virus-specific proteins and the formation of the infectious virions, but did not influence protein synthesis in uninfected cells. Alpha-Sarcin in the concentrations tested neither showed a marked antiviral activity nor affected protein synthesis in the uninfected cells.

            Descriptors:  anti bacterial agents pharmacology, edeine pharmacology, endoribonucleases, fungal proteins pharmacology, hygromycin B pharmacology, influenza A virus avian drug effects, virus replication drug effects, cell line, chick embryo, hamsters, influenza A virus avian growth and development, influenza A virus avian metabolism, kidney, tissue culture, viral proteins biosynthesis.

Ghendon, Y.U.Z. and T.A. Mikhailovskaya (1982). Effect of kanamycin on the reproduction of orthomyxoviruses. Acta Virologica 26(4): 241-6.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Kanamycin sulphate at a concentration of 8 mmol/l had no effect on the protein synthesis in uninfected chick embryo cell (CEC) cultures, but caused a 2-fold decrease of virus-specific protein synthesis in CEC infected with fowl plague virus (FPV). Kanamycin at a concentration of 2 mmol/l decreased the yield of infectious FPV in one growth cycle experiments on CEC culture by 1.5 log10 units and when added into the agar overlay it decreased the plaque number by nearly 1 log10 unit. Inoculation of 10 mg of kanamycin into a chick embryo decreased the yield of virus by 1.0 log10. Administration of kanamycin to mice (5-10 mg for three days post infection) reduced mortality of the animals 2--3-fold. Antibiotics of the streptomycin group presumably may penetrate into orthomyxovirus-infected cells due to virus-induced impairment of leakiness of the cell membrane and inhibit both the virus protein synthesis and formation of infectious virions.

            Descriptors:  influenza A virus avian drug effects, influenza A virus human drug effects, kanamycin pharmacology, cultured cells, chick embryo, influenza A virus avian growth and development, influenza A virus human growth and development, influenza A virus human pathogenicity, mice, proteins biosynthesis.

Ghendon, Y.Z., V.P. Ginsburg, G.Y. Soloviev, and L. Babushkina (1969). Effect of myxovirus infection on synthesis of cellular ribonucleic acid. Journal of Virology 3(3): 351-2.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  influenza A virus avian, Newcastle disease virus, RNA biosynthesis, carbon isotopes, chick embryo, cytosine nucleotides metabolism, fibroblasts, RNA nucleotidyltransferases metabolism, tissue culture, uridine metabolism, virus replication.

Ghendon, Y.Z., A.T. Marchenko, S.G. Markushin, D.B. Ghenkina, A.V. Mikhejeva, and E.E. Rozina (1973). Correlation between TS phenotype and pathogenicity of some animal viruses. Archiv Fur Die Gesamte Virusforschung 42(2): 154-9.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian pathogenicity, mutation, polioviruses pathogenicity, brain microbiology, chick embryo, chickens, cytopathogenic effect, viral, genetic complementation test, haplorhini, HeLa cells, influenza A virus avian growth and development, influenza A virus avian isolation and purification, Macaca, mutagens, phenotype, polioviruses growth and development, polioviruses isolation and purification, spinal cord microbiology, temperature, tissue culture, virus cultivation, virus replication.

Ghendon, Y.Z. and S.G. Markushin (1980). Studies on mutation lesions and physiology of fowl plague virus ts mutants. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 288(1029): 383-92.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  Temperature-sensitive (ts) mutants of fowl plague virus (FPV) were divided into six complementation groups. Experiments with ts mutants having defects of transcription showed that in FPV strain Weybridge, protein P1 coded by gene N2 takes part in primary transcription, and protein P3 coded for by gene N1 takes part in secondary transcription. Ts mutants of FPV with lower pathogenicity were present in all six complementation groups under study. Simultaneous inoculation of chickens with two pathogenic ts mutants of FPV caused death of the chickens and a pathogenic virus with ts+ phenotype was isolated from their organs. By recombination of ts multimutant FPV with human influenza virus a recombinant was obtained that contained genes coding for the haemagglutinin and neuraminidase of human influenza virus; all other genes were derived from FPV. In experiments on volunteers this recombinant appeared to be non-reactogenic but capable of inducing antibody formation.

            Descriptors:  influenza A virus avian genetics, mutation, chickens, hemagglutinins viral genetics, influenza A virus avian pathogenicity, influenza A virus human genetics, RNA viral biosynthesis, recombination, genetic, transcription, genetic, translation, genetic, vaccination, virus replication.

Ghendon, Y.Z., S.G. Markushin, O.V. Blagovezhenskaya, and D.B. Genkina (1975). Study of fowl plague virus RNA synthesis in temperature-sensitive mutants. Virology 66(2): 454-63.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, RNA viral biosynthesis, chick embryo, DNA directed RNA polymerases metabolism, dactinomycin pharmacology, electrophoresis, polyacrylamide gel, fibroblasts, genetic complementation test, influenza A virus avian enzymology, mutation, phenotype, temperature, tissue culture, transcription, genetic, uridine metabolism, viral proteins biosynthesis.

Ghendon, Y.Z., S.G. Markushin, A.I. Klimov, and A.J. Hay (1982). Studies of fowl plague virus temperature-sensitive mutants with defects in transcription. Journal of General Virology 63(Pt. 1): 103-11.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Two fowl plague virus temperature-sensitive (ts) mutants belonging to different complementation groups were studied. Both were defective in the syntheses of unpolyadenylated complementary RNA [A(-)cRNA] and virus RNA (vRNA) at non-permissive temperature whereas primary transcription was unaffected. In addition, ts 29, in which the ts mutation is in gene 1 coding for polypeptide P3, has a defect in 'secondary' synthesis of mRNA at non-permissive temperature whereas inhibition of mRNA synthesis by ts 131, in which the ts mutation is in gene 2 coding for polypeptide P1, appeared to result from a defect in vRNA synthesis. These results indicate, therefore, that different enzymes are responsible for the syntheses of virus mRNAs and A(-)cRNAs, which is consistent with the apparent differences in initiation and termination of transcription in the two reactions. The patterns of synthesis of the various types of virus RNA during infection are discussed.

            Descriptors:  genes viral, influenza A virus avian genetics, transcription, genetic, cycloheximide pharmacology, influenza A virus avian metabolism, mutation, RNA, messenger biosynthesis, RNA viral biosynthesis, temperature, viral proteins genetics.

Ghendon, Y.Z., S.G. Markushin, A.I. Klimov, V.D. Lotte, and V.P. Ginzburg (1983). Studies on a temperature-sensitive mutant of fowl plague virus having a mutation in gene 7 coding for the M protein. Journal of General Virology 64(Pt. 2): 291-304.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  A fowl plague virus (FPV) temperature-sensitive mutant, ts 303/1 having a ts mutation in gene 7 coding for the matrix (M) protein has been obtained. The mutant induced synthesis of virus-specific RNA and polypeptides as well as ribonuclear protein (RNP) formation in cells under non-permissive conditions; however, haemagglutinin cleavage was reduced, functionally active haemagglutinin and neuraminidase were absent and virions were not formed. In mutant-infected cells at 36 degrees C haemagglutinin cleavage was also reduced and virions formed had an altered NP:M ratio as well as a decreased haemagglutinin content. A population of virions formed under these conditions was heterogeneous both in morphology and in buoyant density. The data obtained suggest that a mutation in the M proteins of orthomyxoviruses can affect processing of the haemagglutinin and impair final stages of virion morphogenesis.

            Descriptors:  genes viral, genetic code, influenza A virus avian genetics, viral proteins genetics,  genetic complementation test, hemagglutinins viral genetics, microscopy, electron, mutation, neuraminidase genetics, RNA viral genetics, temperature, viral matrix proteins, virion genetics.

Ghendon, Y.Z., S.G. Markushin, A.T. Marchenko, B.S. Sitnikov, and V.P. Ginzburg (1973). Biochemical characteristics of fowl plague virus TS mutants. Virology 55(2): 305-19.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian growth and development, mutation, carbon radioisotopes, centrifugation, density gradient, chick embryo, DNA directed RNA polymerases metabolism, electrophoresis, polyacrylamide gel, genetic complementation test, hemagglutinins viral, influenza A virus avian enzymology, influenza A virus avian immunology, influenza A virus avian metabolism, neuraminidase biosynthesis, nucleoproteins biosynthesis,  peptide hydrolases metabolism, peptide synthesis, protein precursors biosynthesis, RNA viral biosynthesis, temperature, tissue culture, tritium, viral proteins biosynthesis,  virus replication.

Ghenkina, D.B. and Y.Z. Ghendon (1979). Recombination and complementation between orthomyxoviruses under conditions of abortive infection. Acta Virologica 23(2): 97-106.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  On interaction of ts mutants of fowl plague virus (FPV) belonging to different complementation groups and human influenza A viruses under conditions of abortive infection for both partners, complementation was marked and recombinants occurred with a high frequency. The level and degree of complementation as well as the frequency of recombinants depended on the stage at which the reproduction of the human influenza A viruses involved was blocked. On simultaneous inoculation of chicks with two apathogenic ts mutants of FPV belonging to different complementation groups, pathogenic ts+ recombinants appeared. On interaction of influenza B virus with ts mutants of FPV or ultraviolet-irradiated FPV, neither complementation nor recombination was observed. There was no complementation between influenza B virus and ts mutants of FPV even at the level of the formation of virus-specific substructures.

            Descriptors:  influenza A virus avian genetics, influenza A virus human genetics, mutation, orthomyxoviridae genetics, recombination, genetic,  chick embryo, genetic complementation test, influenza A virus avian growth and development, influenza A virus avian pathogenicity, influenza A virus human growth and development, tissue culture.

Giesendorf, B., F.X. Bosch, M. Orlich, C. Scholtissek, and R. Rott (1986). Studies on the temperature sensitivity of influenza A virus reassortants nonpathogenic for chicken. Virus Research 5(1): 27-42.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Influenza A virus reassortants which are nonpathogenic for chickens are like mammalian influenza A viruses in that they are temperature sensitive for growth at 41 degrees C. We have investigated the mechanism of this temperature sensitivity using reassortants between the two highly pathogenic strains A/FPV/Rostock/34 (FPV, H7N1) and A/turkey/England/63 (TE, H7N3). These reassortants show a strict correlation between the pathogenicity for chickens and the constellation of the genes coding for the ribonucleoprotein complex, RNP. Evidence is presented which shows that all viral components are synthesized in sufficient amounts and that the block in the viral replication cycle at the nonpermissive temperature is a late one affecting virus maturation. It is suggested that the RNP, although still enzymatically functional, may lose its ability to interact normally with viral surface components, thus interfering with the process of virus maturation. Some of the nonpathogenic reassortants which possessed the neuraminidase of TE showed an interesting temperature-dependent phenomenon: the haemagglutinin synthesized at the elevated temperature could only agglutinate erythrocytes at 20 degrees C, when the neuraminidase was inhibited or the infected cells vigorously disrupted by ultrasonication. This phenomenon is possibly not directly related to the temperature-sensitive block.

            Descriptors:  influenza A virus avian growth and development, chick embryo, chickens microbiology, genes viral, hemagglutination, viral, influenza A virus avian genetics, influenza A virus avian pathogenicity, influenza A virus avian physiology, neuraminidase metabolism, RNA viral biosynthesis, recombination, genetic, ribonucleoproteins genetics,  temperature, viral proteins biosynthesis, virus replication.

Ginzburg, V.P. (1975). Metod polucheniia monospetsificheskoi antisyvorotki k gemaggliutininu virusa chumy ptits [Method for preparing monospecific antiserum to fowl plague virus hemagglutinins]. Voprosy Virusologii (1): 100-2.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A simple method for preparation of monospecific antiserum for the hemagglutinin of fowl plague virus has been developed. It is based on selective inactivation of the enzymatic and antigenic properties of neuraminidase by heating of the virus at 56 degrees for 3 hours followed by disruption of the preparation with detergent and removal of the inner proteins by ultracentrifugation. Immunization of animals with such preparations produced antiserum containing considerable amounts of antibody for the hemagglutinin in the absence of antibody for other proteins of fowl plague virus.

            Descriptors:  hemagglutinins viral, immune sera, immunologic techniques, influenza A virus avian immunology.

Ginzburg, V.P., S.G. Markushin, and Y.Z. Ghendon (1982). Studies of biological properties of the recombinants between human influenza and fowl plague viruses as related to genome composition. Acta Virologica 26(6): 432-7.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Some biological properties of recombinants obtained by crossing of fowl plague and human influenza viruses were studied. The capacity of the recombinants to reproduce in chick embryo fibroblast cultures was in reverse correlation to the number of genes coding for P proteins derived from the human influenza virus. The genome composition was of importance for the expression of ts-phenotype of the recombinants in different systems. Substitution of at least one gene in the fowl plague virus genome by a corresponding human influenza virus gene resulted in the decrease of virulence for 1-day-old chickens. The presence of three P genes from human influenza virus genome in the genome of the recombinant proved to be insufficient for the capability of the recombinant to reproduce in organ cultures of human origin.

            Descriptors:  genes viral, influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic, cultured cells, chick embryo, chickens, influenza A virus avian pathogenicity, influenza A virus avian physiology, influenza A virus human pathogenicity, influenza A virus human physiology, nasal polyps microbiology, organ culture, plaque assay, temperature, virus replication.

Ginzburg, V.P., E.E. Rosina, O.K. Sharova, and Y.Z. Ghendon (1982). The replication of influenza A viruses in organ cultures of human nasal polyps. Archives of Virology 74(4): 293-8.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Organ cultures of human nasal polyps were shown to support the replication of five out of seven human influenza A viruses and three out of six avian strains with varying degrees of efficiency. The ability to replicate was independent of the antigenic formula of the virus. The structure of nasal polyps closely resembled that of normal nasal mucosa and infection with influenza A virus resulted in histological changes analogous to those seen in natural infections. This system provides an in vitro method for more detailed studies of influenza A virus and possibly other respiratory virus infections of man.

            Descriptors:  influenza microbiology, influenza A virus physiology, nasal polyps microbiology, virus replication, influenza A virus avian physiology, influenza A virus human physiology, organ culture, species specificity.

Ginzburg, V.P., E.E. Rozina, O.K. Sharova, and Y.U.Z. Ghendon (1985). Reproduction of human and animal influenza viruses in human nasal polyp organ cultures. Acta Virologica 29(5): 424-7.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Human influenza virus strains were easily grown and passaged in human nasal polyp organ cultures causing marked damage of the epithelium. Unlike to human strains, the animal influenza virus strain could be propagated for no longer than 2 or 3 passages and even the 1st passage failed to cause significant morphological changes of the epithelium cells.

            Descriptors:  influenza A virus avian growth and development, influenza A virus human growth and development, influenza A virus growth and development, nasal polyps microbiology, DNA replication, deer, influenza A virus genetics, nasal polyps pathology, organ culture, species specificity, virus replication.

Gitel'man, A.K., V.B. Martynenko, E.V. Molibog, N.K. Vorkunova, and A.G. Bukrinskaia (1976). Abortivnaia infektsiia virusa grippa v kletkakh astsitnogo raka Erlikha. Dal'neishee izuchenie svoistv astsitnogo virusa [Abortive influenza virus infection in Ehrlich ascitic cancer cells. Further studies of the properties of ascitic virus]. Voprosy Virusologii (6): 713-21.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Non-infectious virus particles produced by influenza virus (classical fowl plague)-infected Ehrlich ascitic carcinoma cells have the same morphology, size and sedimentation rate as the standard virions. Their main difference from the allantoic virus is their extreme fragility. They remain intact upon a short-term centrifugation in sucrose solutions but desintegrate upon prolonged centrifugation. In isopicnic fractionation they are detected in two forms, with a density of 1.23 g/ml retaining the hemagglutinating but not the neuraminidase activity and with a density of 1.27 g/ml deprived of both hemagglutinating and neuraminidase activity. In the electron microscopic examination the 1.23 g/ml structure appears as virus particles with defective areas in the surface spikes layer whereas the 1.27 g/ml structure has no spike layer at all. The protein analysis by polyacryl amide gel electrophoresis revealed a sharply reduced amount of the membrane protein in the ascitic virus. A hypothesis is suggested according to which the reduced amount of the membrane protein is the cause of the unusual fragility of ascitic virus particle membranes as a result of which they readily lose glycoproteins which, in its turn, leads to their reduced infectious activity.

            Descriptors:  carcinoma, Ehrlich tumor microbiology, influenza A virus avian isolation and purification, influenza A virus avian metabolism, cultured cells, centrifugation, centrifugation, density gradient, centrifugation, isopycnic, hemagglutinins viral analysis, microscopy, electron, neuraminidase metabolism, viral proteins analysis.

Gitelman, A.K. and A.G. Bukrinskaya (1971).  A comparison of influenza and parainfluenza and RNP properties. Archiv Fur Die Gesamte Virusforschung 34(2): 89-95.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian analysis, nucleoproteins analysis, parainfluenza virus 1, human analysis, buffers, carbon isotopes, centrifugation, density gradient, cesium, chick embryo, chlorides, hemagglutination tests, influenza A virus avian isolation and purification, nucleoproteins isolation and purification, parainfluenza virus 1, human isolation and purification, phosphates, phosphorus isotopes, precipitation, RNA, viral, species specificity, sucrose, surface active agents, trichloroacetic acid, virus cultivation.

Gitelman, A.K., A.V. Isachenko, and A.G. Bukrinskaya (1973). Sedimentation and buoyant density characteristics of influenza virus ribonucleoprotein. Acta Virologica 17(3): 257-60.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  nucleoproteins analysis, orthomyxoviridae analysis, viral proteins analysis, centrifugation, density gradient, cesium, chick embryo, chlorides, influenza A virus avian analysis, nucleoproteins isolation and purification, phosphorus isotopes, sucrose, tissue culture, tritium, viral proteins isolation and purification, virus cultivation.

Glathe, H., H.U. Strittmatter, M. Kunze, and H. Sinnecker (1982). Uber den Einfluss niedriger pH-Werte auf die Infektiositat und Neuraminidaseaktivitat menschlicher und tierischer Stamme des Influenzavirus Typ A. [Effect of low pH values on the infectivity and neuraminidase activity of human and animal strains of influenza virus type A]. Acta Biologica Et Medica Germanica 41(11): 1075-8.  ISSN: 0001-5318.

            NAL Call Number:  QH301.A25

            Abstract:  The influence of acidic pH on the infectivity and neuraminidase activity of human, equine and avian type A influenza virus strains has been studied. Following exposure to pH 3 human and equine strains lost their infectivity completely, whereas all investigated strains of the subtypes Hav6N2 and Hav7Neq2 retained a certain amount of infectivity. In contrast to human and equine strains the avian strains retained also 38% of their original neuraminidase activity after acidic treatment. Partial retention of infectivity and the relative stability of the neuraminidase following exposure to acidic pH are supposed to be linked together in avian influenza virus strains implicating neuraminidases for their ability to prevent the aggregation of virions.

            Descriptors:  influenza A virus human enzymology, influenza A virus enzymology, neuraminidase metabolism, hydrogen-ion concentration, influenza A virus avian enzymology, influenza A virus human pathogenicity, influenza A virus pathogenicity.

Goetschy, J.F., H. Zeller, J. Content, and M.A. Horisberger (1989). Regulation of the interferon-inducible IFI-78K gene, the human equivalent of the murine Mx gene, by interferons, double-stranded RNA, certain cytokines, and viruses. Journal of Virology 63(6): 2616-22.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The interferon-inducible gene (IFI-78K gene) that codes for a human protein, p78, of 78,000 Mr is the equivalent of the mouse Mx gene encoding Mx protein. The IFI-78K gene is located on chromosome 21 together with the alpha/beta interferon (IFN-alpha/beta) receptor. The p78 protein is important since it may be involved in resistance to influenza viruses. The regulation of the IFI-78K gene was studied in human diploid cells by using a cDNA probe to p78 mRNA and specific monoclonal antibodies to p78 protein. The IFI-78K gene, a normally quiescent gene, is transcriptionally regulated by IFN-alpha, and its induction does not require protein synthesis. The rate of transcription measured in a run-on assay increased rapidly but transiently. The level of p78 mRNA increased up to 8 h, declining slowly afterwards. The p78 protein, undetectable in untreated cells, accumulated up to 16 h, and its amount remained stable for at least 36 h after the addition of IFN-alpha. Cytokines such as tumor necrosis factor, interleukin-1 alpha, and interleukin-1 beta activated the IFI-78K gene at concentrations comparable to that of IFN-alpha. However, gene activation by these cytokines required protein synthesis. Poly(rI)-poly(rC) induced the IFI-78K gene directly at the transcriptional level without requirement for protein synthesis. Newcastle disease virus, influenza virus, and to a lesser extent vesicular stomatitis virus also induced the IFI-78K gene in the absence of any protein synthesis. Induction of transcription by viruses was markedly enhanced by pretreatment of cells with IFN-gamma (which by itself is a poor inducer of the IFI-78K gene), resulting in accumulation of p78 protein during the course of infection; this suggests that IFN-gamma programs cells to full antiviral activity upon virus infection.

            Descriptors:  chromosomes, human, pair 21, GTP binding proteins, gene expression regulation, proteins genetics, blotting, northern, blotting, western, influenza A virus avian physiology, interferon type I, recombinant pharmacology, interferon gamma, recombinant pharmacology, interleukin 1 pharmacology, Newcastle disease virus physiology, RNA, double stranded pharmacology, recombinant proteins pharmacology, transcription, genetic, translation, genetic, tumor necrosis factor pharmacology, vesicular stomatitis Indiana virus physiology.

Goncharskaia, T.I.A. (1978). Eksperimental'noe izuchenie protivovirusnykh svoistv antibiotika  6734-21. [Experimental study of the antiviral properties of antibiotic 6734-21]. Antibiotiki  23(1): 58-62.  ISSN: 0003-5637.

            NAL Call Number:  396.8 An84

            Abstract:  The effect of antibiotic 6734-21 on the viruses of variolovaccine, Herpes simplex, influenza and classical avian plague was studied on various experimental models. Antibiotic 6734-21 inhibited development of the variolovaccine virus in the tissue culture, in chick embryos, in rabbits with variolovaccine infection, as well as the development of the viruses of Herpes simplex, Aueski, and Newcastle diseases in the tissue culture. It had a virulicidic effect on the viruses of variolovaccine, influenza and classical avian plague.

            Descriptors:  anti bacterial agents pharmacology, antiviral agents, anti bacterial agents therapeutic use, chick embryo, herpes simplex drug therapy, herpesvirus 1, suid drug effects, influenza A virus avian drug effects, influenza A virus drug effects, mice, Newcastle disease virus drug effects, rabbits, simplexvirus drug effects, smallpox drug therapy, variola virus drug effects.

Goncharskaia, T.I.A., S.M. Navashin, S.L. Grokhovskii, and A.L. Zhuze (1977). Izuchenie protivovirusnykh svoistv analogov distamitsina A. [Antiviral properties of analogs of distamycin A]. Antibiotiki  22(11): 998-1002.  ISSN: 0003-5637.

            NAL Call Number:  396.8 An84

            Abstract:  The effect of 9 analogues of distamycin A was studied in a tissue culture with respect to the virus of a smallpox vaccine and classical avian plague. Three analogues of distamycin A (I, VI, VII) were studied in chick embryos with respect to the smallpox and influenza viruses. The analogues were characterized by a loss or decrease of the activity against the smallpox vaccine virus as compared to distamycin A. In contrast to distamycin A analogue VII had an inhibitory effect on influenza infection in chick embryos.

            Descriptors:  antiviral agents, distamycins pharmacology, influenza A virus avian drug effects, orthomyxoviridae drug effects, pyrroles pharmacology, variola virus drug effects.

Gonzalez Salazar, V.D.,  A. Hernandez Magdaleno, J.I. Monroy Basilio, H. Rodriguez Velazco, and J. Garcia Garcia. (1996). Avances sobre la distribucion de la replicacion de diferentes cepas del virus de la influenza aviar en embrion de pollo y aves por histopatologia e inmunohistoquimica. [Distribution of avian influenza virus in chickens and chick embryos by histopathology and immunihistochemistry]. In: Reunion Nacional de Investigacion Pecuaria, Cuernavaca, Morelos, (Mexico), p. 136.

            Abstract: El objetivo fue analizar mediante histopatologia e inmunohistoquimica (IH), el tipo de lesiones y el patron de infectividad que producen en el embrion de pollo y aves al inocular los aislamientos del virus de influenza aviar (IA), provenientes de diferentes zonas del pais. Como cepas de IA de alta patogenicidad, se utilizaron los aislamientos Queretaro y Puebla y como cepa de baja patogenicidad, la cepa vacunal.

            Descriptors: avian influenza virus, infection, histopathology, disease transmission, influenza virus, orthomyxoviridae, pathogenesis, pathology, viruses.

Gorman, O.T., W.J. Bean, Y. Kawaoka, and R.G. Webster (1990). Evolution of the nucleoprotein gene of influenza A virus. Journal of Virology 64(4): 1487-97.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Nucleotide sequences of 24 nucleoprotein (NP) genes isolated from a wide range of hosts, geographic regions, and influenza A virus serotypes and 18 published NP gene sequences were analyzed to determine evolutionary relationships. The phylogeny of NP genes was determined by a maximum-parsimony analysis of nucleotide sequences. Phylogenetic analysis showed that NP genes have evolved into five host-specific lineages, including (i) Equine/Prague/56 (EQPR56), (ii) recent equine strains, (iii) classic swine (H1N1 swine, e.g., A/Swine/Iowa/15/30) and human strains, (iv) gull H13 viruses, and (v) avian strains (including North American, Australian, and Old World subgroups). These NP lineages match the five RNA hybridization groups identified by W. J. Bean (Virology 133:438-442, 1984). Maximum nucleotide differences among the NPs was 18.5%, but maximum amino acid differences reached only 10.8%, reflecting the conservative nature of the NP protein. Evolutionary rates varied among lineages; the human lineage showed the highest rate (2.54 nucleotide changes per year), followed by the Old World avian lineage (2.17 changes per year) and the recent equine lineage (1.22 changes per year). The per-nucleotide rates of human and avian NP gene evolution (1.62 x 10(-3) to 1.39 x 10(-3) changes per year) are lower than that reported for human NS genes (2.0 x 10(-3) changes per year; D. A. Buonagurio, S. Nakada, J. D. Parvin, M. Krystal, P. Palese, and W. M. Fitch, Science 232:980-982, 1986). Of the five NP lineages, the human lineage showed the greatest evolution at the amino acid level; over a period of 50 years, human NPs have accumulated 39 amino acid changes. In contrast, the avian lineage showed remarkable conservatism; over the same period, avian NP proteins changed by 0 to 10 amino acids. The specificity of the H13 NP in gulls and its distinct evolutionary separation from the classic avian lineage suggests that H13 NPs may have a large degree of adaptation to gulls. The presence of avian and human NPs in some swine isolates demonstrates the susceptibility of swine to different virus strains and supports the hypothesis that swine may serve as intermediates for the introduction of avian influenza virus genes into the human virus gene pool. EQPR56 is relatively distantly related to all other NP lineages, which suggests that this NP is rooted closest to the ancestor of all contemporary NPs. On the basis of estimation of evolutionary rates from nucleotide branch distances, current NP lineages are at least 100 years old, and the EQPR56 NP is much older.(ABSTRACT TRUNCATED AT 400 WORDS)

            Descriptors:  evolution, genes viral, influenza A virus genetics, nucleoproteins genetics, viral proteins genetics, adaptation, biological, amino acid sequence, base sequence, cloning, molecular, DNA, viral analysis, influenza A virus classification, molecular sequence data, phylogeny, software, species specificity.

Goto, H. (2004). [Novel function of plasminogen-binding activity of the NA determines the pathogenicity of influenza A virus]. Uirusu Journal of Virology 54(1): 83-91.  ISSN: 0042-6857.

            Abstract:  Because cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for infectivity of influenza A viruses, this molecule is a major determinant of viral pathogenicity. Although well documented in the pathogenicity of avian influenza viruses, the role of HA cleavage in the pathogenicity of mammalian viruses is not well understood. Therefore, we studied a mouse-adapted human isolate A/WSN/33 (WSN), a neurovirulent influenza virus strain that causes systemic infection when inoculated intranasally into mice. We found a novel mechanism of HA cleavage for WSN virus: the neuraminidase (NA) of WSN virus binds and sequesters plasminogen on the cell surface, leading to enhanced cleavage of the HA. The structural basis of this novel function of the NA molecule appears to be the presence of a carboxyl-terminal lysine and the absence of an oligosaccharide side chain at position 146. To obtain direct evidence that the plasminogen-binding activity of the NA enhances the pathogenicity of WSN virus, we generated mutant viruses that are deficient in plasminogen-binding activity by reverse genetics. The mutant viruses showed attenuated growth in mice and failed to grow at all in the brains of these animals. Therefore, we concluded that the novel function of plasminogen-binding activity of the NA determines the pathogenicity of WSN virus in mice.

            Descriptors:  influenza A virus enzymology, influenza A virus pathogenicity, neuraminidase metabolism, plasminogen metabolism, virulence, hemagglutinins metabolism, mice, neuraminidase chemistry, protein binding.

Govorkova, E.A., A.S. Gambaryan, E.C. Claas, and Y.A. Smirnov (2000). Amino acid changes in the hemagglutinin and matrix proteins of influenza a (H2) viruses adapted to mice. Acta Virologica 44(5): 241-8.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Mouse-adapted (MA) variants of human and avian influenza A (H2) viruses were generated and characterized with respect to acquisition of virulence in mice. From the nucleotide sequence the amino acid sequence was deduced. The HA1 subunit of the hemagglutinin (HA) contained three amino acid substitutions in the A/black duck/New Jersey/1580/78-MA variant (Glu216-->Asp, Lys307-->Arg, and Thr318-->Ile) and two substitutions in the A/JapanxBellamy/57-MA variant (Lys25-->Thr and Ser203-->Phe). In the M1 protein, there were two substitutions in the A/black duck/New Jersey/1580/78-MA variant (Asn30-->Asp and Gln214-->His) and a single substitution in the A/JapanxBellamy/57-MA variant (Met179-->Lys). The M2 protein amino acid sequences of the parental virus and the MA variants differed by a single identical mutation (Asn93-->Ser). The localization and atomic distances of the observed mutations on the three-dimensional (3D) structure of the HA protein were analyzed for influenza H2 viruses. The obtained results were similar to those published earlier on H1, H3 and H5 subtypes. The amino acid changes in the HA protein could be divided into two groups. In one group the substitutions were situated at the top of the molecule, while in the other group they were clustered in the stem area at the interface region between three HA monomers. The analysis revealed that the substitutions observed in the MA variants probably increase the flexibility of the HA molecule and/or weaken the interactions between monomers or subunits in the HA trimer. The relationships of the observed amino acid changes in the HA and M proteins to the biological properties of the respective viruses and possible mechanisms involved in the acquisition of viral virulence are discussed.

            Descriptors:  bacterial outer membrane proteins, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, influenza A virus human genetics, viral matrix proteins genetics, amino acid substitution, bacterial proteins chemistry, bacterial proteins genetics, birds, carrier proteins chemistry, carrier proteins genetics, cell line, chick embryo, hemagglutinin glycoproteins, influenza virus chemistry, influenza A virus avian pathogenicity, influenza A virus human pathogenicity, lung virology, mice, viral matrix proteins chemistry.

Govorkova, E.A., V.M. Kibardin, A.A. Kizina, G.M. Nazarova, and I.U.A. Smirnov (1991). Vzaimosviazi virusov grippa A(H2) cheloveka i ptits, opredeliaemye matematicheskoi obrabotkoi dannykh ob antigennoi strukture gemagglutinina. [The interrelations of the human and avian influenza viruses A(H2) determined by the mathematical processing of data on the antigenic structure of their hemagglutinin]. Voprosy Virusologii 36(6): 463-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Mathematical methods were used to analyse the data on the antigenic specificity of H2 subtype hemagglutinin of human and avian influenza A viruses. This approach allowed the evaluation of possible evolutional relationships in this little-studied group of viruses. Influenza A (H2) viruses isolated from birds in the USA were found to represent a sufficiently isolated group, whereas European avian strains (A/duck/Germany/1215/73, A/pintail duck/Primor'e/695/76, A/duck/Marseilles/46/76) were close to "human" viruses. The A/Leningrad/1468/65, A/laughing gull/New Jersey/75/85, and A/pintail duck/Alberta/2728/77 strains represent marked antigenic variants apparently rather far gone as a result of hemagglutinin drift.

            Descriptors:  antigens, viral immunology, hemagglutinins viral immunology, influenza A virus avian immunology, influenza A virus human immunology, algorithms, antigenic variation immunology, antigens, viral classification, cluster analysis, ducks microbiology, evolution, hemagglutinins viral classification, influenza A virus avian classification, influenza A virus human classification.

Govorkova, E.A., J.E. Rehg, S. Krauss, H.L. Yen, Y. Guan, M. Peiris, T.D. Nguyen, T.H. Hanh, P. Puthavathana, H.T. Long, C. Buranathai, W. Lim, R.G. Webster, and E. Hoffmann ( 2005). Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. Journal of Virology 79(4): 2191-8.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets. The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chicken/Vietnam/C58/04 and A/quail/Vietnam/36/04 viruses. Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.

            Descriptors:  influenza virus infection, respiratory system disease, viral disease complications, etiology, mortality, pathology, transmission, Vietnam, Thailand, ferrets, chickens, humans.

Govorkova, E.A. and Y.U.A. Smirnov (1997). Cross-protection of mice immunized with different influenza A (H2) strains and challenged with viruses of the same HA subtype. Acta Virologica 41(5): 251-7.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Cross-protection of mice immunized with inactivated preparations of human and avian influenza A (H2) viruses was determined after lethal infection with mouse-adapted (MA) variants of human A/Jap x Bell/57 (H2N1) and avian A/NJers/78 (H2N3) viruses. The MA variants differed from the original strains by acquired virulence for mice and changes in the HA antigenicity. These studies indicated that mice vaccinated with human influenza A (H2) viruses were satisfactorily protected against challenge with A/Jap x Bell/57-MA variant; the survival rate was in the range of 61%-88.9%. Immunization of mice with the same viral preparations provided lower levels of protection against challenge with A/NJers/78-MA variant. Vaccination of mice with the avian influenza A (H2) viruses induced better protection than with human strains against challenge with both MA variants. Challenge with A/NJers/78-MA variant revealed that 76.2%-95.2% of animals were protected when vaccinated with avian influenza virus strains isolated before 1980, and that the protection reached only 52.4%-60.0% in animals vaccinated with strains isolated in 1980-1985. The present study revealed that cross-protection experiments in a mouse model could provide necessary information for the development of appropriate influenza A (H2) virus vaccines with a potential for these viruses to reappear in a human population.

            Descriptors:  influenza prevention and control, influenza A virus avian immunology, influenza A virus human immunology, influenza vaccine immunology, cross reactions, disease models, animal, influenza mortality, influenza A virus avian classification, influenza A virus avian pathogenicity, influenza A virus human classification, influenza A virus human pathogenicity, mice, vaccination, vaccines, attenuated immunology.

Grambas, S., M.S. Bennett, and A.J. Hay (1992). Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. Virology 191(2): 541-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Mutations in the influenza M2 membrane protein which confer resistance to the antiviral drug amantadine are exclusively located within the transmembrane region of the molecule. The influence of specific amino acid substitutions on the activity of the M2 protein in influenza A virus-infected cells is assessed in this report by their effects upon haemagglutinin (HA) stability and virus growth. A number of amino acid substitutions, e.g., L26H, A30T, S31N and G34E reduced the activity of the M2 protein of A/chicken/Germany/34 (Rostock) and caused a substantial increase in expression of the low-pH form of HA. The adverse effects of the mutations on virus replication were evident from changes selected during subsequent passage of the mutant viruses in the presence or absence of amantadine: reversion to wt, the acquisition of a second suppressor mutation in M2, or the appearance of a complementary mutation in HA which increased its pH stability. In contrast, 127T and 127S, mutations which were most readily selected following passage of the wt virus in the presence of drug, caused an increase in M2 activity. Furthermore, in double mutants the 127T mutation suppressed the attenuating effects of the A30T and S31N mutations on M2 activity. The influence of primary structure on the consequences of particular amino acid changes was further emphasized by the contrasting effects of the G34E mutation on the activities of two closely related proteins, causing an increase in the activity of the M2 of A/chicken/Germany/27 (Weybridge) as opposed to the decrease in activity of the Rostock protein. Estimates of differences in trans Golgi pH based on the degree of conversion of HA to the low-pH form, or complementation of differences in pH stability of mutant HAs, indicate that changes in M2 may influence pH within the transport pathway by as much as 0.6. The results thus provide further evidence that M2 regulates transmembrane pH gradients in the trans Golgi. Incompatibility between particular HA and M2 components and the selection of M2 mutants with suboptimal activity stresses the essential relationship between the structures and functions of these two virus proteins.

            Descriptors:  amantadine pharmacology, influenza A virus avian metabolism, viral matrix proteins drug effects, viral matrix proteins genetics, water electrolyte balance genetics, amino acid sequence, drug resistance, microbial, genetic complementation test, hemagglutinins viral biosynthesis, hydrogen-ion concentration, influenza A virus avian growth and development, molecular sequence data, mutagenesis, mutation, structure activity relationship, variation genetics.

Gribkova, N.V., N.V. Kaverin, I.V. Tsvetkova, and M.A. Lipkind (1973). Occurence of unstability of hemagglutinin and neuraminidase in cells infected with different myxoviruses. Archiv Fur Die Gesamte Virusforschung 43(1): 98-102.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  hemagglutinins viral, influenza A virus avian immunology, neuraminidase metabolism, Newcastle disease virus enzymology, Newcastle disease virus immunology, orthomyxoviridae immunology, chick embryo, cycloheximide pharmacology, drug stability, fetal membranes, influenza A virus avian enzymology, influenza A virus avian growth and development, Newcastle disease virus growth and development, orthomyxoviridae enzymology, orthomyxoviridae growth and development, tissue culture.

Gribkova, N.V., N.F. Kazak, and V.I. Votyakov (1984). Development of resistance to 2-(1-amino-ethyl)-bicyclo (2.2.1) heptane chlorohydrate in influenza A virus. Acta Virologica 28(1): 69-72.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  A resistant influenza virus has been obtained during successive passages of influenza A virus in 10 to 11-day-old chick embryos (CE) in the presence of 2-(1'-amino-ethyl)-bicyclo(2.2.1) heptane chlorohydrate possessing a high antiviral activity. The virus resistance to the inhibitor was not lost after one passage in the absence of the drug.

            Descriptors:  antiviral agents pharmacology, influenza A virus avian drug effects, norbornanes pharmacology, drug resistance, microbial, virus replication drug effects.

Grinev, A.A., N.A. Petrov, S.I.A. Golovin, L.V. Mamaev, and T.P. Mikriukova (1988). Pervichnaia struktura polnorazmernoi DNK-kopii gena neiraminidazy antigennogo podtipa N7 virusa grippa ptits. [Primary structure of the full-length DNA copy of the neuraminidase gene in the avian influenza virus of the N7 antigenic subtype]. Bioorganicheskaia Khimiia 14(3): 416-8.  ISSN: 0132-3423.

            NAL Call Number:  QD415.A1S62

            Abstract:  Complete nucleotide sequence of the cloned full-length DNA copy of the influenza virus A/FPV Weybridge (H7N7) neuraminidase gene has been determined.

            Descriptors:  base sequence, DNA, viral genetics, genes viral, influenza A virus avian genetics, neuraminidase genetics, sequence homology, nucleic acid, antigens, viral analysis, cloning, molecular, DNA genetics, influenza A virus avian classification, influenza A virus avian enzymology, molecular sequence data.

Guan, Y., K.F. Shortridge, S. Krauss, P.S. Chin, K.C. Dyrting, T.M. Ellis, R.G. Webster, and M. Peiris (2000). H9N2 influenza viruses possessing H5N1-like internal genomes continue to circulate in poultry in southeastern China. Journal of Virology 74(20): 9372-80.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The transmission of H9N2 influenza viruses to humans and the realization that the A/Hong Kong/156/97-like (H5N1) (abbreviated HK/156/97) genome complex may be present in H9N2 viruses in southeastern China necessitated a study of the distribution and characterization of H9N2 viruses in poultry in the Hong Kong SAR in 1999. Serological studies indicated that H9N2 influenza viruses had infected a high proportion of chickens and other land-based birds (pigeon, pheasant, quail, guinea fowl, and chukka) from southeastern China. Two lineages of H9N2 influenza viruses present in the live-poultry markets were represented by A/Quail/Hong Kong/G1/97 (Qa/HK/G1/97)-like and A/Duck/Hong Kong/Y280/97 (Dk/HK/Y280/97)-like viruses. Up to 16% of cages of quail in the poultry markets contained Qa/HK/G1/97-like viruses, while about 5% of cages of other land-based birds were infected with Dk/HK/Y280/97-like viruses. No reassortant between the two H9N2 virus lineages was detected despite their cocirculation in the poultry markets. Reassortant viruses represented by A/Chicken/Hong Kong/G9/97 (H9N2) were the major H9N2 influenza viruses circulating in the Hong Kong markets in 1997 but have not been detected since the chicken slaughter in 1997. The Qa/HK/G1/97-like viruses were frequently isolated from quail, while Dk/HK/Y280/97-like viruses were predominately associated with chickens. The Qa/HK/G1/97-like viruses were evolving relatively rapidly, especially in their PB2, HA, NP, and NA genes, suggesting that they are in the process of adapting to a new host. Experimental studies showed that both H9N2 lineages were primarily spread by the aerosol route and that neither quail nor chickens showed evidence of disease. The high prevalence of quail infected with Qa/HK/G1/97-like virus that contains six gene segments genetically highly related to HK/156/97 (H5N1) virus emphasizes the need for surveillance of mammals including humans.

            Descriptors:  genome, viral, influenza A virus avian isolation and purification, poultry virology, China, hemagglutination inhibition tests, influenza A virus avian genetics, phylogeny, temperature, virus replication.

Gubareva, L.V., R. Bethell, G.J. Hart, K.G. Murti, C.R. Penn, and R.G. Webster (1996). Characterization of mutants of influenza A virus selected with the neuraminidase inhibitor 4-guanidino-Neu5Ac2en. Journal of Virology 70(3): 1818-27.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The development of viral resistance to the neuraminidase (NA) inhibitor, 4-guanidino-Neu5Ac2en, of influenza viruses was studied by serial passage of A/Turkey/Minnesota/833/80 (H4N2) in Madin-Darby canine kidney cells in the presence of increasing concentrations of inhibitor. Resistant mutants selected after eight passages, had a 10,000-fold reduction in sensitivity to the inhibitor in plaque assays, but their affinity (1/Kd) to the inhibitor was similar to that of the parental virus. Electron microscopic analysis revealed aggregation of the mutant virus at the cell surface in the presence of the inhibitor. Sequence analysis established that a substitution had occurred in the NA (Arg-249 to Lys) and in the HA2 subunit of the hemagglutinin (Gly-75 to Glu), in the vicinity of the proposed second sialic acid binding site. The change of residue 249 appears to be a chance mutation, for we were unable to reisolate this mutant, whereas subsequent experiments indicate changes in the hemagglutinin. After 13 passages of the parental virus, mutants that were resistant to the high concentrations of inhibitor tested were obtained. These viruses retained their drug-resistant phenotype even after five passages without the inhibitor. Electron microscopic analysis revealed no aggregation of virus on the surface of infected cells in the presence of the inhibitor. Sequence analysis of the NA gene from these drug-resistant mutants revealed an additional substitution of Glu to Ala at the conserved amino acid residue 119. This substitution is responsible for reducing the affinity of the inhibitor to the NA. Our findings suggest that the emergence of mutants resistant to 4-guanidine-Neu5Ac2en is a multistep process requiring prolonged exposure to the inhibitor.

            Descriptors:  antiviral agents pharmacology, enzyme inhibitors pharmacology, influenza A virus avian drug effects, mutation, neuraminidase antagonists and inhibitors, sialic acids pharmacology, base sequence, cell line, DNA, viral, dogs, drug resistance, microbial genetics, influenza A virus avian enzymology, influenza A virus avian genetics, influenza A virus avian ultrastructure, molecular sequence data, neuraminidase chemistry, turkeys virology.

Gubareva, L.V., J.A. McCullers, R.C. Bethell, and R.G. Webster (1998). Characterization of influenza A/HongKong/156/97 (H5N1) virus in a mouse model and protective effect of zanamivir on H5N1 infection in mice. Journal of Infectious Diseases 178(6): 1592-6.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  A recent outbreak of influenza in Hong Kong was caused by a highly virulent virus of avian origin. Concern that the appearance of such a virus in the human population may be a harbinger of a new pandemic has brought increased attention to the issue of antivirals available for treatment of influenza. A/HongKong/156/97 (H5N1), the first virus of H5N1 subtype isolated from a human host, is highly virulent in the mouse model and can infect mouse lungs without requiring adaptation. High mortality and evidence of systemic disease, including spread to the brain after intranasal inoculation, are observed. Zanamivir, a novel neuraminidase inhibitor, is effective at decreasing replication of the virus in vitro. In a model of lethal challenge in mice, Zanamivir reduces lung titers of the virus and decreases morbidity and mortality.

            Descriptors:  antiviral agents therapeutic use, influenza prevention and control, influenza A virus avian physiology, sialic acids therapeutic use, chick embryo, Hong Kong, influenza physiopathology, influenza A virus avian drug effects, influenza A virus avian isolation and purification, influenza A virus avian pathogenicity, influenza A virus human, lung virology, mice, mice inbred BALB c, organ specificity, virulence, virus replication drug effects.

Gubareva, L.V., C.R. Penn, and R.G. Webster (1995). Inhibition of replication of avian influenza viruses by the neuraminidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid. Virology 212(2): 323-330.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The sialidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid(4-guanidino-Neu5Ac2en), designed with computer assistance and knowledge of the crystal structure of influenza virus neuraminidase, has shown antiviral effects in animal models of human influenza (M. von Itzstein et al., Nature, 363, 418-423, 1993). Here we demonstrate that the compound efficiently inhibits the enzyme activity of all nine subtypes of avian influenza A neuraminidase in vitro. When administered intranasally to chickens infected with lethal viruses, high doses of the compound (1000 microgram/kg) protected 85% of birds harboring A/Chick/Victoria/1/85 (H7N7), a fowl plague virus, but not chickens infected with other highly virulent viruses of the N1, N2, or N3 subtype. This differential inhibitory effect was also seen in a plaque reduction assay with Madin-Darby canine kidney cells (MDCK), where 4-guanidino-Neu5Ac2en was more effective against A/Chick/Vic/85 (H7N7) than A/FPV/Rostock/34 (H7N1). In contrast to the substantial plaque reduction observed in MDCK cells, the drug failed to inhibit plaque formation in chicken embryo fibroblasts infected with either A/Chick/Vic/85 or A/FPV/Rostock/34, regardless of its concentration. The different levels of drug efficacy seen in two cell systems most likely reflect the location of virus budding and release in polarized versus nonpolarized cells, as well as the compound's mode of extracellular action.

            Descriptors:  avian influenza virus, glycosidases, enzyme inhibitors, enzymic activity, inhibition, animal models, influenza virus, mankind, antimetabolites, chemicophysical properties, enzymes, hydrolases, influenza virus, orthomyxoviridae, viruses, sialidase.

Guo, C.T., S. Ohta, A. Yoshimoto, K. Nakata, K.F. Shortridge, T. Takahashi, T. Suzuki, D. Miyamoto, K.I. Jwa Hidari, and Y. Suzuki (2001). A unique phosphatidylinositol bearing a novel branched-chain fatty acid from Rhodococcus equi binds to influenza virus hemagglutinin and inhibits the infection of cells. Journal of Biochemistry 130(3): 377-84.  ISSN: 0021-924X.

            NAL Call Number:  385 J822

            Abstract:  From the aquatic bacterium Rhodococcus equi strain S(420), we isolated a substance that strongly binds to influenza viruses. Structural analyses revealed that it is a unique type of phosphatidylinositol (PtdIns) bearing a branched-chain fatty acid (14-methyloctadecanoic acid). In a TLC/virus-binding immunostaining assay, this PtdIns bound to all subtypes of hemagglutinin (HA) of influenza A viruses tested, isolated from humans, ducks and swine, and also to human influenza B viruses. Furthermore, the PtdIns significantly prevented the infection of MDCK cells by influenza viruses, and also inhibited the virus-mediated hemagglutination and low pH-induced hemolysis of human erythrocytes, which represents the fusogenic activities of the viral HA. We also used purified hemagglutinin instead of virions to examine the interaction between viral HA and PtdIns, showing that the PtdIns binds to hemagglutinin. These findings indicate that the inhibitory mechanism of PtdIns on the influenza virus infection may be through its binding to viral HA spikes and host cell endosomal/lysosomal membranes, which are mediated by the function of viral HA.

            Descriptors:  hemagglutinins viral metabolism, influenza prevention and control, influenza A virus human metabolism, phosphatidylinositols metabolism, phosphatidylinositols pharmacology, Rhodococcus equi, binding sites physiology, cultured cells, dogs, ducks, fatty acids chemistry, hemagglutination drug effects, hemolysis drug effects, influenza A virus avian metabolism, influenza A virus, porcine metabolism, influenza B virus chemistry, kidney cytology, orthomyxoviridae metabolism, phosphatidylinositols isolation and purification, swine.

Guo, X., M. Liao, and C. Xin (2003). Sequence of HA gene of avian influenza A/Chicken/Guangdong/SS/1994 (H9N2) virus. Avian Diseases 47(Special Issue): 1118-1121.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The RNA of the hemagglutinin (HA) gene of A/Chicken/Guangdong/SS/1994 (H9N2) was reverse transcription-polymerase chain reaction amplified, and the cDNA was cloned into a plasmid vector. The complete coding sequence of the HA gene was sequenced and included 1683 nucleotides, which encoded for a protein of 560 amino acids. The potential glycosylation sites related to HA protein function were highly conserved. The amino acid sequence of the HA proteolytic cleavage was G-S-S-R/G. This cleavage site sequence is compatible with a low-pathogenic avian influenza virus. Sequence comparison of this HA gene with other H9 influenza virus sequences in the GenBank database showed a 82%-97% nucleotide and amino acid sequence similarity.

            Descriptors:  infection, virology, avian influenza, infectious disease, respiratory system disease, viral disease, cloning genetic techniques, laboratory techniques, reverse transcriptase polymerase chain reaction, RT PCR, genetic techniques, protein function sequence similarity.

Guo, Y., M. Wang, and J. Guo (1999). [The complete nucleotide sequences of A/Goose/Guangdong/2/96(H5N1) virus RNA segment 1-3 and 5]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi Zhonghua Shiyan He Linchuang Bingduxue Zazhi [Chinese Journal of Experimental and Clinical Virology]. 13(3): 205-8.  ISSN: 1003-9279.

            Abstract:  OBJECTIVE: To determine the nucleotide and amino acid sequences of PB2, PB1, PA and NP genes and compared them with sequences of A/HK/156/97(H5N1) virus for revealing the relationship between A/Googs/Guangdong/2/96(H5N1) and A/HK/156/97(H5N1) viruses. METHODS: Virion RNA was transcribed into cDNA by reverse transcriptase, cDNA amplified by PCR, the productions of PCR were purified. Afterward, RNA sequence analysis was performed by the dideoxynucleotide chain termination method, using synthetic oligodeoxynucleotide primers. RESULTS: The lengths of A/Goose/Guangdong/2/96(H5N1) virus RNA segment 1-3 and 5 contain 2,341, 2,341, 2,233 and 1,565 nucleotides, respectively. They encode for PB2 (759 amino acids), PB1 (757 amino acids), PA (716 amino acids) and NP (498 amino acids) proteins. The homologies of amino acid sequences of PB2, PB1, PA and NP proteins between A/Goose/Guangdong/2/96 (H5N1) and A/HK/156/97 (H5N1) virus are 96.4%, 97.2%, 97.3% and 97.0%, respectively. CONCLUSION: The lengths of RNA segment 1-3 and 5 of Goose strain are 2,341, 2,341, 2,233 and 1,565 nucleotides, respectively. The nucleotide sequences of these genes are distinguish able from those of Hong Kong virus.

            Descriptors:  geese virology, influenza A virus avian genetics, poultry diseases virology, RNA viral genetics, amino acid sequence, influenza A virus avian classification, influenza A virus avian isolation and purification,  molecular sequence data, sequence analysis, RNA.

Guo, Y., M. Wang, and X. Xu (1999). [Nucleotide sequence of A/Goose/Guangdong/2/96 (H5N1) virus M and NS RNA]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi Zhonghua Shiyan He Linchuang Bingduxue Zazhi [Chinese Journal of Experimental and Clinical Virology]. 13(4): 305-8.  ISSN: 1003-9279.

            Abstract:  OBJECTIVE: To determine the nucleotide sequences of M and NS genes of A/Goose/Guangdong/2/96(H5N1) virus and also to compare them with the sequences of A/HK/156/97(H5N1) strain for revealing the relationship between the two viruses, as well as for setting up a solid base for studying M and NS genes of influenza A viruses in the future. METHODS: Virion RNA was transcribed into cDNA by reverse transcriptase, cDNA was amplified by PCR, the products of PCR were purified. Afterward, RNA sequence analysis was performed by the dideoxynucleotide chain termination method using synthetic oligodeoxynucleotide primers. RESULTS: The segment length of A/Goose/Guangdong/2/96(H5N1) virus RNA 7 is 1,027 nucleotides. It codes M1 (252 amino acids) and M2 (97 amino acids) proteins. However, the segment length of RNA 8 of A/Goose/Guangdong/2/96(H5N1) virus is 890 nucleotides coding NS1 (230 amino acids) and NS2 (121 amino acids) proteins. The amino acid sequence homologies of M1, M2, NS1 and NS2 protein molecules between A/Goose/Guangdong/2/9(H5N1) and A/HK/156/97 (H5N1) viruses are 97.6%, 92.8%, 65.7% and 76.9%, respectively. CONCLUSION: The lengths of A/Goose/Guangdong/2/96(H5N1) virus RNA 7 and RNA 8 and 1,027 are 890 nucleotides, respectively. These two RNA segments belong to those of avian influenza A virus. The A/HK/156/97(H5N1) virus RNA 7 and RNA 8 segments are not derived from those of A/Goose/Guangdong/2/96(H5N1) virus directly.

            Descriptors:  nucleotide sequence, influenza A virus, goose, Guangdong, RNA.

Guo, Y., M. Wang, G.S. Zheng, W.K. Li, Y. Kawaoka, and R.G. Webster (1995). Seroepidemiological and molecular evidence for the presence of two H3N8 equine influenza viruses in China in 1993-94. Journal of General Virology 76(Pt. 8): 2009-14.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  In May 1993, a severe epidemic of respiratory disease began in horses in Inner Mongolia and spread throughout horses in China. The disease affected mules and donkeys as well as horses but did not spread to other species, including humans. The severity of the disease raised the question of whether the outbreak might have been caused by the new avian-like influenza viruses detected in horses in China in 1989 or by current variants ofA/equine/Miami/1/63 (H3N8) (equine-2) or by a reassortant between these viruses. Antigenic and sequence analysis established that all gene segments of the influenza virus causing the epidemic were of recent equine-2 origin and that the virus was not a reassortant. Serological analysis of post-infection horse sera provided evidence for the continued circulation of the A/Equine/Jilin/1/89 (Eq/Jilin) (H3N8) avian-like viruses in horses in Heilongjiang province with original antigenic sin-like responses. It is noteworthy that prior infection with the avian-like Eq/Jilin strain did not afford cross-protection against a current equine-2 strain. Serological evidence for the continued circulation of the avian-like H3N8 influenza virus in horses indicates that this virus has probably established itself in horses in Asia.

            Descriptors:  horse diseases epidemiology, influenza veterinary, influenza A virus genetics, antibodies, viral blood, antigens, viral immunology, base sequence, China epidemiology, disease outbreaks veterinary, genome, viral,  horse diseases virology, horses, influenza epidemiology, influenza virology, influenza A virus classification, influenza A virus immunology, molecular sequence data, phylogeny, sequence analysis, DNA, sequence homology, nucleic acid, seroepidemiologic studies, serotyping.

Guo, Y., X. Xu, and X. Wan (1998). [Genetic characterization of an avian influenza A (H5N1) virus isolated from a sick goose in China]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi Zhonghua Shiyan He Linchuang Bingduxue Zazhi [Chinese Journal of Experimental and Clinical Virology]. 12(4): 322-5.  ISSN: 1003-9279.

            Abstract:  Genetic analysis of viral HA gene showed that there were 22 nucleotide differences in HA gene between goose and human H5N1 viruses. The sequence analysis of amino acid on viral protein molecules indicated that there were 7 and 9 position differences between goose and human, chicken H5N1 viruses, respectively. All the three viruses share multiple basic amino acids (R-E-R-R-R-K-K-R) at the cleavage site between HA1 and HA2 domain, that is associated with highly pathogenic H5 avian viruses. Except one more glycosylation site located at 156 position in the chicken strain, there were 7 glycosylation sites at same positions in three virus HA protein molecules. The analysis of NA protein molecule indicated that the stalk region which extends from the viral membrane up to amino acid 85, human and chicken viruses had a 19 amino-acid deletion as compared with that of goose virus, while the goose NA gene was closely related to A/Parrot/Ulster/73 (H7N1) virus. Therefore, goose H5N1 virus HA and NA genes were avian in origin and were different from those of human and chicken H5N1 viruses. In our knowledge, this is the first time that the avian H5N1 virus was found causing influenza outbreak in goose. Why was A/Goose/Guangdong/2/96(H5N1) virus virulent for geese? It might be related to the substitution of amino acid located at 138 position near by RBS on HA protein molecule and 19 amino acids insertion on NA protein molecule as compared with those of human and chicken H5N1 viruses.

            Descriptors:  influenza virology, influenza A virus avian genetics, influenza A virus human genetics, poultry diseases virology, amino acid sequence, chick embryo, geese virology, influenza veterinary, influenza A virus avian isolation and purification, influenza A virus human isolation and purification, molecular sequence data, sequence homology, amino acid.

Ha, Y., D.J. Stevens, J.J. Skehel, and D.C. Wiley (2002). H5 avian and H9 swine influenza virus haemagglutinin structures: possible origin of influenza subtypes. EMBO Journal 21(5): 865-75.  ISSN: 0261-4189.

            NAL Call Number:  QH506.E46

            Abstract:  There are 15 subtypes of influenza A virus (H1-H15), all of which are found in avian species. Three caused pandemics in the last century: H1 in 1918 (and 1977), H2 in 1957 and H3 in 1968. In 1997, an H5 avian virus and in 1999 an H9 virus caused outbreaks of respiratory disease in Hong Kong. We have determined the three-dimensional structures of the haemagglutinins (HAs) from H5 avian and H9 swine viruses closely related to the viruses isolated from humans in Hong Kong. We have compared them with known structures of the H3 HA from the virus that caused the 1968 H3 pandemic and of the HA--esterase--fusion (HEF) glycoprotein from an influenza C virus. Structure and sequence comparisons suggest that HA subtypes may have originated by diversification of properties that affected the metastability of HAs required for their membrane fusion activities in viral infection.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, influenza A virus avian chemistry, porcine chemistry, orthomyxoviridae classification, amino acid motifs, amino acid sequence, amino acid substitution,  crystallography, x-ray, evolution, molecular, hemagglutinin glycoproteins, influenza virus genetics, hemagglutinin glycoproteins, influenza virus physiology, hydrogen-ion concentration, avian classification, influenza A virus avian genetics, avian physiology, porcine classification, porcine genetics, porcine physiology, membrane fusion, models, molecular, molecular sequence data, protein conformation, protein structure, secondary, rotation, sequence alignment, sequence homology, amino acid, structure activity relationship.

Ha, Y., D.J. Stevens, J.J. Skehel, and D.C. Wiley (2001). X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proceedings of the National Academy of Sciences of the United States of America 98(20): 11181-6.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  The three-dimensional structures of avian H5 and swine H9 influenza hemagglutinins (HAs) from viruses closely related to those that caused outbreaks of human disease in Hong Kong in 1997 and 1999 were determined bound to avian and human cell receptor analogs. Emerging influenza pandemics have been accompanied by the evolution of receptor-binding specificity from the preference of avian viruses for sialic acid receptors in alpha2,3 linkage to the preference of human viruses for alpha2,6 linkages. The four new structures show that HA binding sites specific for human receptors appear to be wider than those preferring avian receptors and how avian and human receptors are distinguished by atomic contacts at the glycosidic linkage. alpha2,3-Linked sialosides bind the avian HA in a trans conformation to form an alpha2,3 linkage-specific motif, made by the glycosidic oxygen and 4-OH of the penultimate galactose, that is complementary to the hydrogen-bonding capacity of Gln-226, an avian-specific residue. alpha2,6-Linked sialosides bind in a cis conformation, exposing the glycosidic oxygen to solution and nonpolar atoms of the receptor to Leu-226, a human-specific residue. The new structures are compared with previously reported crystal structures of HA/sialoside complexes of the H3 subtype that caused the 1968 Hong Kong Influenza virus pandemic and analyzed in relation to HA sequences of all 15 subtypes and to receptor affinity data to make clearer how receptor-binding sites of HAs from avian viruses evolve as the virus adapts to humans.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian physiology, porcine physiology, receptors, virus chemistry, receptors, virus physiology, amino acid sequence, binding sites, conserved sequence, crystallography, x -ray, ducks, hydrogen bonding, models, molecular, N-acetylneuraminic acid, protein conformation, swine.

Hablolvarid, M.H., I.S. Haghdost, S.A. Pourbakhsk, and M.R. Gholami (2003). A study on histopathologic changes in chicken following intravenous inoculation with avian influenza virus A/Chicken/Iran/259/1998(H9N2). Archives of Razi Institute (55): 41-53.  ISSN: 0365-3439.

            NAL Call Number:  QR189.A73

            Descriptors:  avian influenza virus, clinical aspects, experimental infections, histopathology, poultry.

Haller, O. (1975). A mouse hepatotropic variant of influenza virus. Archives of Virology 49(2-3): 99-116.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A hepatotropic variant of avian influenza virus A/Turkey/England 63 (Hav 1, Nav 3) was selected by serial passages in mouse liver. Adaptation to this organ was established after 13 in vivo passages and was found to improve during further passages as shown by increasing rates of replication in livers of ICR mice. The mutant virus finally selected was stable and differed from the original virus mainly in lethality upon intraperitoneal injection in mice, in its ability to grow to high titers in livers of susceptible animals and in plaque morphology in chick embryo fibroblasts. No differences were detected in hemagglutination inhibition and neutralization by standard mouse antisera. Pathogenicity for the liver was independent of the route of inoculation, included other laboratory animals sensitive to influenza virus and could be inhibited by amantadine. Fatal hepatitis in 50 per cent of susceptible mice by the intraperitoneal route required from 10 to 20 EID50-. Pathological changes consisted of severe necrosis of liver parenchyma accompanied by release of F antigen into the serum and were apparently due to virus replication in hepatic cells as evidenced by immunofluorescence. The main implications of this animal model for studies on experimental hepatitis and on myxovirus-host interactions in an organ not usually associated with influenza are discussed.

            Descriptors:  adaptation, physiological, hepatitis A microbiology, liver microbiology, mutation, orthomyxoviridae growth and development, amantadine therapeutic use, antigens, viral, disease models, animal, guinea pigs, hamsters, hepatitis A pathology, hepatitis A prevention and control, liver immunology, liver pathology, mice, mice inbred strains, orthomyxoviridae immunology, orthomyxoviridae pathogenicity, rats, virus replication.

Haller, O., H. Arnheiter, and J. Lindenmann (1976). Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression. Infection and Immunity 13(3): 844-54.  ISSN: 0019-9567.

            NAL Call Number:  QR1.I57

            Abstract:  Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver.

            Descriptors:  immunosuppression, influenza prevention and control, liver microbiology, orthomyxoviridae pathogenicity, antigens viral analysis,  cyclophosphamide pharmacology, hepatectomy, influenza genetics, liver pathology, liver regeneration, methotrexate pharmacology, mice, mice inbred A, mice inbred c57bl, mice inbred ICR, orthomyxoviridae growth and development, procarbazine pharmacology, reticuloendothelial system microbiology, silicon dioxide pharmacology, thorium dioxide pharmacology.

Haller, O., H. Arnheiter, and J. Lindenmann (1979). Natural, genetically determined resistance toward influenza virus in hemopoietic mouse chimeras. Role of mononuclear phagocytes. Journal of Experimental Medicine 150(1): 117-26.  ISSN: 0022-1007.

            NAL Call Number:  448.8 J822

            Abstract:  Radiation chimeras produced by crosswise transfers of bone-marrow cell among histocompatible mice susceptible, or genetically resistant, to lethal challenge by a number of myxoviruses were used to test whether macrophage resistance (as assessed in vitro) and resistance of the animal (as measured in vivo), both previously shown to be brought about by the gene Mx, were causally related. 49 chimeras were tested individually, both of resistance of their macrophages to in vitro challenge with M-TUR (a strain of avian influenza virus A/Turkey/England/63 adapted to grow in cultured mouse peritoneal macrophages), and for resistance of the animal in vivo upon challenge with pneumotropic, neurotropic, or hepatotropic influenza viruses. Cultivated Kupffer cells and peritoneal macrophages harvested from chimeric mice expressed the resistance phenotype of the bone-marrow donor irrespective of the host environment in which they had differentiated. However, susceptibility or resistance in vivo was according to the genotype of the host. Thus, inborn resistance of radiation chimeras was found to be independent of Mx-gene expression in cells of the hemopoietic system.

            Descriptors:  hematopoietic stem cells immunology, immunity, natural, orthomyxoviridae immunology, phagocytes immunology, radiation chimera, genotype, hematopoietic stem cell transplantation, influenza immunology, mice, mice inbred strains genetics, homologous transplantation.

Hamzehei, M. and N. Ledinko (1980). Inhibition of influenza A virus replication by rifampicin and selenocystamine. Journal of Medical Virology 6(2): 169-74.  ISSN: 0146-6615.

            Abstract:  The effects of selenocystamine, an inhibitor of influenza virus RNA-dependent RNA polymerase in vitro activity, in the antibiotic rifampicin were studied on influenza A/PR/8/34 (HON1) infection in embryonated eggs. Both drugs completely inhibited hemagglutinating and infective virus yields when added at relatively early times postinfection. Maximal inhibition was produced by apparently noncytotoxic concentrations of 50 microgram of selenocystamine, or of 400 microgram of rifampicin, per egg.

            Descriptors:  cystamine analogs and derivatives, influenza A virus avian drug effects, organoselenium compounds, rifampin pharmacology, selenium pharmacology, virus replication drug effects, chick embryo, cystamine administration and dosage, cystamine pharmacology, avian growth and development, rifampin administration and dosage, selenium administration and dosage, time factors, tissue culture.

Hannoun, C. (1977). Isolation from birds of influenza viruses with human neuraminidase. Developments in Biological Standardization 39: 469-72.  ISSN: 0301-5149.

            NAL Call Number:  QR180.3.D4

            Abstract:  Attempts at virus isolation from cloacal swabs resulted in the recovery of 10 strains of hemagglutinating viruses from a total of 349 ducks, mainly shelducks (Tadorna tadorna) captured in the north of France. Four of these isolates were identified as influenza strains corresponding to the following antigenic composition: Hav6-N2, Hav6-Nav4 and Hav1-N2 (2 strains). Shelduck is known to be a partially migratory species, wintering in western Europe, some of them migrating northward to Scandinavia during the summer. The captures were made between November 1976 and February 1977: one of the birds was caught four times and was found to be negative for virus in November, positive in December (isolation of a strain Hav6-Nav4), negative again in January and February. Blood taken in February did not show the presence of HI antibodies to the homologous virus.

            Descriptors:  antigens, viral, ducks microbiology, influenza A virus avian isolation and purification, neuraminidase immunology, antibodies, viral, cloaca microbiology, France, hemagglutination inhibition tests, hemagglutinins viral, avian enzymology, avian immunology, human enzymology, seasons.

Harboe, A., R. Schoyen, and A. Bye Hansen (1966). Haemagglutination inhibition by antibody to host material of fowl plague virus grown in different tissues of chick chorioallantoic membranes. Acta Pathologica Et Microbiologica Scandinavica 67(4): 573-8.  ISSN: 0365-5555.

            Descriptors:  endoderm, fetal membranes, hemagglutination inhibition tests, influenza A virus avian immunology, antibodies, chick embryo, glycosaminoglycans, hemagglutination tests, orthomyxoviridae immunology, virus cultivation.

Harley, V.R., P.J. Hudson, B.E. Coupar, P.W. Selleck, H. Westbury, and D.B. Boyle (1990). Vaccinia virus expression and sequence of an avian influenza nucleoprotein gene: potential use in diagnosis. Archives of Virology 113(1-2): 133-41.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The nucleoprotein (NP) gene from avian influenza strain A/Shearwater/Aust/1/72 (H6N5) was cloned, sequenced, and expressed in vaccinia virus for the production of potent sera in immunised rabbits. The NP gene is 1565 bp and shares greater than 95% amino acid sequence identity with other NPs of the avian subtype. The recombinant NP expressed by vaccinia virus comigrated with endogenous A/Shearwater/Aust/1/72 NP by Western blot analysis. Polyclonal rabbit sera raised against recombinant NP was evaluated in an antigen capture ELISA system as a potential diagnostic tool for the detection of avian influenza. All type A strains, comprising several HA and NA subtypes, but not type B nor other avian viruses, were detected.

            Descriptors:  fowl plague diagnosis, genes viral, influenza A virus avian genetics, nucleoproteins genetics, vaccinia virus genetics, viral core proteins, viral proteins genetics, amino acid sequence, antibodies, viral immunology, base sequence, blotting, southern, cloning, molecular, DNA, viral, enzyme linked immunosorbent assay, avian immunology, molecular sequence data, nucleoproteins immunology, predictive value of tests, thymidine kinase genetics, vaccinia virus immunology, viral proteins immunology.

Harley, V.R., K.A. Mather, B.E. Power, J.L. McKimm Breschkin, and P.J. Hudson (1990). Characterisation of an avian influenza virus nucleoprotein expressed in E. coli and in insect cells. Archives of Virology 113(3/4): 267-277.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The nucleoprotein (NP) gene from influenza virus A/Shearwater/Australia/72 has been expressed intracellularly in both E. coli and insect cells. E. coli-derived NP was identified by Western blot analysis as a 56 kDa protein which co-migrates with virion-derived NP. This protein was purified by immunoaffinity chromatography and a nitrocellulose binding assay showed that NP formed complexes with positive- and negative-sense influenza neuraminidase RNA transcribed in vitro. ELISA and Western blot analysis revealed that recombinant NP of 56 kDa was produced in high yields in insect cells using a baculovirus vector. Immunofluorescence microscopy revealed that NP was localised to the nucleus of infected insect cells.

            Descriptors:  avian influenza virus, viral proteins, nucleoproteins, RNA, recombination, purification, characterization, Escherichia coli, Autographa californica, nuclear polyhedrosis viruses.

Harley, V.R., C.W. Ward, and P.J. Hudson (1989). Molecular cloning and analysis of the N5 neuraminidase subtype from an avian influenza virus. Virology 169(1): 239-43.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The neuraminidase (NA) gene from the prototype N5 influenza virus, A/Shearwater/Australia/72, has been cloned and completely sequenced. An open reading frame of 1404 bp (468 amino acids) is flanked by 20-bp 5'- and 31-bp 3'-untranslated regions. The deduced amino acid sequence of the N5 gene was compared with sequences from N2, N1, N7, N8, and N9 subtypes. One hundred thirteen amino acid residues (24%) are completely conserved across subtypes and include active site residues, cysteines, potential glycosylation sites, and certain glycines which suggests that these subtypes share a common ancestor and adopt the same 3-D conformation. Three groups can be assigned from amino acid homologies: (i) N5, N8, N1; (ii) N7, N9; and (iii) N2 where the percentage identity within groups is 55-68% and between groups is 40-46%, the N5-N8 pair bearing the closest identity (68%). Phylogenetic analysis suggests that these groups diverged concurrently.

            Descriptors:  DNA, viral genetics, influenza A virus avian genetics, neuraminidase genetics, amino acid sequence, base sequence, cloning, molecular, DNA probes, deoxyribonuclease ecori,  avian enzymology, molecular sequence data, phylogeny.

Harms, E., W. Rohde, F. Bosch, and C. Scholtissek (1978). Biochemical studies on influenza viruses. II. Assignment of gene functions to RNA segments 5, 7, and 8 of fowl plague virus and virus N. Virology 86(2): 413-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian analysis, influenza A virus analysis, RNA viral analysis, genes viral, avian genetics, influenza A virus genetics, nucleic acid hybridization, peptides analysis, recombination, genetic, viral proteins analysis.

Harms, E., W. Rohde, and C. Scholtissek (1978). Minor nucleic acids in influenza virus. Journal of General Virology 40(3): 691-4.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  A nucleic acid fraction consisting of RNA and DNA sequences with an apparent mol. wt. of 1.4 to 1.5 x 10(6) is present in minor amounts in purified influenza virus. The RNA is virus-specific and in the case of fowl plague virus (FPV) contains sequences of genes 2 and 7 which code for one of the proteins constituting the polymerase complex and for the matrix protein respectively.

            Descriptors:  DNA analysis, influenza A virus avian analysis, RNA viral analysis, genes viral, avian genetics, molecular weight, nucleic acid hybridization, viral genetics, viral proteins biosynthesis.

Harvey, R., A.C. Martin, M. Zambon, and W.S. Barclay (2004). Restrictions to the adaptation of influenza a virus H5 hemagglutinin to the human host. Journal of Virology 78(1): 502-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The binding specificities of a panel of avian influenza virus subtype H5 hemagglutinin (HA) proteins bearing mutations at key residues in the receptor binding site were investigated. The results demonstrate that two simultaneous mutations in the receptor binding site resulted in H5 HA binding in a pattern similar to that shown by human viruses. Coexpression of the ion channel protein, M2, from most avian and human strains tested protected H5 HA conformation during trafficking, indicating that no genetic barrier to the reassortment of the H5 surface antigen gene with internal genes of human viruses existed at this level.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza A virus, avian pathogenicity, avian classification, influenza A virus, avian genetics, receptors, cell surface metabolism, adaptation, physiological genetics, binding sites genetics, erythrocytes metabolism, hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus metabolism, models, molecular, point mutation, species specificity.

Hastie, N.D. and B.W. Mahy (1973). RNA-dependent RNA polymerase in nuclei of cells infected with influenza virus. Journal of Virology 12(5): 951-61.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  cell nucleus enzymology, DNA directed RNA polymerases metabolism, orthomyxoviridae enzymology, RNA metabolism, cell fractionation,  centrifugation, density gradient, chick embryo, cytochrome reductases analysis, cytochrome C group, DNA, viral isolation and purification, dactinomycin pharmacology, enzyme induction, fibroblasts, hemagglutination tests, influenza A virus avian enzymology, magnesium pharmacology, manganese pharmacology, microsomes enzymology, NAD, nucleic acid hybridization, proteins metabolism, sucrose, time factors, tritium.

Hatta, M., P. Gao, P. Halfmann, and Y. Kawaoka (2001). Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293(5536): 1840-2.  ISSN: 0036-8075.

            NAL Call Number:  470 Sci2

            Abstract:  In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.

            Descriptors:  influenza epidemiology, influenza virology, influenza A virus genetics, influenza A virus pathogenicity, amino acid sequence, birds virology, DNA, recombinant genetics, hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus genetics, hemagglutinin glycoproteins, influenza virus metabolism, Hong Kong epidemiology, influenza mortality, influenza transmission , influenza A virus avian genetics, avian pathogenicity, avian physiology, human genetics, human pathogenicity, human physiology, influenza A virus physiology, lung virology, mice, mutation, missense genetics, reassortant viruses genetics, reassortant viruses pathogenicity, reassortant viruses physiology, viral proteins chemistry, viral proteins genetics, viral proteins metabolism.

Hatziioannou, T., E. Delahaye, F. Martin, S.J. Russell, and F.L. Cosset (1999). Retroviral display of functional binding domains fused to the amino terminus of influenza hemagglutinin. Human Gene Therapy 10(9): 1533-44.  ISSN: 1043-0342.

            Abstract:  We have previously shown that retroviral vector particles derived from Moloney murine leukemia virus (Mo-MuLV) can efficiently incorporate influenza hemagglutinin (HA) glycoproteins from fowl plague virus (FPV), thus conferring a broad tropism to the vectors. To modify its host range, we have engineered the FPV HA to display four different polypeptides on its N terminus: the epidermal growth factor, an anti-human MHC class I molecules scFv (single-chain antibody), an anti-melanoma antigen scFv, and an IgG Fc-binding polypeptide. All recombinant HA glycoproteins were correctly expressed and processed, and efficiently incorporated into Mo-MuLV retroviral particles, indicating that amino-terminal insertion of large polypeptides did not alter the conformation of HA chimeras. Virions carrying the different chimeras bound specifically to cells expressing the targeted cell surface molecules of each ligand. In addition, all virion types were infectious but exhibited various degrees of specificity regarding the use of the targeted cell surface molecule versus the wild-type FPV HA receptor for cell entry and infection. For some ligands tested, infectivity was significantly increased on cells that express the targeted receptor, compared with cells that express only the wild-type HA receptor. Furthermore, some polypeptides could abolish infectivity via the wild-type FPV HA receptor. Our data therefore indicate that it is possible to engineer the HA envelope glycoprotein by fusing ligands to its amino-terminal end without affecting its fusion activity.

            Descriptors:  genetic vectors, hemagglutinin glycoproteins, influenza virus genetics, moloney murine leukemia virus, peptides genetics, 3T3 cells, antibodies, neoplasm genetics, binding sites, epidermal growth factor genetics, gene fusion, hemagglutinin glycoproteins, influenza virus metabolism, immunoglobulin fragments genetics, immunoglobulin variable region genetics, influenza A virus avian genetics, mice, peptides metabolism, recombinant fusion proteins genetics, tumor cultured cells, virion metabolism.

Hatziioannou, T., S. Valsesia Wittmann, S.J. Russell, and F.L. Cosset (1998). Incorporation of fowl plague virus hemagglutinin into murine leukemia virus particles and analysis of the infectivity of the pseudotyped retroviruses. Journal of Virology 72(6): 5313-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  We describe retrovirus particles carrying the fowl plague virus (FPV) hemagglutinin (HA). When expressed in cells providing Moloney murine leukemia virus (MoMLV) Gag and Pol proteins and a lacZ retroviral vector, FPV HA was found to be efficiently expressed, correctly processed, and stably incorporated into retroviral particles. HA-bearing retroviruses were infectious with a wide host range and were only 10-fold less infectious than retroviruses carrying wild-type MLV retroviral envelopes. We also coexpressed HA proteins in retroviral particles with chimeric MoMLV-derived envelope glycoproteins that efficiently retarget virus attachment but are only weakly fusogenic. Our results suggest that HA can in some cases enhance the fusion ability of these retroviral particles, depending on the cell surface molecule that is used as a receptor.

            Descriptors:  hemagglutinins genetics, influenza A virus avian genetics, leukemia virus, murine genetics, viral fusion proteins genetics, gene products, gag genetics, gene products, pol genetics, lac operon, mice, recombination, genetic, virion genetics.

Hausmann, J., E. Kretzschmar, W. Garten, and H.D. Klenk (1997). Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides. Journal of General Virology 78(Pt. 12): 3233-45.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Intracellular transport, glycosylation, tetramerization and enzymatic activity of the neuraminidase (NA) of fowl plague virus (FPV) were analysed in vertebrate cells after expression from a vaccinia virus vector. Tetramerization occurred with a half-time of 15 min, whereas passage through the medial Golgi apparatus and transport to the plasma membrane occurred with half-times of 2 and 3 h, respectively, suggesting a step in NA maturation beyond tetramerization that limits the rate of transport to the medial Golgi. NA transport rates were about fourfold slower than those of haemagglutinin (HA). Slow transport and processing of FPV NA was not altered by coexpression of FPV HA, nor was the transport rate of HA influenced by NA. The slow transport kinetics of NA were also observed in FPV-infected CV-1 cells. As deduced from the coding sequence, FPV NA has the shortest stalk of all naturally occurring NAs described to date and contains only three potential N-glycosylation sites, which are all located in the globular head domain. Elimination of each of the three N-glycosylation sites revealed that the two oligosaccharides at positions 124 and 66 are of the complex type, whereas the one at Asn-213 remains in mannose-rich form. The glycosylation mutants showed also that oligosaccharides at positions 124 and 213 of FPV NA modulate enzymatic activity. Transport of NA is not influenced by single elimination of any of the three oligosaccharide attachment sites. Mutational analysis of the three Cys residues not involved in intrachain disulfide pairing revealed that Cys-49 in the stalk of the NA molecule is responsible for the formation of disulfide-linked dimers. Analysis of cysteine mutants of FPV NA also demonstrated that disulfide-linked dimers are not absolutely necessary for the formation of enzymatically active tetramers but may stabilize the quaternary structure of NA.

            Descriptors:  birds virology, influenza A virus avian enzymology, neuraminidase metabolism, biological transport, cysteine, enzyme activation, glycosylation, oligosaccharides.

Hay, A.J. (1974). Studies on the formation of the influenza virus envelope. Virology 60(2): 398-418.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  hemagglutinins viral, orthomyxoviridae growth and development, virus replication, autoradiography, cell membrane analysis, cell membrane enzymology, chick embryo, chromatography, affinity, dihydrolipoamide dehydrogenase analysis, electrophoresis, polyacrylamide gel, endoplasmic reticulum analysis, fibroblasts, glycopeptides analysis, glycoproteins analysis, influenza A virus avian growth and development, influenza A virus avian immunology, methionine, microscopy, electron, neuraminic acids analysis, nucleotidases analysis, orthomyxoviridae immunology, peptides analysis, sulfur radioisotopes.

Hay, A.J., B. Lomniczi, A.R. Bellamy, and J.J. Skehel (1977). Transcription of the influenza virus genome. Virology 83(2): 337-55.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, influenza A virus avian genetics, RNA, messenger biosynthesis, viral biosynthesis, transcription, genetic, cell line, avian metabolism, poly A, viral analysis, virion metabolism.

Hay, A.J. and J.J. Skehel (1979). Characterization of influenza virus RNA transcripts synthesized in vitro. Journal of General Virology 44(3): 599-608.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Polyadenylated transcripts synthesized in vitro by detergent-disrupted influenza virus resemble virus mRNAs in that they possess the complement of the 3' terminus of the genome RNAs but lack sequences corresponding to the same 5' terminal region, including the homologous sequence of nucleotides 1 to 22. Transcription is initiated at the 3' terminus by both ApG and GpG as well as in the absence of added primer.

            Descriptors:  influenza A virus avian analysis, orthomyxoviridae analysis, RNA viral analysis, transcription, genetic, base sequence, cell free system, avian metabolism, nucleic acid hybridization, nucleotides analysis, poly A analysis, viral biosynthesis.

Hay, A.J., J.J. Skehel, and J. McCauley (1982). Characterization of influenza virus RNA complete transcripts. Virology 116(2): 517-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian genetics, RNA viral analysis, adenosine metabolism, base sequence, chromatography, DEAE-cellulose, chromatography, thin layer, phosphorylation, ribonucleases pharmacology, ribonucleotides analysis, transcription, genetic.

Hay, A.J., A.J. Wolstenholme, J.J. Skehel, and M.H. Smith (1985). The molecular basis of the specific anti-influenza action of amantadine. EMBO Journal 4(11): 3021-4.  ISSN: 0261-4189.

            NAL Call Number:  QH506.E46

            Abstract:  Amantadine (1-aminoadamantane hydrochloride) is effective in the prophylaxis and treatment of influenza A infections. In tissue culture this selective, strain-specific antiviral activity occurs at relatively low concentrations (5 microM or less), which inhibit either the initiation of infection or virus assembly. The data reported here demonstrate that the basis of these actions is similar and resides in the virus-coded M2 membrane protein, the product of a spliced transcript of RNA segment 7. Mutations which confer resistance to amantadine are restricted to four amino acids within a hydrophobic sequence, indicating that the drug is targetted against the putative membrane-associated portion of the molecule. The influence of the virus haemagglutinin on the amantadine sensitivity of virus strains implies that the drug may interfere with interactions between these two virus proteins.

            Descriptors:  amantadine pharmacology, influenza A virus avian drug effects, human drug effects, membrane proteins genetics, chick embryo, chickens, drug resistance, microbial, fibroblasts cytology, avian genetics, human genetics, mutation, RNA splicing, species specificity, transcription, genetic drug effects.

Hayman, M.J., J.J. Skehel, and M.J. Crumpton (1973). Purification of virus glycoproteins by affinity chromatography using Lens culinaris phytohaemagglutinin. FEBS Letters 29(2): 185-8.  ISSN: 0014-5793.

            NAL Call Number:  QD415.F4

            Descriptors:  glycoproteins isolation and purification, mammary tumor virus, mouse analysis, orthomyxoviridae analysis, parainfluenza virus 1, human analysis, viral proteins isolation and purification, chromatography, affinity, electrophoresis, polyacrylamide gel, influenza A virus avian analysis, lectins,  polysaccharides, sodium dodecyl sulfate.

He Houjun and Dai Yimi (Apr 2004)). Progress in molecular biology of avian influenza virus. Journal of Jiangxi Agricultural University (China) [Jiangxi Nongye Daxue Xuebao (China)]  26(2): 289-293.  ISSN: 1000-2286.

            Descriptors:  avian influenza virus A, molecular biology, progress.

Heller, E. and C. Scholtissek (1980). Evidence for intracistronic complementation of the product of the influenza virus gene Ptra (P3 of fowl plague virus). Journal of General Virology 49(1): 133-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The ts lesion of the fowl plague virus (FPV) mutants ts 18 and ts 236 has been located in RNA segment 2 (Ptra gene, corresponding to P3). After double-infection with these mutants and ts 90 or ts 93, which also carry a ts lesion in segment 2, plaques were formed at the non-permissive temperature (40 degrees C). These plaques cannot be passaged at 40 degrees C and exhibit a morphology which differs from those formed by the wild-type virus. The yield of infectious particles after double-infection shows a non-linear correlation between the plaque number and dilution, indicating that at least two particles are needed for infection of a cell. All experimental evidence points to an intracistronic complementation within the P3 protein.

            Descriptors:  genes, structural, genes viral, influenza A virus avian genetics, recombination, genetic, cultured cells, chick embryo, genetic complementation test, avian growth and development, mutation, plaque assay, temperature.

Henkel, J.R., G.A. Gibson, P.A. Poland, M.A. Ellis, R.P. Hughey, and O.A. Weisz (2000). Influenza M2 proton channel activity selectively inhibits trans-Golgi network release of apical membrane and secreted proteins in polarized Madin-Darby canine kidney cells. Journal of Cell Biology 148(3): 495-504.  ISSN: 0021-9525.

            NAL Call Number:  442.8 J828

            Abstract:  The function of acidification in protein sorting along the biosynthetic pathway has been difficult to elucidate, in part because reagents used to alter organelle pH affect all acidified compartments and are poorly reversible. We have used a novel approach to examine the role of acidification in protein sorting in polarized Madin-Darby canine kidney (MDCK) cells. We expressed the influenza virus M2 protein, an acid-activated ion channel that equilibrates lumenal and cytosolic pH, in polarized MDCK cells and examined the consequences on the targeting and delivery of apical and basolateral proteins. M2 activity affects the pH of only a subset of acidified organelles, and its activity can be rapidly reversed using ion channel blockers (Henkel, J.R., G. Apodaca, Y. Altschuler, S. Hardy, and O.A. Weisz. 1998. Mol. Biol. Cell. 8:2477-2490; Henkel, J.R., J.L. Popovich, G.A. Gibson, S.C. Watkins, and O.A. Weisz. 1999. J. Biol. Chem. 274:9854-9860). M2 expression significantly decreased the kinetics of cell surface delivery of the apical membrane protein influenza hemagglutinin, but not of the basolaterally delivered polymeric immunoglobulin receptor. Similarly, the kinetics of apical secretion of a soluble form of gamma-glutamyltranspeptidase were reduced with no effect on the basolaterally secreted fraction. Interestingly, M2 activity had no effect on the rate of secretion of a nonglycosylated protein (human growth hormone [hGH]) that was secreted equally from both surfaces. However, M2 slowed apical secretion of a glycosylated mutant of hGH that was secreted predominantly apically. Our results suggest a role for acidic trans-Golgi network pH in signal-mediated loading of apical cargo into forming vesicles.

            Descriptors:  Golgi apparatus metabolism, influenza A virus avian metabolism, ion channels metabolism, viral matrix proteins metabolism, cell line, cell membrane metabolism, cell polarity, dogs, gene expression, hemagglutinin glycoproteins, influenza virus biosynthesis, hemagglutinin glycoproteins, influenza virus genetics, protons, receptors, polymeric immunoglobulin biosynthesis, receptors, polymeric immunoglobulin genetics, viral matrix proteins genetics.

Henkel, J.R. and O.A. Weisz (1998). Influenza virus M2 protein slows traffic along the secretory pathway. pH perturbation of acidified compartments affects early Golgi transport steps.  Journal of Biological Chemistry 273(11): 6518-24.  ISSN: 0021-9258.

            NAL Call Number:  381 J824

            Abstract:  M2, an acid-activated ion channel, is an influenza A virus membrane protein required for efficient nucleocapsid release after viral fusion with the endosomal membrane. Recombinant M2 slows protein traffic through the Golgi complex (Sakaguchi, T., Leser, G. P)., and Lamb, R. A. (1996) J. Cell Biol. 133, 733-47). Despite its critical role in viral infection, little is known about the subcellular distribution of M2 or its fate following delivery to the plasma membrane (PM). We measured the kinetics of M2 transport in HeLa cells, and found that active M2 reached the PM considerably more slowly than inactive M2. In addition, M2 delayed intra-Golgi transport and cell surface delivery of influenza hemagglutinin (HA). We hypothesized that the effects of M2 on transport through non-acidified compartments are due to inefficient retrieval from the trans-Golgi of machinery required for intra-Golgi transport. In support of this, acutely activated M2 had no effect on intra-Golgi transport of HA, but still slowed HA delivery to the PM. Thus, M2 has an indirect effect on early transport steps, but a direct effect on late steps in PM delivery. These findings may help explain the conflicting and unexplained effects on protein traffic observed with other perturbants of intraorganelle pH such as weak bases and inhibitors of V-type ATPases.

            Descriptors:  Golgi apparatus metabolism, influenza A virus avian metabolism, ion channels secretion, viral matrix proteins secretion, amantadine pharmacology, antiviral agents pharmacology, biological transport drug effects, cell compartmentation, cell membrane metabolism, HeLa cells, hemagglutinin glycoproteins, influenza virus metabolism, hydrogen-ion concentration, imidazoles pharmacology, spiro compounds pharmacology.

Herget, M. and C. Scholtissek (1993). A temperature-sensitive mutation in the acidic polymerase gene of an influenza A virus alters the regulation of viral protein synthesis. Journal of General Virology 74(Pt. 9): 1789-94.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The temperature-sensitive defect of mutant ts 263 of fowl plague virus (FPV) is located in the acidic polymerase (PA) gene and is due to a single base substitution (C2036T), which leads to an amino acid replacement (Ala671 to Val) in a highly conserved region of the protein. During passage at 33 degrees C ts 263 stably carries over a ninth RNA segment, which consists of a truncated PA gene. Although the deletion is in-frame and it is transcribed into mRNA, no corresponding protein is detected in vivo. After reversion to wild-type this extra RNA segment is immediately lost. At the non-permissive temperature of 40 degrees C no significant viral products of ts 263 are synthesized. Under semi-permissive conditions there is a relative, but very significant over-production of the M1 protein, which is not accompanied by a corresponding elevated M1 mRNA synthesis. These results are in agreement with the idea that the PA protein is involved in the regulation of viral protein synthesis at the level of expression of mRNA. Preinfection of chicken embryo cells with ts 263 at a semi-permissive temperature interferes with the replication of FPV wild-type indicating that premature availability of M1 might be detrimental for influenza virus replication.

            Descriptors:  DNA directed RNA polymerases genetics, gene expression regulation, viral, genes viral, influenza A virus avian genetics, avian metabolism, mutation, viral proteins biosynthesis, amino acid sequence, blotting, northern, cultured cells, chick embryo, cloning, molecular, conserved sequence, crosses, genetic, DNA directed RNA polymerases metabolism, avian physiology, polymerase chain reaction, RNA, messenger biosynthesis,  messenger metabolism, viral isolation and purification, viral metabolism, temperature, virus replication.

Hernandez Magdaleno, A., M.T. Casaubon Hugening, and J. Garcia Garcia. (1998). Viremia durante la infeccion del virus de influenza aviar (h5n2) altamente patogeno en aves susceptibles y en aves inmunizadas. [Study of the viremia during the infecction of a highly pathogenic avian influenza virus (h5n2) on susceptible and immunized chickens]. In: 34 Reunion Nacional de Investigacion Pecuaria, Queretaro, Qro. (Mexico),    p. 250.

            Abstract: El objetivo de la presente investigacion fue contribuir al estudio de la patogenia del virus de influenza aviar (H5N2) altamente patogeno, en aves susceptibles (Av-Susc) y en aves inmunizadas (Av-Inm), durante las primeras 72 horas post-inoculacion (hpi), a traves del estudio de la viremia. Se formaron dos grupos de 100 aves libres de patogenos especificos. A los 8 dias de edad, uno de los grupos fue inmunizado con una vacuna emulsionada contra influenza aviar (IA) y el otro grupo permanecio sin inmunizar. A las cuatro semanas de edad, ambos grupos de aves fueron inoculados via intranasal con 1 x 103 DLEP50 del virus A/Chicken/Queretaro/14588-19/95 (H5N2), altamente patogeno. Se tomaron aleatoriamente 3 aves de cada grupo a las 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 y 72 hpi. De cada ave se tomo una muestra de sangre directamente del corazon para aislamiento y titulacion viral. A partir de las muestras de sangre se pudo identificar y cuantificar el virus de influenza aviar de alta patogenicidad, solo en las Av-Susc. El aislamiento e identificacion del virus se realizo a partir de las 28 hpi en el 100% de las Av-Susc. El titulo del virus circulante en las Av-Susc a las 28 hpi fue de 106.12 DLEP50/ml de sangre; posteriormente el titulo de virus circulante se mantuvo en un rango de 105.69 a 108.06 DLEP50/ml, entre las 32 y 68 hpi. La mayor cantidad de virus circulante, fue detectado a las 72 hpi, con un titulo de 109.04 DLEP50/ml de sangre. La conversion del titulo viral a numeros naturales, indica que entre las 28 y 68 hpi, las Av-Susc, tuvieron menos de 200,000,000 DLEP50/ml de sangre. A las 72 hpi, el titulo de virus circulante fue de 109.04 DLEP50/ml de sangre, lo que al convertirse a numeros naturales equivale a 1,096,478,196 DLE50/ml de sangre, siendo este el valor maximo que se identifico. La titulacion del virus circulante en sangre, sugiere que el virus tuvo varios ciclos de replicacion local, antes de diseminarse. La replicacion viral fue muy eficiente, si se toma en cuenta que la dosis inoculada contenia 1,000 DLEP50 de virus y a las 72 hpi, la cantidad de virus circulante fue de 1,096,478,196 DLEP50/ml de sangre. Las Av-Inm no presentaron viremia, lo que sugiere que uno de los mecanismos por el cual la vacunacion previene la mortalidad es que evita la viremia.

            Descriptors: broiler chickens, avian influenza virus, pathogenicity, immunity, Septicaemia, bacterioses, biological properties, birds, chickens, domestic animals, Galliformes, infectious diseases, influenza virus, livestock, meat animals, microbial properties, orthomyxoviridae, poultry, useful animals, viruses.

Hess, W.R. and A.H. Dardiri (1968). Some properties of the virus od duck plague. Archiv Fur Die Gesamte Virusforschung 24(1): 148-53.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  ducks, influenza A virus avian drug effects, acridines, biometry, chick embryo, chloroform pharmacology, enzymes pharmacology, ethyl ethers pharmacology, filtration, heat, hydrogen-ion concentration, staining and labeling.

Hietanen, T.E. and K.S. Wise (1976). Avian influenza virus adapted to grow in L1210 mouse leukemia in vitro. Archives of Virology 51(3): 243-9.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Descriptors:  influenza A virus avian growth and development, adaptation, biological, cell line, leukemia L1210, mice, virus cultivation, virus replication.

Higgins, D.A., K.F. Shortridge, and P.L. Ng (1987). Bile immunoglobulin of the duck (Anas platyrhynchos). II. Antibody response in influenza A virus infections. Immunology 62(3): 499-504.  ISSN: 0019-2805.

            NAL Call Number:  448.3 Im6

            Abstract:  The capacity of the IgM-like bile immunoglobulin (IgX) of the duck (Anas platyrhynchos) to express antibody activity to H3N2 influenza A viruses, and the dependence of this activity on the co-existence of serum IgM antibodies were investigated. Ducklings infected orally and intranasally at 15-29 days of age with viruses isolated from different host species were examined for haemagglutination-inhibiting (HI) antibodies in biles and sera 16-29 days after infection (p.i.). All biles had antibodies associated with IgX; all sera had antibodies associated only with the 7.8S IgG. Following oral infection of birds 42-days-old with influenza A/duck/HK/7/75 virus, serum HI antibodies were an initial IgM response occurring from 5-12 days p.i., followed by the appearance of 7.8S IgG antibodies. Virus-neutralizing (VN) antibodies in serum were also biphasic; isotype classification was not attempted. Bile IgX developed HI and VN activity. HI antibodies reached peak titres 12 days p.i. and fell to low levels by 24 days p.i. VN antibodies also reached peak titres 12 days p.i., but thereafter persisted at quite high levels throughout the experiment. Development of high titres of antibody in bile coincided with the termination of virus excretion in faeces. These experiments confirm that bile IgX of the duck can function as antibody in response to influenza A viruses, and that its activity appears to be independent of serum IgM. Its possible relevance in determining survival of virus in the intestine is discussed.

            Descriptors:  antibodies, viral analysis, bile immunology, fowl plague immunology, immunoglobulins analysis, influenza A virus avian immunology, ducks, hemagglutination inhibition tests, immunoglobulin G analysis, immunoglobulin M analysis.

Hinshaw, V.S., D.J. Alexander, M. Aymard, P.A. Bachmann, B.C. Easterday, C. Hannoun, H. Kida, M. Lipkind, J.S. MacKenzie, K. Nerome, and et al. (1984). Antigenic comparisons of swine-influenza-like H1N1 isolates from pigs, birds and humans: an international collaborative study. Bulletin of the World Health Organization 62(6):  871-8.  ISSN: 0042-9686.

            NAL Call Number:  449.9 W892B

            Descriptors:  antigens, viral analysis, influenza A virus, porcine immunology, influenza A virus immunology, antibodies, monoclonal immunology, hemagglutination inhibition tests, hemagglutination tests, immune sera, avian immunology, influenza A virus human immunology, porcine isolation and purification.

Hinshaw, V.S., W.J. Bean, R.G. Webster, and G. Sriram (1980). Genetic reassortment of influenza A viruses in the intestinal tract of ducks. Virology 102(2): 412-419.

            NAL Call Number:  448.8 V81

            Descriptors:  avian influenza virus, surveys, genetic reassortment, ducks.

Hinshaw, V.S., C.W. Olsen, N. Dybdahl Sissoko, and D. Evans (1994). Apoptosis: a mechanism of cell killing by influenza A and B viruses. Journal of Virology 68(6): 3667-3673.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In previous studies, we observed that the virulent avian influenza A virus A/Turkey/Ontario/7732/66 (Ty/Ont) induced severe lymphoid depletion in vivo and rapidly killed an avian lymphocyte cell line (RP9) in vitro. In examining the mechanism of cell killing by this virus, we found that Ty/Ont induced fragmentation of the RP9 cellular DNA into a 200-bp ladder and caused ultrastructural changes characteristic of apoptotic cell death by 5 h after infection. We next determined that the ability to induce apoptosis was not unique to Ty/Ont. In fact, a variety of influenza A viruses (avian, equine, swine, and human), as well as human influenza B viruses, induced DNA fragmentation in a permissive mammalian cell line, Madin-Darby canine kidney (MDCK), and this correlated with the development of cytopathic effect during viral infection. Since the proto-oncogene bcl-2 is a known inhibitor of apoptosis, we transfected MDCK cells with the human bcl-2 gene; these stably transfected cells (MDCKbcl-2) did not undergo DNA fragmentation after virus infection. In addition, cytotoxicity assays at 48 to 72 h after virus infection showed a high level of cell viability for MDCKbcl-2 compared with a markedly lower level of viability for MDCK cells. These studies indicate that influenza A and B viruses induce apoptosis in cell cultures: thus, apoptosis may represent a general mechanism of cell death in hosts infected with influenza viruses.

            Descriptors:  dogs, avian influenza virus, equine influenza virus, swine influenza virus, pathogenicity, DNA, pathogenesis, kidneys, cell culture, genes, mankind, toxicity, acids, animal morphology, biological properties, canidae, Carnivora, cell structure, chromosomes, culture techniques, in vitro culture, influenza virus, mammals, microbial properties, nucleic acids, nucleic compounds, nucleus, organic acids, urinary tract, urogenital system, viruses, cell death, DNA fragmentation, bcl-2 gene, cytopathogenicity, DNA modification, infections, cell lines, transfection, man, cytotoxicity.

Hinshaw, V.S., R.G. Webster, and R.J. Rodriguez (1981). Influenza A viruses: combinations of hemagglutinin and neuraminidase subtypes isolated from animals and other sources. Archives of Virology 67(3): 191-201.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Descriptors:  antigens, viral classification, hemagglutinins viral classification, influenza A virus classification, neuraminidase immunology, birds microbiology, epitopes, horses microbiology, avian classification, human classification, influenza A virus immunology, swine microbiology, terminology.

Hioe, C.E., N. Dybdahl Sissoko, M. Philpott, and V.S. Hinshaw (1990). Overlapping cytotoxic T-lymphocyte and B-cell antigenic sites on the influenza virus H5 hemagglutinin. Journal of Virology 64(12): 6246-51.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To define the recognition site of cytotoxic T lymphocytes (CTLs) on influenza virus H5 hemagglutinin (HA), an H5 HA-specific CTL clone was examined for the ability to recognize monoclonal antibody-selected HA variants of influenza virus A/Turkey/Ontario/7732/66 (H5N9). On the basis of 51Cr release assays with the variants, a CTL epitope was located near residue 168 of H5 HA. To define the epitope more precisely, a series of overlapping peptides corresponding to this region was synthesized and tested for CTL recognition. The minimum peptide recognized by the CTL clone encompassed residues 158 to 169 of H5 HA. Relative to the H3 HA three-dimensional structure, this CTL epitope is located near the distal tip of the HA molecule, also known as a major B-cell epitope on H3 HA. A single mutation at residue 168 (Lys to Glu) in the H5 HA variants abolished CTL recognition; this same amino acid was shown previously to be critical for B-cell recognition (M. Philpott, C. Hioe, M. Sheerar, and V. S. Hinshaw, J. Virol. 64:2941-2947, 1990). Additionally, mutations within this region of the HA molecule were associated with attenuation of the highly virulent A/Turkey/Ontario/7732/66 (H5N9) (M. Philpott, B. C. Easterday, and V.S. Hinshaw, J. Virol. 63:3453-3458, 1989). When tested for recognition of other H5 viruses, the CTL clone recognized the HA of A/Turkey/Ireland/1378/83 (H5N8) but not that of A/Chicken/Pennsylvania/1370/83 (H5N2), even though these viruses contain identical HA amino acid 158-to-169 sequences. These results suggest that differences outside the CTL epitope affected CTL recognition of the intact HA molecule. The H5 HA site defined in these studies is, therefore, important in both CTL and B-cell recognition, as well as the pathogenesis of the virus.

            Descriptors:  B lymphocytes immunology, epitopes immunology, hemagglutinins viral immunology, influenza A virus avian immunology, T lymphocytes, cytotoxic immunology, amino acid sequence, cell line, chickens, cytotoxicity, immunologic, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, avian genetics, mice, mice inbred BALB c, molecular models, molecular sequence data, mutagenesis, site directed, protein conformation, turkeys, variation genetics.

Hirabayashi, T., H. Ochiai, S. Sakai, K. Nakajima, and K. Terasawa (1995). Inhibitory effect of ferulic acid and isoferulic acid on murine interleukin-8 production in response to influenza virus infections in vitro and in vivo.  Planta Medica 61(3): 221-6.  ISSN: 0032-0943.

            NAL Call Number:  450 P697

            Abstract:  We investigated the effect of ferulic acid (FA) and isoferulic acid (IFA), which are active components of the rhizoma of Cimicifuga species used frequently as anti-inflammatory drugs in Japanese Oriental medicines, on murine interleukin-8 (IL-8) production in response to influenza virus infections in vitro and in vivo by antibody-sandwich enzyme-linked immunosorbent assay. In the in vitro study, the murine macrophage cell line RAW 264.7 was infected with influenza virus at a dose of 10 plaque forming units (PFU)/cell and cultured in the presence or absence of drugs. Both FA and IFA reduced the IL-8 levels in the 20-h conditioned medium in comparison with control in a dose-dependent manner. The effect of IFA was greater than that of FA: IL-8 levels were reduced to 43% and 56% of the control in the presence of 100 micrograms/ml of IFA and FA, respectively. In the in vivo study, mice were infected with 1,000 PFU of virus and received daily oral administrations of Cimicifuga heracleifolia extract (5 mg/mouse/day), FA (0.5 mg/mouse/day), IFA (0.125 mg/mouse/day), or phosphate buffered saline. The three drugs showed a tendency to reduce IL-8 levels in bronchoalveolar lavage (BAL) obtained 2 days after infection. Moreover, both FA and IFA also significantly reduced the number of exuded neutrophils into BAL. However, the drug administrations did not affect the virus yields in BAL. These data suggest that FA and IFA are novel and potent inhibitors of murine IL-8 production and might act as one of the main components of anti-inflammatory rhizoma of Cimicifuga species.

            Descriptors:  cinnamates pharmacology, coumaric acids pharmacology, influenza immunology, influenza A virus avian immunology, interleukin 8 biosynthesis, antihypertensive agents pharmacology, cell line, chick embryo, lipopolysaccharides pharmacology, lung virology, macrophages drug effects, macrophages immunology, mice, mice inbred ICR, neutrophils drug effects, neutrophils physiology, medicinal plants, plants.

Hiti, A.L., A.R. Davis, and D.P. Nayak (1981). Complete sequence analysis shows that the hemagglutinins of the H0 and H2 subtypes of human influenza virus are closely related. Virology 111(1): 113-24.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus human immunology, amino acid sequence, base sequence, DNA, viral, avian immunology, human classification, human genetics.

Hof, H. and H.J. Gerth (1972). Independence of release of influenza A viruses from protein synthesis. Brief report. Archiv Fur Die Gesamte Virusforschung 37(2): 293-6.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  hemagglutinins viral biosynthesis, orthomyxoviridae metabolism, chick embryo, cycloheximide pharmacology, fibroblasts microbiology, hemadsorption, hemagglutination tests, influenza A virus avian growth and development, avian isolation and purification, avian metabolism, orthomyxoviridae growth and development, orthomyxoviridae isolation and purification, time factors, tissue culture, viral proteins biosynthesis.

Hoffmann, E., S. Krauss, D. Perez, R. Webby, and R.G. Webster (2002). Eight-plasmid system for rapid generation of influenza virus vaccines. Vaccine 20(25-26): 3165-70.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Descriptors:  genetic vectors genetics, influenza A virus avian genetics, human genetics, influenza vaccine biosynthesis, reassortant viruses genetics, antigenic variation genetics, birds virology, cell line, chick embryo, China, Czechoslovakia, DNA, recombinant genetics, dogs, genes viral, avian immunology, avian isolation and purification, human immunology, human isolation and purification, influenza vaccine genetics, influenza vaccine immunology, influenza vaccine isolation and purification, New Caledonia, Panama, phenotype, reassortant viruses immunology, reassortant viruses isolation and purification, reproducibility of results, reverse transcriptase polymerase chain reaction, transfection, virus cultivation.

Hoffmann, E., G. Neumann, Y. Kawaoka, G. Hobom, and R.G. Webster (2000). A DNA transfection system for generation of influenza A virus from eight plasmids. Proceedings of the National Academy of Sciences of the United States of America 97(11): 6108-13.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  We have developed an eight-plasmid DNA transfection system for the rescue of infectious influenza A virus from cloned cDNA. In this plasmid-based expression system, viral cDNA is inserted between the RNA polymerase I (pol I) promoter and terminator sequences. This entire pol I transcription unit is flanked by an RNA polymerase II (pol II) promoter and a polyadenylation site. The orientation of the two transcription units allows the synthesis of negative-sense viral RNA and positive-sense mRNA from one viral cDNA template. This pol I-pol II system starts with the initiation of transcription of the two cellular RNA polymerase enzymes from their own promoters, presumably in different compartments of the nucleus. The interaction of all molecules derived from the cellular and viral transcription and translation machinery results in the generation of infectious influenza A virus. The utility of this system is proved by the recovery of the two influenza A viruses: A/WSN/33 (H1N1) and A/Teal/HK/W312/97 (H6N1). Seventy-two hours after the transfection of eight expression plasmids into cocultured 293T and MDCK cells, the virus yield in the supernatant of the transfected cells was between 2 x 10(5) and 2 x 10(7) infectious viruses per milliliter. We also used this eight-plasmid system for the generation of single and quadruple reassortant viruses between A/Teal/HK/W312/97 (H6N1) and A/WSN/33 (H1N1). Because the pol I-pol II system facilitates the design and recovery of both recombinant and reassortant influenza A viruses, it may also be applicable to the recovery of other RNA viruses entirely from cloned cDNA.

            Descriptors:  DNA, complementary genetics, viral genetics, influenza A virus avian genetics, human genetics, plasmids genetics, transfection methods, base sequence, cell line, dogs, avian growth and development, human growth and development, molecular sequence data, promoter regions genetics, RNA polymerase I genetics, polymerase II genetics, messenger biosynthesis, RNA viral biosynthesis, recombination, genetic, regulatory sequences nucleic acid, transcription, genetic.

Holt, P. and J. Latimer (1989). Stimulatory effects of avian influenza virus on chicken lymphocytes. FASEB Journal, Federation of American Societies for Experimental Biology 3(4): A1340.

            NAL Call Number:  QH301.F3

            Descriptors:  lymphocytes, avian influenza virus, chicken.

Holt, P.S. (1990). Enhancement of chicken lymphocyte activation and lymphokine release by avian influenza virus. Developmental and Comparative Immunology 14(4): 447-55.  ISSN: 0145-305X.

            NAL Call Number:  QR180.D4

            Abstract:  We had previously found that inactivated avian influenza virus (AIV) could enhance the response of chicken lymphocytes to mitogen or antigen activation. An investigation into the possible mechanisms of this enhancement was undertaken. Peripheral blood lymphocytes (PBL) were incubated with AIV expressing different hemagglutinin (HA) types (H1-H13) along with doses of concanavalin A (Con A) which induce maximum (0.5 microgram) or submaximum (0.125 microgram) PBL activation. The lymphocyte activation was measured 72 h later. All of the HA types except H13 enhanced the Con A response. Diminished but significant enhancement could be observed when AIV administration was delayed by as much as 48 h of the 72-h incubation time. The AIV A/ck/Ala/75 (H4N8) was also examined for its effect on interleukin 2 (IL 2) synthesis by Con A-activated PBL and was found to modestly increase the synthesis of this lymphokine. All of the AIV hemagglutinin types agglutinated the PBL with titers slightly lower than that observed for the chicken erythrocyte agglutination. These results indicate that the AIV-induced enhancement of Con A responsiveness by chicken PBL is due, at least partly, to increased synthesis of IL 2 and that the effect may be due to some viral component other than the agglutinin.

            Descriptors:  influenza A virus avian immunology, interleukin 2 secretion, lymphocyte activation, agglutination, chickens, concanavalin a pharmacology, hemagglutination, viral, avian classification, lymphocytes immunology, species specificity.

Holt, P.S. and J.W. Latimer (1989). Stimulatory effect of avian influenza virus on chicken lymphocytes. Avian Diseases 33(4): 743-9.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  A study was conducted to examine the effect of avian influenza virus (AIV) on chicken lymphocyte activation. Unprimed or Brucella abortus antigen (Ag)-primed lymphocytes were incubated with various doses of the T-cell mitogen concanavalin A (Con A) or Ag, respectively, plus serial dilutions of inactivated AIV for 72 hr, and cell proliferation was measured via uptake of tritiated thymidine. AIV enhanced the proliferative response to Con A or Ag by 150% or better, and the enhancement decreased in a viral dose-dependent manner. The effects were more readily observed in cells that had not been maximally activated by the Con A or Ag. The enhanced response was observed in lymphocytes from both white rock and white leghorn breeds of chicken and in mature peripheral blood lymphocytes or immature thymocytes. The viral activity could be abrogated by pre-treatment of the viral preparation with AIV-specific antisera or prior adsorption of the AIV with chicken erythrocytes. These results indicate that AIV can interact with and modify the in vitro activity of chicken lymphocytes and may exert modulatory effects on the avian immune system.

            Descriptors:  chickens immunology, lymphocyte activation immunology, lymphocytes immunology, orthomyxoviridae pathogenicity, chickens microbiology, concanavalin A, erythrocytes immunology, specific pathogen free organisms.

Hooper, P.T. (1989). Lesions in chickens experimentally infected with 1985 H7N7 avian influenza virus. Australian Veterinary Journal 66(5): 155-156.  ISSN: 0005-0423.

            NAL Call Number:  41.8 Au72

            Abstract:  In groups receiving intranasal inoculations, 22 of 24 birds became affected. Illnesses were usually less than 2 d with clinical signs generally depression and dullness. Examination of lesions showed that this strain of virus produced in the laboratory a consistent, characteristic disease pattern, affecting predominantly the bursa of Fabricius, the pancreas and the brain.

            Descriptors:  chickens, avian influenza virus, wounds, pathology, birds, domestic animals, domesticated birds, Galliformes, influenza virus, lesions, livestock, poultry, useful animals, viruses.

Hooper, P.T., G.W. Russell, P.W. Selleck, and W.L. Stanislawek (1995). Observations on the relationship in chickens between the virulence of some avian influenza viruses and their pathogenicity for various organs. Avian Diseases 39(3): 458-464.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Comparative histological and immunocytochemical studies were conducted on formalin-fixed tissues from chickens infected with avian influenza viruses of varying virulence. Results showed a distinct pattern of disease that depended on the virulence of the virus and the susceptibility of the birds. At 3 days post-intranasal inoculation with a highly virulent H7N7 virus, all 6-to-8-week-old specific-pathogen-free (SPF) birds were affected, and all developed pancreatic necrosis and encephalitis associated with specific immunoperoxidase staining. Other same-aged SPF birds were only occasionally affected 6 to 8 days after intravenous inoculation with almost avirulent H4N4, H6N2, or H3N8 virus. Specific lesions and immunoperoxidase staining were noted in the kidneys only. The H7N7 virus in older commercial birds and an H7N3 virus in young SPF and older commercial birds caused intermediate mortality rates at 4 to 11 days postinoculation, and there was a broad range of lesions and specific immunoperoxidase staining in the pancreas, brain, kidney, heart, and skeletal muscle. Two exceptional birds had immunostaining of small blood vessels throughout their bodies with or without lesions or staining in the tissues, which may have represented a transitory pre-localizing phase occurring in many birds. There was necrosis without virus antigen detection in the bursae, thymuses, and cecal tonsils, possibly secondary to stress or only transitory infection of virus. These data indicate that rapid, retrospective diagnosis of avian influenza in fixed tissues is possible by using an immunoperoxidase test on pancreas, brain, and kidney.

            Descriptors:  chickens, avian influenza virus, pathogenicity, disease resistance, body parts, animal tissues, antigens, histopathology, immunology, biological properties, birds, body parts, domestic animals, domesticated birds, Galliformes, immunological factors, influenza virus, livestock, microbial properties, orthomyxoviridae, pathology, poultry, resistance to injurious factors, useful animals, viruses, susceptibility, viral antigens, immunocytochemistry.

Horimoto, T., T. Ito, D.J. Alexander, and Y. Kawaoka (1995). Cleavability of hemagglutinin from an extremely virulent strain of avian influenza virus containing a unique cleavage site sequence. Journal of Veterinary Medical Science the Japanese Society of Veterinary Science 57(5): 927-30.  ISSN: 0916-7250.

            NAL Call Number:  SF604.J342

            Abstract:  An avian influenza virus, A/turkey/England/50-92/91 (H5N1), showed extremely high virulence in chickens, although its hemagglutinin (HA) cleavage site sequence (R-K-R-K-T-R), having a nonbasic (Thr) residue at the second position (P-2) from the carboxyl terminus of HA1, does not conform to the previously established consensus sequence motif, X-X-R/K-X-R/K-R (X = nonbasic residue), for highly virulent phenotype of the H5 virus. When we evaluated the HA cleavability of this strain in chicken embryo fibroblast culture, we observed that, unlike other HAs with a Thr residue at P-2, this HA was efficiently cleaved. These findings suggest that a nonbasic residue at the P-2 does not affect its recognition and catalyzation by cleavage enzymes that are otherwise influenced by steric structure around the cleavage site.

            Descriptors:  chickens virology, fowl plague virology, hemagglutinins viral metabolism, influenza A virus avian pathogenicity, turkeys virology, amino acid sequence, cultured cells, chick embryo, fibroblasts cytology, fibroblasts virology, hemagglutinins viral chemistry, molecular sequence data, virulence.

Horimoto, T. and Y. Kawaoka (1997). Biologic effects of introducing additional basic amino acid residues into the hemagglutinin cleavage site of a virulent avian influenza virus. Virus Research 50(1): 35-40.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  We mutated the virulent avian influenza virus A/turkey/Ontario/7732/66 (H5N9)[Q-R-R-R-K-K-R?G at the hemagglutinin (HA) cleavage site] to create a mutant, R(MO-0), with additional basic residues at this site (Q-R-R-R-R-R-K-K-R?G) by reverse genetics. When tested in chicken embryo fibroblast culture, this mutant showed reduced HA cleavability compared to that of the wild-type virus, but its plaque size was not appreciably altered. Virulence of the R(MO-0) virus in chickens was lower than that of the wild-type virus. These findings indicate that addition of excessive basic residues to an optimal recognition sequence for HA cleavage enzymes at the cleavage site is deleterious for HA cleavability. Previously, we showed that a mutant containing the suboptimal HA cleavage site sequence for cleavage enzyme recognition also had reduced HA cleavability and virulence compared to the wild-type virus. We conclude that the data presented here further substantiate our belief that the level of HA cleavability correlates with the degree of virulence when all other genetic characteristics are considered equal, irrespective of the mechanisms by which HA cleavability is reduced.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian genetics, avian pathogenicity, administration, intranasal, chick embryo, chickens, fowl plague virology, hemagglutinins viral chemistry, hemagglutinins viral genetics, avian chemistry, injections, intramuscular, mutagenesis, site directed, plaque assay.

Horimoto, T. and Y. Kawaoka (1995). The hemagglutinin cleavability of a virulent avian influenza virus by subtilisin-like endoproteases is influenced by the amino acid immediately downstream of the cleavage site. Virology 210(2): 466-470.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Many viral membrane glycoproteins are post-translationally processed by intracellular endoproteases such as subtilisin-like proteases. These proteases recognize a cleavage site sequence comprising basic amino acids positioned upstream of the cleavage site of the viral proteins. Here, we mutated the glycine residue immediately downstream of the cleavage site (P1) of hemagglutinin (HA) from a virulent avian influenza virus, A/turkey/Ontario/7732/66 (H5N9) (R-R-R-K-K-R/G), to examine the effect of this mutation on its cleavability. Substitution of Gly with Ile, Leu, Val, or Pro, but not Ala, Asp, Phe, His, Ser, or Thr, resulted in substantial reduction of HA cleavage by endogenous endoproteases in CV-1 cells and by vaccinia-expressed PC6 and, albeit to a lesser extent, furin. We conclude that HA cleavage by subtilisin-like proteases is influenced by the downstream P1 amino acid in the absence of upstream cleavage site sequence alterations.

            Descriptors:  avian influenza virus, agglutinins, chemical composition, mutation, proteases, proteolysis, pathogenicity, biological properties, chemical reactions, enzymes, genetics, hydrolases, hydrolysis, influenza virus, microbial properties, orthomyxoviridae, proteins, viruses, viral hemagglutinins, amino acid sequences, proteinases, virulence.

Horimoto, T. and Y. Kawaoka (1995). Molecular changes in virulent mutants arising from avirulent avian influenza viruses during replication in 14-day-old embryonated eggs. Virology 206(1): 755-759.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The emergence of virulent avian influenza viruses in poultry is unpredictable. To gain insight into the mechanism for this event, we sought to identify the molecular changes in virulent mutants that occur during replication in 14-day-old embryonated chicken eggs. After three passages in 14-day-old eggs, avirulent H5 viruses with the K/R-K-K/T-R sequence at the hemagglutinin (HA) cleavage site became virulent in chickens, concomitantly acquiring high HA cleavability, whereas those with the R-E-T-R sequence did not. None of the test viruses converted to a virulent phenotype when passaged in 10-day-old eggs. Nucleotide sequence analysis indicated that the virulent mutants either lost a glycosylation site near the HA cleavage site or acquired an additional arginine at the latter. Avirulent viruses that became virulent after passage in older eggs included an H5N2 avian strain with the R-K-T-R sequence that was isolated in 1993, indicating that viruses with this sequence motif, which are currently circulating in bird populations, should be considered potentially virulent. Failure to generate virulent mutants from viruses with R-E-T-R at the HA cleavage site underscores the pathogenic heterogeneity among avian influenza viruses.

            Descriptors:  chicks, avian influenza virus, pathogenicity,  mutants, agglutinins, nucleotide sequence, chemical composition, biological properties, birds, chickens, domestic animals, domesticated birds, Galliformes, genomes, influenza virus, livestock, microbial properties, orthomyxoviridae, poultry, progeny, proteins, useful animals, viruses, young animals,  virus replication, cleavage site, virulence, viral hemagglutinins, amino acid sequences.

Horimoto, T. and Y. Kawaoka (1998). A possible mechanism for selection of virulent avian influenza A viruses in 14-day-old embryonated eggs. Journal of Veterinary Medical Science the Japanese Society of Veterinary Science 60(2): 273-5.  ISSN: 0916-7250.

            NAL Call Number:  SF604.J342

            Abstract:  The emergence of virulent avian influenza viruses in poultry is unpredictable. To gain insight into the mechanism of this event, we previously examined the possible role of older (14-day-old) embryonated eggs, in which virulent mutants were preferably selected (Horimoto and Kawaoka, Virology 206: 755-759, 1995). However, it is unknown why virulent mutants replicate predominantly in older eggs. In the present study, we compared protease activities responsible for cleavage activation of the hemagglutinin (HA) in allantoic fluids in 10-day and 14-day-old eggs. In vitro assays showed that the protease activities were stronger in the 14-day-old than 10-day-old eggs. The allantoic fluids with strong protease activity degraded HA. These results indicate that replication of avirulent viruses is hampered in older eggs, while that of virulent viruses whose HAs are activated by other intracellular proteases was not, possibly leading to a replicative advantage for virulent mutants in the older eggs.

            Descriptors:  influenza A virus avian pathogenicity, avian physiology, virulence, virus replication, allantois physiology, allantois virology, chick embryo, chickens, endopeptidases metabolism, glycosylation, hemagglutinins viral chemistry, hemagglutinins viral genetics, hemagglutinins viral physiology, avian isolation and purification, kinetics, mutation, polymerase chain reaction, substrate specificity.

Horimoto, T. and Y. Kawaoka (1994). Reverse genetic provides direct evidence for a correlation of hemagglutinin cleavability and virulence of an avian influenza A virus. Journal of Virology 68(5):  3120-3128.  ISSN:  0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To obtain direct evidence for a relationship between hemagglutinin (HA) cleavability and the virulence of avian influenza A viruses, we generated a series of HA cleavage mutants from a virulent virus, A/turkey/ Ontario/7732/66 (H5N9), by reverse genetics. A transfectant virus containing the wild-type HA with R-R-R-K-K-R at the cleavage site, which was readily cleaved by endogenous proteases in chicken embryo fibroblasts (CEF), was highly virulent in intramuscularly or intranasally/orally inoculated chickens. By contrast, a mutant containing the HA with an avirulent-like sequence (R-E-T-R) at the cleavage site, which was not cleaved by the proteases in CEF, was avirulent in chickens, indicating that a genetic alteration confined to the HA cleavage site can affect cleavability and virulence. Mutant viruses with HA cleavage site sequences of T-R-R-K-K-R or T-T-R-K-K-R were as virulent as viruses with the wild-type HA, whereas a mutant with a two-amino-acid deletion but retention of four consecutive basic residues (R-K-K-R) was as avirulent as a virus with the avirulent-type HA. Interestingly, although a mutant containing an HA with R-R-R-K-T-R, which has reduced cleavability in CEF, was as virulent as viruses with high HA cleavability when given intramuscularly, it was less virulent when given intranasally/orally. We conclude that the degree of HA cleavability in CEF predicts the virulence of avian influenza viruses.

            Descriptors:  chickens, avian influenza virus, agglutinins, proteolysis, mutants, induced mutation, pathogenicity, biological properties, birds, chemical reactions, domestic animals, domesticated birds, Galliformes, genetics, hydrolysis, influenza virus, livestock, microbial properties, mutation, poultry, progeny,  proteins, useful animals, viruses, posttranslational proteolysis, viral hemagglutinins, amino acid sequences.

Horimoto, T., K. Nakayama, S.P. Smeekens, and Y. Kawaoka (1994). Proprotein-processing endoproteases PC6 and furin both activate hemagglutinin of virulent avian influenza viruses. Journal of Virology 68(9): 6074-6078.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Among the proprotein-processing subtilisin-related endoproteases, furin has been a leading candidate for the enzyme that activates the hemagglutinin (HA) of virulent avian influenza viruses. In the present study, we examined the cleavage activity of two other recently isolated ubiquitous subtilisin-related proteases, PACE4 and PC6, using wild-type HA of A/turkey/Ireland/1378/83 (H5N8) and a series of its mutant HAs. Vaccinia virus-expressed wild-type HA was not cleaved in human colon adenocarcinoma LoVo cells, which lack active furin. This processing defect was correlated by the expression of furin and PC6 but not of PACE4 and a control wild-type vaccinia virus. PC6 showed a sequence specificity similar to that with the endogenous proteases in cultured cells. When LoVo cells were infected with a virulent avian virus, A/turkey/Ontario/7732/66 (H5N9), only noninfectious virions were produced because of the lack of HA cleavage. However, when the cells were coinfected with vaccinia virus that expressed either furin or PC6, the avian virus underwent multiple cycles of replication, indicating that both furin and PC6 specifically cleave the virulent virus HA at the authentic site. These data suggest that PC6, as well as furin, can activate virulent avian influenza virus in vivo implying the presence of multiple HA cleavage enzymes in animals.

            Descriptors:  avian influenza virus, agglutinins, proteolysis, proteases, chemical reactions, enzymes,  hydrolases, hydrolysis, influenza virus, proteins, viruses, proteolytic activation, proteolytic cleavage, viral hemagglutinins, precursors, proteinases.

Horimoto, T., E. Rivera, J. Pearson, D. Senne, S. Krauss, Y. Kawaoka, and R.G. Webster (1995). Origin and molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in Mexico. Virology 213(1): 223-230.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  In October of 1993, there was decreased egg production and increased mortality among Mexican chickens, in association with serologic evidence of an H5N2 influenza virus. First isolated from chickens in May of 1994, after spreading widely in the country, the virus caused only a mild respiratory syndrome in specific pathogen-free chickens. Because eradication of the virus by destruction of infected birds posed major obstacles to the poultry industry in Mexico, we were able to conduct a "field experiment" to determine the fate of an avirulent virus after repeated cycles of replication in millions of chickens. By the end of 1994, the virus had mutated to contain a highly cleavable hemagglutinin (HA), but remained only mildly pathogenic in chickens. Within months, however, it had become lethal in poultry. Nucleotide sequence analysis of the HA cleavage site of the original avirulent strain revealed R-E-T-R, typical of avirulent viruses and unlike the K-K-K-R sequence characterizing viruses responsible for the 1983 outbreak in poultry in the United States. Both mildly and highly pathogenic isolates contained insertions and a substitution of basic residues in the HA connecting peptide, R-K-R-K-T-R, which made the HA highly cleavable in trypsin-free chicken embryo fibroblasts. Phylogenetic analysis of the HA of H5 avian influenza viruses, including the Mexican isolates, indicated that the epidemic virus had originated from the introduction of a single virus of the North American lineage into Mexican chickens. This sequence of events demonstrates, apparently for the first time, the stepwise acquisition of virulence by an avian influenza virus in nature.

            Descriptors:  chickens, Mexico, United States, avian influenza virus, agglutinins, pathogenicity, chemical composition, phylogeny, America, biological properties, birds, domestic animals, domesticated birds, evolution, Galliformes, influenza virus, Latin America, livestock, microbial properties, North America, orthomyxoviridae, poultry, proteins, useful animals, viruses, cleavage site, viral hemagglutinins, virulence, amino acid sequences, outbreaks.

Horisberger, M.A. (1982). Identification of a catalytic activity of the large basic P polypeptide of influenza virus. Virology 120(2): 279-86.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, RNA viral biosynthesis, viral proteins metabolism, base sequence, cytidine triphosphate metabolism, DNA directed RNA polymerases metabolism, guanosine triphosphate metabolism, kinetics, mutation, messenger biosynthesis, temperature.

Horisberger, M.A., G.K. McMaster, H. Zeller, M.G. Wathelet, J. Dellis, and J. Content (1990). Cloning and sequence analyses of cDNAs for interferon- and virus-induced human Mx proteins reveal that they contain putative guanine nucleotide-binding sites: functional study of the corresponding gene promoter. Journal of Virology 64(3): 1171-81.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The human protein p78 is induced and accumulated in cells treated with type I interferon or with some viruses. It is the human homolog of the mouse Mx protein involved in resistance to influenza virus. A full-length cDNA clone encoding the human p78 protein was cloned and sequenced. It contained an open reading frame of 662 amino acids, corresponding to a polypeptide with a predicted molecular weight of 75,500, in good agreement with the Mr of 78,000 determined on sodium dodecyl sulfate gels for the purified natural p78 protein. The cloned gene was expressed in vitro and corresponded in size, pI, antigenic determinant(s), and NH2 terminus sequence to the natural p78 protein. A second cDNA was cloned which encoded a 633-amino-acid protein sharing 63% homology with human p78. This p78-related protein was translated in reticulocyte lysates where it shared an antigenic determinant(s) with p78. A putative 5' regulatory region of 83 base pairs contained within the gene promoter region upstream of the presumed p78 mRNA cap site conferred human alpha interferon (IFN-alpha) inducibility to the cat reporter gene. The p78 protein accumulated to high levels in cells treated with IFN-alpha. In contrast, the p78-related protein was not expressed at detectable levels. The rate of decay of p78 levels in diploid cells after a 24-h treatment with IFN-alpha was much slower than the rate of decay of the antiviral state against influenza A virus and vesicular stomatitis virus, suggesting that the p78 protein is probably not involved in an antiviral mechanism. Furthermore, we showed that these proteins, as well as the homologous mouse Mx protein, possess three consensus elements in proper spacing, characteristic of GTP-binding proteins.

            Descriptors:  DNA genetics, gtp binding proteins, genes, structural, guanine nucleotides metabolism, influenza A virus genetics, interferon type I, recombinant pharmacology, promoter regions genetics, proteins genetics, vesicular stomatitis Indiana virus genetics, virus inhibitors genetics, amino acid sequence, base sequence, binding sites, cell line, cloning, molecular, DNA isolation and purification, Escherichia coli genetics, gene library, influenza A virus avian genetics, molecular sequence data, molecular weight, proteins biosynthesis, proteins metabolism, RNA, messenger genetics, sequence homology, nucleic acid, transcription, genetic.

Huang Jianwen, Jiang Yanfen, and He Weimin (2002). Effects of the transfer factor on artificial infected chickens by AIV. Journal of Gansu Agricultural University (China). Gansu Nongye Daoxue Xuebao (China) 37(2): 170 173.  ISSN: 1003-4315.

            NAL Call Number:  S471.C62K352

            Descriptors:  transfer factor, avian influenza virus, chickens.

Huang, R.T. (1974). Adsorption of influenza virus to charged groups on natural and artificial surfaces. Medical Microbiology and Immunology 159(2): 129-35.  ISSN: 0300-8584.

            Descriptors:  adsorption, influenza A virus avian immunology, anions, cations, divalent, cations, monovalent, erythrocytes, hemagglutination.

Huang, R.T. (1976). Labeling of animal cells with fluorescent dansyl cerebroside. Zeitschrift Fur Naturforschung. Section C Biosciences 31(11-12): 737-40.  ISSN: 0341-0382.

            NAL Call Number:  QH301.Z4

            Abstract:  A dansyl (diaminoaphthalenesulfonyl)-derivative of cerebroside was prepared which could be effectively incorporated into the plasma membranes of tissue culture cells and erythrocytes. The cells which had assimilated the glycolipid fluoreced intensely and could be observed under a fluorescent microscope. Cells were initially labeled rather homogeneously over the whole surface. With longer incubation time organization of the fluorescent glycolipid took place and patches of the lipid in the membrane were formed. The redistribution and organization of the membrane lipid could be demonstrated most clearly when cells labeled with this fluorescent glycolipid were infected with myxoviruses. After infection of MDBK and BHK cells with fowl plaque virus areas of dense fluorescence appeared at margines of neighboring cells. When BHK cells were infected with Newcastle disease virus fusion of the cells was accompanied by complete redistribution of the glycolipid. Erythrocytes could also easily incorporate dansyl cerebroside. Chicken erythrocytes which contain cytoplsmic and nuclear membranes incorporated the fluorescent glycolipid in both membranes.

            Descriptors:  cerebrosides blood, dansyl compounds, erythrocytes metabolism, binding sites, cell line, cell membrane metabolism, cell membrane ultrastructure, chickens, erythrocyte membrane metabolism, erythrocyte membrane ultrastructure, fluorescent dyes, influenza A virus avian, Newcastle disease virus, spectrometry, fluorescence.

Huang, R.T. (1991). On the penetration mechanism of influenza viruses. Behring Institute Mitteilungen (89): 23-6.  ISSN: 0301-0457.

            NAL Call Number:  QR180.B4

            Abstract:  The envelopes of influenza viruses contain in addition to lipids also two glycoproteins, the hemagglutinin and the neuraminidase, that are responsible for the adsorption, receptor splitting, penetration and budding processes of these viruses. In this article, hypotheses presented in the past with regard to the virus penetration are reconsidered. Based on results obtained with the fowl plague virus (influenza A/FPV/Rostock/34, H7N1) and MDCK-cells, we conclude that a fusion between the viral envelope and the plasma membrane is the initial step of virus entry.

            Descriptors:  influenza A virus avian physiology, membrane fusion, cell line, cell membrane physiology, hemagglutination, viral envelope proteins metabolism.

Huang, R.T. (1976). On the structure of the carbohydrate chains of different strains of the influenza virus. Medical Microbiology and Immunology 162(3-4): 169-73.  ISSN: 0300-8584.

            Abstract:  Structural features of the glycosyl chains of the influenca virus have been determined. It was found that fucose was solely terminal, whereas mannose and galactose were present at the terminal as well as subterminal and core positions. Mannose and glucose molecules were shown to be branching points in the glycosyl chains. Furthermore, linkage positions of carbohydrates within the chains were characterized.

            Descriptors:  carbohydrates analysis, influenza A virus avian analysis, orthomyxoviridae analysis, fucose analysis, galactose analysis, glucose analysis, mannose analysis.

Huang, R.T. (1983). The role of neutral glycolipids and phospholipids in myxovirus-induced membrane fusion. Lipids 18(7): 489-92.  ISSN: 0024-4201.

            NAL Call Number:  QP751.L5

            Abstract:  Myxoviruses (influenza virus and paramyxovirus) enter host cells by two successive steps consisting of attachment and fusion between viral and cellular membranes. The initial attachment is known to occur through specific binding of the viruses with the neuraminic acid-containing receptors of cellular membranes. Evidence is presented here that, in the following step of membrane fusion, neutral glycolipids terminating in galactose and certain phospholipids (primarily lecithin and sphingomyelin) interact with the viral envelopes and that this interaction may be fundamental to the fusion process.

            Descriptors:  cell membrane physiology, glycolipids physiology, influenza A virus avian physiology, membrane lipids physiology, parainfluenza virus 1, human physiology, phospholipids physiology, receptors, virus physiology,  chick embryo, glycolipids pharmacology, hemolysis drug effects, phospholipids pharmacology, receptors, virus drug effects.

Huang, R.T. (1976). Sphingolipids of influenza viruses. Biochimica Et Biophysica Acta 424(1): 90-7.  ISSN: 0006-3002.

            NAL Call Number:  381 B522

            Abstract:  Total lipid of four egg grown influenza viruses (A2-Asia, A2-England, A2-Taiwan and fowl plague virus) were extracted with chloroform-methanol. After mild alkali treatment of the extracts, glycosphingolipids and sphingomyelin were separated by a silicic acid column, and finally purified by thin layer chromatography. Fatty acid, sphingosine and carbohydrate components of individual lipid classes were then analysed by gas-liquid chromatography. Nearly identical results were obtained with all viruses investigated. Approximately 20% of the total lipid was monohexosylceramide, distributed equally between glucosyl- and galactosyl- analogues. Lactosylceramide and oligohexosylceramides were found in much smaller concentrations (approx. 2%). About 15% of the total lipid was attributed to sphingomyelin. A large proportion of fatty acids (around 25% in sphingomyelin and 60% in glycolipids) belonged to the long chain (C19-C26) normal- and 2-hydroxy series. C18-sphingosine was found to be the only base present in all lipid classes investigated.

            Descriptors:  influenza A virus avian analysis, orthomyxoviridae analysis, sphingolipids analysis, fatty acids analysis, hexoses analysis, oligosaccharides analysis, sphingomyelins analysis.

Huang, R.T. and E. Dietsch (1988). Anti-influenza viral activity of aspirin in cell culture. New England Journal of Medicine 319(12): 797.  ISSN: 0028-4793.

            NAL Call Number:  448.8 N442

            Descriptors:  antiviral agents pharmacology, aspirin pharmacology, influenza A virus avian drug effects, human drug effects, cultured cells.

Huang, R.T., E. Dietsch, and R. Rott (1985). Further studies on the role of neuraminidase and the mechanism of low pH dependence in influenza virus-induced membrane fusion. Journal of General Virology 66(Pt. 2): 295-301.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The role of neuraminidase and the mechanism of low pH dependence in influenza virus-induced membrane fusion have been studied further using fowl plague virus (FPV, H7N1). Two specific anti-FPV neuraminidase antisera obtained from chickens immunized with recombinant virus strains inhibited viral neuraminidase activity without influencing its haemagglutinating activity. These sera totally inhibited the FPV-induced fusion of erythrocytes and partially reduced haemolysis. But both fusion and haemolysis activities could be restored by external addition of Vibrio cholerae neuraminidase, indicating participation of neuraminidase in FPV-induced membrane fusion. With regard to low pH-dependent fusion by influenza virus, it was found that erythrocytes of various species showed different pH optima for haemolysis by FPV and that erythrocytes could be sensitized for fusion and haemolysis by FPV at neutral pH if they had been pretreated with a low pH buffer. These results demonstrated that surface properties of erythrocytes rather than that of the virus are critical in the low pH-dependent fusion and haemolysis by influenza viruses.

            Descriptors:  cell fusion, influenza A virus avian physiology, neuraminidase physiology, viral proteins physiology, bacterial proteins physiology, chick embryo, erythrocytes, hemagglutination, viral, hemolysis, hydrogen-ion concentration, rabbits, rats, Vibrio cholerae enzymology.

Huang, R.T., B. Lichtenberg, and O. Rick (1996). Involvement of annexin V in the entry of influenza viruses and role of phospholipids in infection. FEBS Letters 392(1): 59-62.  ISSN: 0014-5793.

            NAL Call Number:  QD415.F4

            Abstract:  Influenza viruses bind to annexin V, a widely spread non-glycosylated phospholipid-binding protein. Externally added phospholipids as well as antiserum against this protein specifically inhibit infection of these viruses in cell cultures. We conclude that annexin V plays an important role in the entry of these viruses.

            Descriptors:  annexin V metabolism, influenza A virus avian metabolism, human metabolism, phospholipids metabolism, receptors, virus metabolism, antibodies, viral immunology, capsid metabolism, cell line, dogs, avian immunology, avian pathogenicity, human immunology, human pathogenicity, phosphatidylethanolamines metabolism, plaque assay, recombinant fusion proteins metabolism, time factors, viral core proteins metabolism.

Huang, R.T. and M. Orlich (1972). Substrate specificities of the neuraminidases of Newcastle disease and fowl plague viruses. Hoppe Seyler's Zeitschrift Fur Physiologische Chemie 353(3): 318-22.  ISSN: 0018-4888.

            NAL Call Number:  384 Z38

            Descriptors:  influenza A virus avian enzymology, neuraminidase, Newcastle disease virus enzymology, chickens, colloids, enzyme tests, gangliosides, glycolipids, hydrolysis, macromolecular systems, milk, human, oligosaccharides, structure activity relationship.

Huang, R.T., R. Rott, and H.D. Klenk (1973). On the receptor of influenza viruses. 1. Artificial receptor for influenza virus. Zeitschrift Fur Naturforschung. Teil C Biochemie, Biophysik, Biologie, Virologie 28(5): 342-5.  ISSN: 0341-0471.

            NAL Call Number:  QH301.Z4

            Descriptors:  glycoproteins metabolism, neuraminic acids metabolism, orthomyxoviridae metabolism, adsorption, binding sites, erythrocytes drug effects, hemagglutination, viral, hemagglutinins viral, influenza A virus avian metabolism, neuraminidase pharmacology, Newcastle disease virus metabolism, respirovirus metabolism, sindbis virus metabolism.

Huang, R.T., R. Rott, K. Wahn, H.D. Klenk, and T. Kohama (1980). The function of the neuraminidase in membrane fusion induced by myxoviruses. Virology 107(2): 313-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cell membrane physiology, glycoproteins physiology, influenza A virus avian immunology, neuraminidase physiology, Newcastle disease virus immunology, cultured cells, chick embryo, hemagglutinins viral metabolism, hemagglutinins viral physiology, liposomes metabolism, viral proteins metabolism, viral proteins physiology.

Huang, R.T., K. Wahn, H.D. Klenk, and R. Rott (1980). Fusion between cell membrane and liposomes containing the glycoproteins of influenza virus. Virology 104(2): 294-302.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cell membrane physiology, hemagglutinins viral, influenza A virus avian physiology, human physiology, orthomyxoviridae physiology,  cultured cells, chick embryo, glycoproteins,  liposomes, microinjections, receptors, virus physiology, viral proteins.

Huang, R.T., K. Wahn, M.F. Schmidt, and R. Rott (1981). Productive infection of chick embryo cells by influenza viruses tightly bound on substratum. Medical Microbiology and Immunology 170(2): 91-8.  ISSN: 0300-8584.

            Abstract:  To test whether penetration of influenza viruses could occur at the plasma membrane of host cells, virus particles were tightly bound on Concanavalin A-coated substratum of plastic culture plates and then overlayed with embryo cells. Under these conditions, endocytosis of the viruses was prevented but the cells were found to be effectively infected. The results indicate, that infection by influenza viruses can occur through fusion between the viral membrane and the host cell plasma membrane.

            Descriptors:  cell membrane permeability, influenza A virus avian physiology, orthomyxoviridae physiology, cultured cells, chick embryo, endocytosis, avian ultrastructure, microscopy, electron, virus cultivation methods.

Hulse, D.J., R.G. Webster, R.J. Russell, and D.R. Perez (2004). Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens. Journal of Virology 78(18): 9954-64.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  influenza A virus, avian genetics, avian pathogenicity, viral matrix proteins genetics, base sequence, chickens, DNA, viral genetics, glycosylation, hemagglutinins, viral chemistry, viral genetics, avian classification, influenza, avian etiology, models, molecular, neuraminidase chemistry, neuraminidase genetics, viral matrix proteins chemistry, virulence genetics.

Iamnikova, S.S., E.A. Dubova, I.G. Shemiakin, M.K.h. Saiatov, and D.K. L'vov (1984). Selektsiia antigennykh variantov virusos grippa H1N1 posredstvom monoklonal'nykh antitel. [Selection of antigenic variants of H1N1 influenza viruses by means of monoclonal antibodies]. Voprosy Virusologii 29(2): 207-10.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Six different monoclonal antibodies to influenza A/Brazil/11/78 virus hemagglutinin were used for selection of antigenic variants of H1N1 viruses: A/USSR/090/77 and A/black-headed gull/ Kaz . SSR/470/79. The group-specific monoclonal antibody completely neutralized the infective activity of the parental viruses (dilutions 1:5 to 1:640). Two antigenic variants of wild type viruses were obtained using cross-reactive antibody. A comparative study of the antigenic structure, biological properties, and peptide maps of the heavy chain of the original viruses, antigenic variants, and some epidemic H1N1 strains was carried out. The selected variants of A/black-headed gull/ Kaz. SSR/470/77 and A/USSR/090/79 viruses were shown to be similar to epidemic H1N1 strains isolated in 1953 and 1978.

            Descriptors:  antibodies, monoclonal analysis, antigens, viral isolation and purification, influenza A virus human immunology, selection genetics, variation genetics, antigens, viral analysis, birds, cross reactions, electrophoresis, polyacrylamide gel, hemagglutination inhibition tests, avian immunology, peptides analysis.

Iamnikova, S.S., T.O. Kovtun, G.A. Dmitriev, I.G. Shemiakin, N.P. Semenova, D.K. L'vov, T. Chambers, and R. Vebster (1989). Antigennaia varibel'nost' virusov grippa ptits A/H13, izolirovannykh v SSSR. [Antigenic variability of avian influenza virus A/H13, isolated in the USSR]. Voprosy Virusologii 34(5): 568-72.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The antigenic structure of influenza H13 viruses isolated from wild birds in the USSR in 1976-1985 was studied. Antiserum against the reference A/gull/Maryland/704/77 (H13N6) strain was used to demonstrate the antigenic variations among the viruses. The homology of nucleotide sequences in the region 99-215 for the two A/H13N6 strains, A/gull/Maryland/704/77 and A/great black-headed gull/Astrakhan/227/84, were 75% and 86%, respectively. The 9-base segment deletion in A/grey black-headed gull/Astrakhan/277/84 was observed. Comparison of the predicted amino acid sequences of the strains' hemagglutinin in the appropriate region (amino acids 2-40) revealed 5 replacements (86% homology). Two replacements of arginine by lysine and asparagine by serine in positions 15 and 16, respectively, are the most significant. The latter replacement is accompanied by a change in the glycosylation site and might alter its three-dimensional structure. Further studies of the isolate genome are under way.

            Descriptors:  antigenic variation, antigens, viral immunology, influenza A virus avian immunology, amino acid sequence, antigens, viral genetics, base sequence, hemagglutinins viral genetics, avian genetics, molecular sequence data, radioimmunoassay, sequence homology, nucleic acid, viral proteins analysis.

Ilyushina, N.A., I.A. Rudneva, N.L. Varich, A.S. Lipatov, R.G. Webster, and N.V. Kaverin (2003). Antigenic structure of influenza A virus H5 hemagglutinin: Mechanisms of the acquisition of resistance towards monoclonal antibodies in escape mutants.  Molekuliarnaia Genetika, Mikrobiologiia i Virusologiia (1): 40-45.  ISSN: 0208-0613.

            NAL Call Number:  QH506.M65F2

            Abstract:  The analysis of escape mutants of the avian influenza virus of H5 subtype (strain A/Mallard/Pennsylvania/10218/84) revealed the location and structure of two antigenic sites in the hemagglutinin (HA) molecule. Several escape mutants exhibited unusual features in the reactions with monoclonal antibodies (Mabs), being completely resistant in the infectivity neutralization test to the Mabs used for their selection, and retaining the ability to bind the Mabs as revealed by enzyme-linked immunosorbent assay. An enhancement of the binding by an amino acid change in a different antigenic site was demonstrated, as well as a complete abolishment of the binding by a mutation selected by passage in the presence of an excess of the non-neutralizing Mab of high binding ability. The observed effects did not result from the changes in the affinity of the mutant HA toward sialic receptors. The data suggest that one amino acid change in HA may prevent the virus neutralization by different mechanisms for different Mabs: either the binding of the Mab to HA is prevented, or the bound Mab is unable to block the receptor-binding pocket of HA. Different mechanisms of the acquisition of resistance to Mabs in the course of the selection of escape mutants are discussed.

            Descriptors:  immune system, infection, methods and techniques, molecular genetics, ELISA immunologic techniques, laboratory techniques, virus infectivity neutralization test bioassay techniques, laboratory techniques, gene mutations, methodology, viral genetics, viral neutralization, mechanisms, analysis.

Imai, M., A. Takada, K. Okazaki, and H. Kida (1999). Antigenic and genetic analyses of H5 influenza viruses isolated from ducks in Asia. Japanese Journal of Veterinary Research 46(4): 171-7.  ISSN: 0047-1917.

            NAL Call Number:  41.8 V6446

            Abstract:  The hemagglutinin (HA) of six H5 influenza virus strains isolated from ducks in Japan and China in 1976 to 1996 were analyzed antigenically and genetically. Antigenic analysis using a panel of monoclonal antibodies revealed that the HA of H5 influenza viruses isolated from ducks are antigenically closely related to each other. Phylogenetic analysis indicates that the isolates from ducks in Hokkaido were derived from an ancestor common with the highly pathogenic isolates from chickens and humans in Hong Kong in 1997.

            Descriptors:  ducks virology, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian classification, avian genetics, phylogeny, antibodies, monoclonal, antigens, viral genetics, viral immunology, chickens virology, China, genes viral, hemagglutinin glycoproteins, influenza virus immunology, Hong Kong, avian isolation and purification, Japan, RNA viral genetics, viral isolation and purification.

Indulen, M.K. and R.L. Feldblum (1982). Obtaining of a virazole-resistant fowl plague virus mutant. Acta Virologica 26(1-2): 109.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  influenza A virus avian genetics, human genetics, mutation, ribavirin pharmacology, ribonucleosides pharmacology, drug resistance, fowl plague microbiology, influenza microbiology, phenotype.

Indulen, M.K. and V.A. Kalninya (1973). Study on the mechanism of inhibiting action of aminoadamantane on the reproduction of fowl plague virus. Acta Virologica 17(4): 273-80.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  amantadine pharmacology, influenza A virus avian metabolism, RNA viral biosynthesis, autoradiography, carbon radioisotopes, cultured cells, chick embryo, dactinomycin pharmacology, avian drug effects, avian growth and development, plaque assay, tissue culture, tritium, uridine metabolism, virus replication drug effects.

Indulen, M.K., V.A. Kalnynia, N.V. Gorodkova, and F.L. Fel'dblium (1986). Molekuliarno-biologicheskii analiz mutantov i rekombinantov virusov grippa, rezistentnykh k remantidinu. [Molecular biology analysis of influenza virus mutants and recombinants resistant to remantadine]. Voprosy Virusologii 31(5): 609-13.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  adamantane analogs and derivatives, influenza A virus avian drug effects, human drug effects, mutation, recombination, genetic drug effects, rimantadine antagonists and inhibitors, antigens, viral analysis, chick embryo, drug resistance, microbial genetics, genes viral drug effects, avian genetics, avian immunology, human genetics, human immunology, plaque assay.

Inglis, S.C. and J.W. Almond (1980). An influenza virus gene encoding two different proteins. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 288(1029): 375-81.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  Evidence is presented which confirms that the influenza virus genome specifies a polypeptide of molecular mass 11 000, in addition to the eight previously recognized gene products. A summary is included of results that show that this polypeptide is encoded by the smallest genome segment of the virus (segment 8) which also encodes a polypeptide of molecular mass 23 000 (NS1). The implications of these findings are considered.

            Descriptors:  genes viral, influenza A virus avian genetics, viral proteins genetics, cultured cells, chickens, genes, structural, molecular weight, species specificity.

Inglis, S.C. and C.M. Brown (1984). Differences in the control of virus mRNA splicing during permissive or abortive infection with influenza A (fowl plague) virus. Journal of General Virology 65(Pt. 1): 153-64.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Spliced transcripts of influenza A (fowl plague) virus (FPV) RNA (vRNA) segments 7 and 8 accumulate to a much greater extent during non-productive infection of mouse L cells, than they do during productive infection in primary chick embryo fibroblasts (CEF). Virus-specific protein synthesis, or a consequent event in virus replication appears necessary to promote splicing of vRNA segment 8-encoded mRNAs in both cell types, and of vRNA segment 7-encoded mRNAs in CEF. In L cells, however, splicing of the segment 7-encoded mRNAs seems to be independent of such virus-specific control. This observation is discussed in relation to the defect in expression of vRNA 7 which has been observed previously in FPV-infected L cells, and which is thought to account for the failure of virus replication.

            Descriptors:  fowl plague microbiology, influenza A virus avian genetics, RNA splicing, RNA viral genetics, chick embryo, DNA genetics, viral genetics, gene expression regulation, l cells cell line microbiology, mice, nucleic acid hybridization, peptides genetics, viral proteins biosynthesis, virus cultivation, virus replication.

Inglis, S.C. and C.M. Brown (1981). Spliced and unspliced RNAs encoded by virion RNA segment 7 of influenza virus. Nucleic Acids Research 9(12): 2727-40.  ISSN: 0305-1048.

            NAL Call Number:  QD341.A2N8

            Abstract:  Cells infected with the avian influenza virus fowl plague virus, contains three species of polyadenylated RNA which are complementary to virion RNA segment 7. The largest is virtually a complete transcript of vRNA 7, and is the messenger RNA for the matrix protein, but the coding function of the two smaller species, which are approximately 320 and 285 nucleotides long (excluding poly(A)), is unknown. It is likely however that at least one of the small RNAs encodes a new virus polypeptide which has been predicted from the nucleotides sequence of vRNA 7. The major part of each RNA maps within about 300 nucleotides from the 5'-terminus of vRNA 7, but the larger species also contains additional sequences derived from the 3' terminus. Production of the two small RNAs may involve alternative patterns of splicing of the matrix protein mRNA.

            Descriptors:  DNA, viral genetics, influenza A virus avian genetics, poly A genetics, RNA genetics, chick embryo, cloning, molecular, DNA restriction enzymes, fibroblasts, RNA, messenger genetics, transcription, genetic, translation, genetic, viral proteins genetics.

Inglis, S.C., A.R. Carroll, R.A. Lamb, and B.W. Mahy (1976). Polypeptides specified by the influenza virus genome I. Evidence for eight distinct gene products specified by fowl plague virus. Virology 74(2): 489-503.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, translation, genetic, viral proteins biosynthesis, cultured cells, hemagglutinins viral, influenza A virus avian enzymology, molecular weight, neuraminidase biosynthesis, nucleoproteins biosynthesis, peptide synthesis, peptides analysis, RNA replicase, viral proteins analysis.

Inglis, S.C., M.J. Gething, and C.M. Brown (1980). Relationship between the messenger RNAs transcribed from two overlapping genes of influenza virus. Nucleic Acids Research 8(16): 3575-89.  ISSN: 0305-1048.

            NAL Call Number:  QD341.A2N8

            Abstract:  The relationship of the mRNAs encoding the NS1 and NS2 polypeptides of influenza virus has been investigated through synthesis and characterisation of complementary DNA copies of the mRNAs. Previous work had shown that both mRNAs are encoded by virion RNA segment 8, and that the sequences comprising the smaller of the two mRNAs (the NS2 mRNA) were also present on the NS1 mRNA. Our results indicate that the mRNA encoding the NS2 polypeptide of the avian influenza, fowl plague virus, is approximately 400 ntds long, and that its sequences correspond largely with the 3'-terminal region of the NS1 mRNA.

            Descriptors:  DNA, viral metabolism, genes, structural, orthomyxoviridae metabolism, RNA, messenger biosynthesis, transcription, genetic, nucleic acid hybridization, peptide synthesis, translation, genetic, viral proteins biosynthesis.

Inglis, S.C. and B.W. Mahy (1979). Polypeptides specified by the influenza virus genome. 3. Control of synthesis in infected cells. Virology 95(1): 154-64.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, RNA, messenger biosynthesis, viral biosynthesis, viral proteins biosynthesis, cell line, cycloheximide pharmacology, genes viral, avian genetics, transcription, genetic, translation, genetic.

Inglis, S.C., D.J. McGeoch, and B.W. Mahy (1977). Polypeptides specified by the influenza virus genoma. 2. Assignement of protein coding functions to individual genome segments by in vitro translation. Virology 78(2): 522-36.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, peptide synthesis, RNA, messenger metabolism, RNA viral metabolism, translation, genetic, viral proteins biosynthesis, cell free system, genetic code, glycoproteins biosynthesis, hemagglutinins viral, triticum.

Inkster, M.D., V.S. Hinshaw, and I.T. Schulze (1993). The hemagglutinins of duck and human H1 influenza viruses differ in sequence conservation and in glycosylation. Journal of Virology 67(12): 7436-43.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  We determined the deduced amino acid sequences of two H1 duck influenza A virus hemagglutinins (HAs) and found that the consensus sequence of the HA, determined directly from virus recovered from the intestinal tract, remains unchanged through many generations of growth in MDCK cells and chicken embryos. These two duck viruses differ from each other by 5 amino acids and from A/Dk/Alberta/35/1976 (F. J. Austin, Y. Kawaoka, and R. G. Webster, J. Gen. Virol. 71:2471-2474, 1990) by 9 and 12 amino acids, most of which are in the HA1 subunit. They are antigenically similar to each other but different from the Alberta virus. We compared these H1 duck HAs with the HAs of human isolates to identify structural properties of this viral glycoprotein that are associated with host range. By comparison to the human H1 HAs, the duck virus HA sequences are highly conserved as judged by the small fraction of nucleotide differences between strains which result in amino acid substitutions. However, the most striking difference between these duck and human HAs is in the number and distribution of glycosylation sites. Whereas duck and swine viruses have four and five conserved glycosylation sites per HA1 subunit, none of which are on the tip of the HA, all human viruses have at least four additional sites, two or more of which are on the tip of the HA. These findings stress the role of glycosylation in the control of host range and suggest that oligosaccharides on the tip of the HA are important to the survival of H1 viruses in humans but not in ducks or swine.

            Descriptors:  consensus sequence genetics, ducks microbiology, hemagglutinins viral genetics, influenza A virus avian genetics, human genetics, amino acid sequence, antigens, viral genetics, antigens, viral immunology, cultured cells, consensus sequence immunology, feces microbiology, glycosylation, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, avian immunology, human immunology, models, molecular, molecular sequence data, protein processing, post translational, regulatory sequences, nucleic acid genetics, selection genetics, sequence homology, amino acid, variation genetics.

Inpanbutr, N. and R.D. Slemons (1993). Immunocytochemical localization of type A influenza virus nucleoprotein in chicken kidney, using freeze substitution technique for tissue fixation. American Journal of Veterinary Research 54(3): 425-8.  ISSN: 0002-9645.

            NAL Call Number:  41.8 Am3A

            Abstract:  Kidney tissues were removed from euthanatized mature White Leghorn chickens 4 days after IV inoculation with type A influenza virus. The kidney tissues were then fixed at -70 C, using a freeze substitution technique. Type A influenza virus nucleoprotein was readily detected in the nuclei and cytoplasm of the proximal and distal tubular epithelial cells by immunocytochemistry, and the sharpness of the immunomarker in the cells indicated minimal antigen migration during fixation and tissue section preparation. This tissue fixation technique also resulted in good preservation of cellular morphology. The freeze substitution technique of tissue fixation is an excellent alternative to cryostat-cut acetone-fixed tissue sections or conventional chemical fixation of paraffin-embedded tissues for in situ immunocytochemical localization of type A influenza virus nucleoprotein antigen.

            Descriptors:  influenza A virus avian isolation and purification, kidney microbiology, nucleoproteins analysis, chick embryo, chickens, epithelium microbiology, freezing, immunohistochemistry, kidney tubules microbiology.

Isachenko, V.A., S.S. Iamnikova, L.I.a. Zakstel'skaia, T.A. Grigor'eva, and O.N. Berezina (1980). Vyiavlenie determinant gemaggliutinina H3 virusov grippa metodom radioimmunologicheskogo analiza. [Detection of the determinants of influenza virus H3 hemagglutinin by the technic of radioimmunologic analysis]. Voprosy Virusologii (1): 49-53.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The interrelations between H3/73 hemagglutinin of human influenza virus and the other 16 mammalian and avian hemagglutinin subtypes (a total of 50 strains) were studied by the method of radioimmunologic analysis (RIA). The antigenic relations of H3, Hav7 and Heq2 were confirmed, certain common determinants were also found in H3/73 hemagglutinin and avian viral Hav6 and Hav9 hemagglutinins. No interrelations were revealed with previously circulating human influenza viruses H0, H1, H2 as well as with swine influenza virus and avian viruses Hav1-Hav5, Hav8. It has been shown that the H3/73 determinant in some avian viruses evolves similarly to drift-variants of human influenza virus. The method can be recommended for fine analysis of influenza virus antigenic structure as it allows detecting small antigenic quantities.

            Descriptors:  hemagglutinins viral immunology, influenza A virus immunology, ducks microbiology, avian immunology, human immunology, porcine immunology, species specificity, turkeys microbiology, radioimmunologic analysis.

Isaeva, E.I., T.S. Belkina, Z.I. Rovnova, P.N. Kosiakov, and I.A.M. Selivanov (1982). Antigennye determinanty virusov grippa cheloveka v sostave grippoznykh virusov, vydelennykh ot zhivotnykh. [Antigenic determinants of human influenza viruses among the influenza viruses isolated from animals]. Voprosy Virusologii 27(6): 681-6.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Comparative studies of the antigenic properties of hemagglutinin (HA) of animal and human viruses revealed both similarities between them and complete differences in the composition of antigenic determinants. Avian influenza viruses A/chicken/Kamchatka/12/71, A/pintail/Primorie/730/76, and A/bat/Alma-Ata/73/77 were completely identical with human strains of influenza virus. Influenza A/horse/Miami/63 contains one antigenic determinant H3.1.HA of A/tern/Turkmenia/18/73 (Hav7) viruses has a peculiar set of antigens. Apart from two antigenic determinants H3.1 and H3.3 inherent in human virus strains, HA of A/tern/Turkmenia/18/73 virus contains an antigenic determinant the population of antibodies to which shows no relation to HA of subtypes Hav2-Hav9.

            Descriptors:  epitopes isolation and purification, influenza A virus human immunology, orthomyxoviridae immunology, complement fixation tests, epitopes analysis, hemagglutination inhibition tests, hemagglutinins viral analysis, hemagglutinins viral isolation and purification, immunoelectrophoresis, orthomyxoviridae isolation and purification.

Israel, A. (1980). Genotypic and phenotypic characterization of a mammalian cell-adapted mutant of fowl plague virus (FPV). Journal of General Virology 51(Pt. 1): 33-44.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  A mammalian cell-adapted mutant of the Dobson strain of fowl plague virus (FPV-B) was characterized. Genetic analyses of recombinants between a ts mutant of this virus and either the non-adapted Dobson strain or the Rostock strain of FPV showed that the gene coding for the P3 protein of the adapted Dobson strain was sufficient to enable any recombinant to grow in L cells. The abortive cycle of wild-type Dobson strain (FPV+) was compared to the productive cycle of the mutant. By using 100 p.f.u./cell, no quantitative difference could be detected in infected L cells between polypeptides and cRNAs induced by FPV+ and FPV-B. However, the maturation of virions at the plasma membrane did not proceed correctly. At a lower m.o.i. the amounts of virus polypeptides decreased with the m.o.i. This decrease was not the same for all polypeptides and cRNA segments: HA, M and NA and their mRNAs decreased to a greater extent than the others. These results are discussed in relation to a possible biological activity of polypeptide P3.

            Descriptors:  genes viral, influenza A virus avian genetics, virus replication, avian growth and development, avian metabolism, L cells cell line, mice, mutation, RNA viral biosynthesis, recombination, genetic, viral proteins biosynthesis.

Israel, A. (1979). Preliminary characterization of the particles from productive and abortive infections of L cells by fowl plague virus. Annales De Microbiologie 130b(1): 85-100.  ISSN: 0300-5410.

            NAL Call Number:  448.3 An75

            Abstract:  Particles produced during the abortive infection of L cells by fowl plague virus (Dobson strain) have been characterized and compared to the infectious particles produced by a mutant of this virus adapted to mammalian cells. The former are of apparently normal morphology but most of them are non-infectious. They have the same RNA/protein ratio as the infectious particles and the same polypeptide composition. They contain also the same RNA segments as those found in infectious particles. Possible reasons for the defectiveness of these particles are discussed.

            Descriptors:  influenza A virus avian analysis, l cells cell line microbiology, virion analysis, electrophoresis, polyacrylamide gel, hemagglutinins analysis, avian ultrastructure, peptides analysis, RNA viral analysis, viral proteins analysis, virion ultrastructure.

Israel, A. (1980). Productive and abortive infection of L cells by fowl plague virus (FPV): comparison of in vivo and in vitro translation products of the virus mRNAs. Journal of General Virology 47(2): 473-83.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The abortive infection of L cells by the Dobson strain of fowl plague virus (FPV) and the productive infection by a mammalian cell-adapted mutant have been compared. The mRNA population during the abortive cycle is characterized by a lower production compared to the productive system of mRNA 7 (which codes for the M polypeptide) early in the cycle, and a lower production of mRNAs 4, 6 and 7 (which code for HA, NA and M) late in the cycle. Differences in the amounts of the corresponding polypeptides can also be detected when these mRNA populations are used to programme a wheat germ cell-free system. However, analysis of the polypeptides synthesized in vivo by the two viruses show that equivalent amounts of all virus polypeptides are synthesized during the productive and the abortive cycles. Possible reasons for differences between in vivo and in vitro translation of the virus mRNAs during the abortive cycle are discussed.

            Descriptors:  influenza A virus avian metabolism, RNA, messenger biosynthesis, RNA viral biosynthesis, viral proteins biosynthesis, avian growth and development, L cells cell line, mice, RNA, messenger genetics, viral genetics, translation, genetic, viral proteins analysis.

Israel, A. (1980). A temperature-dependent host range mutant of fowl plague virus (FPV). Virology 105(1): 1-12.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian genetics, l cells cell line microbiology, chick embryo, dactinomycin pharmacology, electrophoresis, polyacrylamide gel, fluorouracil pharmacology, avian growth and development, mice, mutation, nucleic acid hybridization, peptide synthesis, plaque assay, RNA viral biosynthesis, temperature, viral proteins biosynthesis, virus cultivation, virus replication.

Israel, A., A. Niveleau, G. Quash, and M.H. Richard (1979). Latex fetuin spheres as probes for influenza virus neuraminidase in productively and abortively infected cells. Archives of Virology 61(3): 183-99.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Fetuin bound latex spheres do not adhere to the membranes of non-infected cells but adhere to those of cells productively infected by fowl plague virus (FPV Dobson strain). In contrast, asialo fetuin spheres do not attach to the membranes of productively infected cells. Moreover latex fetuin spheres incubated with extracts of productively infected cells and extensively washed are specifically enriched in neuraminidase activity without any trace of haemagglutinin. These observations suggest that viral neuraminidase in the membrane is the site of attachment of the sialic acid moieties of fetuin spheres. These neuraminidase sites are detectable when L cells are productively infected by a mammalian cell adapted mutant of the Dobson strain (FPV-B) but are not detectable on L cells abortively infected by wild type (FPV+). However, even in the abortive system, neuraminidase is synthesised de novo as shown by its labelling with 14C-glucosamine and by its isolation from labelled extracts of infected cells by latex fetuin spheres. These results show that misintegration of viral neuraminidase in the plasma membrane of L cells is a feature of abortive infection of these cells by the Dobson strain of FPV. However the relationship (if any) of this misintegration to abortive infection remains to be established.

            Descriptors:  cell membrane enzymology, influenza A virus avian enzymology, microbiological techniques, neuraminidase analysis, cell line, avian growth and development, l cells cell line, latex, microscopy, electron, scanning, microspheres, neuraminidase biosynthesis, alpha fetoproteins.

Israel, A., M. Semmel, and J. Huppert (1975). Host-range mutant of fowl plague virus (FPV): comparison of the genome and virus proteins. Virology 68(2): 503-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian growth and development, mutation, RNA viral analysis, viral proteins analysis, cell line, chickens, glycoproteins analysis, hamsters, avian analysis, mice, molecular weight, nucleic acid conformation, peptides analysis, virus replication.

Itamura, S. (2000). Development of influenza vaccines against newly emerging A/H5N1 virus. Nippon Rinsho Japanese Journal of Clinical Medicine 58(1): 255-64.  ISSN: 0047-1852.

            Abstract:  Emergence of highly virulent influenza A/H5N1 viruses in Hong Kong in 1997 posed a threat of pandemic and brought an urgent need to develop a suitable seed virus for vaccine production. The virulence of the H5N1 viruses to chicken embryos should hamper the efficient production of the vaccine. In addition, potential virulence to humans raised safety issue in manufacturing vaccine. Toward vaccine development, one approach is to use an avirulent avian influenza virus antigenically similar to the virulent ones as a surrogate vaccine strain. The other approach is based on the attenuation of pathogenicity of virulent H5N1 virus by genetic engineering of the hemagglutinin gene and selection of a gene constellation. The reverse genetics technique can make the latter approach possible. Candidate strains suitable for vaccine production could be prepared by using either approach.

            Descriptors:  influenza transmission, influenza A virus human genetics, human immunology, influenza vaccine, chick embryo, genes viral, genetic engineering, hemagglutinins chemistry, hemagglutinins genetics, vaccines, attenuated, virulence.

Itkin, Z.B. and Z.F. Bogautdinov (1973). Kharakteristika belkov virusa grippa ptits. [Characteristics of proteins of avian influenza virus]. Sbornik Nauchnykh Trudov, Moskovskaya Veterinarnaya Akademiya 70: 125-130.

            Descriptors:  proteins, avian influenza virus, electrophoresis.

Ito, T., H. Kida, and R. Yanagawa (1985). Antigenic analysis of H4 influenza virus isolates using monoclonal antibodies to defined antigenic sites on the hemagglutinin of A/Budgerigar/Hokkaido/1/77 strain. Archives of Virology 84(3-4): 251-9.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Three non-overlapping antigenic sites were defined on the hemagglutinin of avian influenza virus A/budgerigar/Hokkaido/1/77 (H4N6) by competitive binding assay of monoclonal antibodies to the virus and comparative antigenic analysis of variants selected with monoclonal antibodies. Antigenic relationship among 25 H4 influenza viruses of different bird origin was examined by ELISA with the monoclonal antibodies to each of defined antigenic sites. Two of the three antigenic sites contained epitopes specific to the H4 influenza viruses of budgerigar and mynah origin, and the remaining site contained an epitope which was cross-reactive with almost all of the H4 influenza viruses.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, antibodies, monoclonal, antibodies, viral, birds microbiology, chickens microbiology, cross reactions, ducks microbiology, enzyme linked immunosorbent assay, epitopes immunology, species specificity.

Ito, T., Y. Kobayashi, T. Morita, T. Horimoto, and Y. Kawaoka (2002). Virulent influenza A viruses induce apoptosis in chickens. Virus Research 84(1-2): 27-35.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Virulent avian influenza A viruses produce lethal disease in chickens. Since cell death can be caused by either necrosis or apoptosis, we investigated the types of cell death that occur in natural hosts, chickens, infected with virulent avian viruses. Using biochemical methods, we demonstrate that virulent avian influenza viruses induce apoptosis of vascular endothelial cells in liver, kidney, and brain. Viral antigens were also detected in these organs, suggesting that viral replication induces apoptosis in infected chickens. These results indicate that apoptosis does occur in virulent avian influenza virus infection in a natural host, and may contribute to the lethality of the virus.

            Descriptors:  apoptosis, influenza A virus avian pathogenicity, antigens, viral physiology, chickens, virulence.

Ito, T., Y. Suzuki, L. Mitnaul, A. Vines, H. Kida, and Y. Kawaoka (1997). Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species. Virology 227(2): 493-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Despite their uniform ability to bind to oligosaccharide-containing terminal sialic acids, influenza A viruses show differences in receptor specificity. To test whether agglutination of erythrocytes from different animal species could be used to assess the receptor specificity of influenza A viruses, we determined the agglutinating activities of a range of virus strains, including those with known receptor specificities, using erythrocytes from seven animal species. All equine and avian viruses, including those known to recognize N-acetyl and N-glycolyl sialic acid linked to galactose by the alpha2,3 linkage (NeuAc alpha2,3Gal and NeuGc alpha2,3Gal), agglutinated erythrocytes from all of the animal species tested (chickens, ducks, guinea pigs, humans, sheep, horses, and cows). The human viruses, including those known to preferentially recognize NeuAc alpha2,6Gal, agglutinated all but the horse and cow erythrocytes. Fluorescence-activated cell sorting analysis of erythrocytes using linkage-specific lectins [Sambucus nigra agglutinin for sialic acid (SA) alpha2,6Gal and Maackia amurensis agglutinin for SA alpha2,3Gal] showed that both cow and horse erythrocytes contain a large amount of SA alpha2,3Gal-, but virtually no SA2,6Gal-specific lectin-reactive oligosaccharides on the cell surface, while human and chicken erythrocytes contained both types of oligosaccharides. Considering that the majority (>93%) of sialic acid in horse and cow erythrocytes is of the N-glycolyl type, our results suggest that viruses able to agglutinate these erythrocytes (i.e., avian and equine viruses) recognize NeuGc alpha2,3Gal. These findings also show that agglutinating assays with erythrocytes from different animal species would be useful in characterizing the receptor specificity of influenza A viruses.

            Descriptors:  erythrocytes physiology, erythrocytes virology, hemagglutination, influenza A virus physiology, receptors, virus physiology,  carbohydrate sequence, cattle, chick embryo, chickens, guinea pigs, horses, influenza A virus avian physiology, human physiology, porcine, lectins, molecular sequence data, species specificity, substrate specificity, swine.

Ito, T., Y. Suzuki, T. Suzuki, A. Takada, T. Horimoto, K. Wells, H. Kida, K. Otsuki, M. Kiso, H. Ishida, and Y. Kawaoka (2000). Recognition of N-glycolylneuraminic acid linked to galactose by the alpha2,3 linkage is associated with intestinal replication of influenza A virus in ducks. Journal of Virology 74(19): 9300-5.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The hemagglutinin (HA) of H3 human influenza viruses does not support viral replication in duck intestine despite its avian origin. A Leu-to-Gln mutation at position 226 and a Ser-to-Gly mutation at position 228 in the HA of human A/Udorn/307/72 (H3N2) permit a reassortant virus [human Udorn HA, with all other genes from A/mallard/New York/6750/78 (H2N2)] to replicate in ducks. To understand the molecular basis of this change in host range restriction, we investigated the receptor specificity of duck influenza viruses as well as of human-duck virus reassortants. The results indicate that the recognition of a glycoconjugate moiety possessing N-glycolneuramic acid (NeuGc) linked to galactose by the alpha2,3 linkage (NeuGcalpha2,3Gal) is associated with viral replication in duck intestine. Immunofluorescence assays with NeuGcalpha2,3Gal-specific antiserum detected this moiety primarily on the crypt epithelial cells of duck colon. Such recognition, together with biochemical evidence of NeuGc in crypt cells, correlated exactly with the ability of the virus to replicate in duck colon. These results suggest that recognition of the NeuGcalpha2,3-Gal moiety plays an important role in the enterotropism of avian influenza viruses.

            Descriptors:  ducks virology, hemagglutinins viral physiology, influenza virology, influenza A virus physiology, neuraminic acids, galactose, virus replication.

Ito, T., H. Goto, E. Yamamoto, H. Tanaka, M. Takeuchi, M. Kuwayama, Y. Kawaoka, and K. Otsuki (2001). Generation of a highly pathogenic avian influenza A virus from an avirulent field isolate by passaging in chickens. Journal of Virology 75(9): 4439-4443.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Highly virulent avian influenza viruses can arise from avirulent strains maintained in poultry, but evidence to support their generation from viruses in wild birds is lacking. The most likely mechanism for the acquisition of virulence by benign avian viruses is the introduction of mutations by error-prone RNA polymerase, followed by the selection of virulent viruses. To investigate whether this mechanism could apply to wild waterfowl, we studied an avirulent wild-swan virus that replicates poorly in chickens. After 24 consecutive passages by air sac inoculation, followed by five passages in chicken brain, the avirulent virus became highly pathogenic in chickens, producing a 100% mortality rate. Sequence analysis at the hemmaglutinin cleavage site of the original isolate revealed a typical avirulence type of sequence, R-E-T-R, which progressed incrementally to a typical virulence type of sequence, R-R-K-K-R, during repeated passages in chickens. These results demonstrate that avirulent viruses maintained in wild waterfowl in nature and bearing the consensus avirulence type sequence R-E-T-R have the potential to become highly pathogenic while circulating in chickens.

            Descriptors:  molecular genetics, infection, veterinary medicine.

Ito, T., H. Ito, M. Kojima, and Y. Kawaoka (2004). Amino acids associated with intestinal replication of influenza A virus in ducks: relationship to low pH stability of neuraminidase. International Congress Series 1263: 205-208.

            Abstract:  In order to determine the role of neuraminidase (NA) in host range restriction, we studied a reassortant virus that replicated with poor efficiency in ducks. The reassortant virus, in which NA of an avian virus, A/duck/Hong Kong/278/78 (H2N9), was replaced with that from a human virus, A/England/12/62 (H2N2), was rectally inoculated into ducks. The viruses recovered were then orally inoculated into new ducks and a variant that replicated efficiently in the intestinal tract was isolated. Sequence analysis showed that the variant virus NA contained two amino acid substitutions at positions 165 (Val to Ile) and 431 (Gln to Pro). Differences in low pH resistance of the NAs were also assessed to identify differences in the NAs possibly related to the restriction of viral growth in ducks. The NA activity of the parental reassortant virus almost disappeared after low pH treatment (pH 3.0), while that of the variant was conserved under the same conditions. These results indicate that the amino acids, at positions 165 and/or 431 on the NA molecule, correlate with the ability to support viral growth in ducks, contributing to the low pH stability of NA activity.

            Descriptors:  avian influenza, intestinal replication, low pH, neuraminidase, ducks, amino acids, influenza A virus.

Ivanova, V., R. Rouseva, M. Kolarova, J. Serkedjieva, R. Rachev, and N. Manolova (1994). Isolation of a polysaccharide with antiviral effect from Ulva lactuca. Preparative Biochemistry (USA) 24(2): 83-97.  ISSN: 0032-7484.

            NAL Call Number:  QD415.A1P7

            Abstract:  A polysaccharide from the green marine algae Ulva lactuca has been isolated. The substance has been investigated after acid hydrolysis by thin-layer and gas chromatography. The following carbohydrate components have been found: arabinose-xylose-rhamnose-galactose-mannose-glucose in ratio 1:1:9:5:2.5:16 respectively. One unidentified sugar has been demonstrated too. The polysaccharide has been studied for antiviral activity in vitro against a number of human and avian influenza viruses. A considerable inhibition of the viral reproduction was found. The effect was dose-dependent, strain-specific and selective.

            Descriptors:  algae, chemical composition, polysaccharides, purification, monosaccharides, arabinose, xylose, rhamnose, galactose, mannose, glucose, aldoses, carbohydrates, monosaccharides, processing, reducing sugars, sugars, carbohydrate composition, composition.

Ivanova, V.T., H. Hermann, L.Y.A. Zakstelskaya, L. Dohner, R.Y.A. Podchernyaeva, and V.K. Blinova (1983). Differentiation of influenza A virus nucleoproteins in enzyme-linked immunosorbent assay. Acta Virologica 27(1): 71-4.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The serum antibody titre to the nucleoprotein (NP) of the influenza virus recombinant MRC-11 was determined in virus strains A/USSA/5/80 (H3N2), A/Hong Kong/8/64 (H3N2), A/duck/Ukraine/63 (Hav7Neq2) and in a recombinant strain between A/tern/Frunse/334/78(Hav4Nav1) and A/PR/8/34(H0N1) using the enzyme-linked immunosorbent assay (ELISA). Significant differences between the NP of these strains were found proving the usefulness for ELISA for such investigations.

            Descriptors:  antigens, viral analysis, influenza A virus avian analysis, human analysis, nucleoproteins immunology, viral proteins immunology, enzyme linked immunosorbent assay, avian immunology, human genetics, human immunology, recombination, genetic.

Ivanova, V.T., V.A. Isachenko, L.I.A. Zaktstel'skaia, and V.M. Zhdanov (1979). Sravnitel'noe izuchenie elektroforeticheskoi podvizhnosti polipeptidov virusov grippa roda a ptitis. [Comparative study of the electrophoretic mobility of the polypeptides from avian influenza viruses type A]. Voprosy Virusologii (5): 505-10.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A comparative study of the electrophoretic mobility of polypeptides of avian influenza viruses was carried out; molecular weights of polypeptides and their percent content were determined. Strains isolated from one host and possessing different hemagglutinin serotypes were found to have different electrophoregrams due to differences in the position of the light or heavy chain of hemagglutinin. Hemagglutinins (Hav7, Heq2, H3) and (Hav1, Heq1) in virions isolated from different hosts had similar electrophoretic mobilities of the heavy and particulary light chain. No significant variations in the molecular weights of NP and M proteins of all the viruses under study were found. No identity in the electrophoretic mobility and content of P1--P3 proteins in different strains of avian influenza virus was found.

            Descriptors:  influenza A virus avian analysis, peptides analysis, birds microbiology, chick embryo, electrophoresis, polyacrylamide gel, hemagglutinins viral analysis, molecular weight.

Iwasaki, T., S. Itamura, H. Nishimura, Y. Sato, M. Tashiro, T. Hashikawa, and T. Kurata (2004). Productive infection in the murine central nervous system with avian influenza virus A (H5N1) after intranasal inoculation. Acta Neuropathologica 108(6): 485-92.  ISSN: 0001-6322.

            Abstract:  The H5N1 type of influenza A virus isolated from human patients in 1997 has a characteristic hemagglutinin and was considered to be directly transmitted from birds. Although neuropathogenicity of this virus was not demonstrated in human autopsy cases, some experimental studies using mice have disclosed that this virus infects the central nervous system (CNS) after intranasal inoculation. In this study we focused on the topographical localization of virus-infected cells in the murine CNS after intranasal inoculation. We immunohistochemically examined virus-infected cells in mouse tissues using a rabbit antiserum recognizing the nucleoprotein of influenza A virus. The virus-infected cells appeared initially in the respiratory tract. Thereafter, the virus antigen-positive cells appeared in the olfactory system and the cranial nerve nuclei innervating the facial region. This suggests that this virus is principally transmitted from the nasal cavity to CNS through the cranial nerves. Neurons were frequently infected and glial and ependymal cells were also infected. Transneuronal transmission of the virus might play the important role of viral spread within the CNS.

            Descriptors:  central nervous system pathology, central nervous system virology, influenza A virus, avian influenza pathogenicity, nasal cavity virology, administration, intranasal, birds, immunohistochemistry, mice, neurons pathology.

Iwatsuki Horimoto, K., R. Kanazawa, S. Sugii, Y. Kawaoka, and T. Horimoto (2004). The index influenza A virus subtype H5N1 isolated from a human in 1997 differs in its receptor-binding properties from a virulent avian influenza virus. Journal of General Virology 85(Pt. 4): 1001-5.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  To gain insight into the events that occur when avian influenza viruses are transmitted to humans, the receptor-binding properties of the index H5N1 influenza virus isolated from a human in 1997 and the A/turkey/Ontario/7732/66 (H5N9) virus were compared, by using a haemadsorption assay. Cells expressing the haemagglutinin (HA) of the human isolate were adsorbed by both chicken red blood cells (RBCs) and human RBCs; those expressing the avian virus HA were only adsorbed by chicken RBCs. These results indicate that human and avian influenza virus H5 HAs differ in their recognition of sialyloligosaccharides on the RBCs of different animal species. Mutational analyses indicated that differences in both the oligosaccharide chains and in the amino acid sequences around the HA receptor-binding site were responsible for this difference in receptor binding. These data further support the concept that alteration in receptor recognition is important for replication of avian viruses in humans.

            Descriptors:  influenza A virus, avian physiology, human physiology, chickens, hemagglutinins, viral chemistry, viral genetics, hemagglutinins, viral physiology, avian pathogenicity, human genetics, human isolation and purification, human pathogenicity, models, molecular, mutagenesis, site directed, protein conformation, receptors, virus physiology, virulence, virus replication.

Jackson, D.C., L.E. Brown, and D.O. White (1981). Antigenic determinants of influenza virus haemagglutinin. VI. Antigenic characterization of the oligosaccharide sidechains form HA1 of influenza virus haemagglutinins. Journal of General Virology 52(Pt. 1): 163-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The oligosaccharide sidechains attached to the major polypeptide, HA1 of the haemagglutinin of influenza virus were examined for antigenic activity using a solid-phase radioimmunoassay. Cross-reactivity between the HA1 of the different human subtypes was clearly demonstrable with IgG raised against purified virus but was abrogated if anti-carbohydrate antibodies were first removed by passage of the IgG through an immunoadsorbent column containing haemagglutinin (HA) from an unrelated avian influenza strain. Antibodies eluted from the column were found to cross-react with the HA1 of all subtypes tested. 'Host antigen' extracted from chick chorioallantoic membrane and coupled to Sepharose was also able to remove cross-reactive antibodies from antiviral sera, while antibodies raised against host antigen bound to the HA1 isolated from each subtype tested. It is concluded that, although there are qualitative and quantitative differences between the oligosaccharide sidechains of influenza haemagglutinins, the antigenically active sidechains are cross-reactive.

            Descriptors:  hemagglutinins viral immunology, influenza A virus immunology, oligosaccharides immunology, cross reactions, epitopes, influenza A virus classification, radioimmunoassay.

Jackson, D.C., X.L. Tang, K.G. Murti, R.G. Webster, G.W. Tregear, and W.J. Bean (1991). Electron microscopic evidence for the association of M2 protein with the influenza virion. Archives of Virology 118(3-4): 199-207.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Immunogold electron microscopy revealed that site-specific antibodies elicited by a synthetic peptide representing the N-terminal sequence (residues 2-10) of influenza virus M2 protein were capable of binding to the surface of virions. Antibody binding was observed with two human influenza virus strains but not with an avian virus strain which has amino acid substitutions in the appropriate sequence of M2. These results provide direct evidence for the presence of M2 in the influenza virion.

            Descriptors:  orthomyxoviridae metabolism, viral matrix proteins metabolism, virion metabolism, amino acid sequence, influenza A virus avian metabolism, avian ultrastructure, human metabolism, human ultrastructure, influenza B virus metabolism, influenza B virus ultrastructure, influenza virus C metabolism, influenza virus C ultrastructure, microscopy, immunoelectron, molecular sequence data, orthomyxoviridae immunology, orthomyxoviridae ultrastructure, peptides chemical synthesis, peptides immunology, viral matrix proteins ultrastructure, virion ultrastructure.

Jameson, J., J. Cruz, M. Terajima, and F.A. Ennis (1999). Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species. Journal of Immunology 162(12): 7578-83.  ISSN: 0022-1767.

            NAL Call Number:  448.8 J8232

            Abstract:  Recently, an avian influenza A virus (A/Hong Kong/156/97, H5N1) was isolated from a young child who had a fatal influenza illness. All eight RNA segments were of avian origin. The H5 hemagglutinin is not recognized by neutralizing Abs present in humans as a result of infection with the human H1, H2, or H3 subtypes of influenza A viruses. Subsequently, five other deaths and several more human infections in Hong Kong were associated with this avian-derived virus. We investigated whether influenza A-specific human CD8+ and CD4+ T lymphocytes would recognize epitopes on influenza A virus strains derived from swine or avian species, including the 1997 H5N1 Hong Kong virus strains. Our results demonstrate that adults living in an urban area of the U.S. possess influenza A cross-serotype reactive CD8+ and CD4+ CTL that recognize multiple epitopes on influenza A viruses of other species. Bulk culture cytotoxicity was demonstrated against avian and human influenza A viruses. Enzyme-linked immunospot assays detected precursor CTL specific for both human CTL epitopes and the corresponding A/HK/97 viral sequences. We hypothesize that these cross-reactive CTL might provide partial protection to humans against novel influenza A virus strains introduced into humans from other species.

            Descriptors:  cd4 positive T lymphocytes immunology, CD4 positive T lymphocytes virology, CD8 positive T lymphocytes immunology, CD8 positive T lymphocytes virology, influenza A virus avian immunology, porcine immunology, cell line, chickens, cytotoxicity, immunologic genetics, ducks, enzyme linked immunosorbent assay, avian genetics, porcine genetics, leukocytes, mononuclear immunology, leukocytes, mononuclear virology, peptides genetics, peptides immunology, point mutation, stem cells immunology, stem cells virology, swine.

Ji DeJun, Peng DaXin, Liu HongQi, Chen SuJuan, Wu YanTao, Gao Song, and Liu XiuFan (2003). Genetic stability of a recombinant fowlpox virus with an avian influenza virus H9 hemaglutinin (HA) gene insert. Chinese Journal of Veterinary Science 23(4): 347-349.  ISSN: 1005-4545.

            NAL Call Number:  SF604.C58

            Descriptors:  antibodies, genetic stability, hemagglutinins, immunity, avian influenza virus, fowl pox virus, chickens.

Jia LiJun, Liu XiuFan, Zhang YanMei, Peng DaXin, and Zhang RuKuan (2004). Effect of rFPV-IFN- gamma as immunopotentiator on active immunization induced by H5 subtype avian influenza vaccines in chickens.  Journal of Agricultural Biotechnology 12(4): 427-430.  ISSN: 1006-1304.

            NAL Call Number:  S494.5.B563N86

            Descriptors:  immunity, immunization, inactivated vaccines, recombinant vaccines, interferon, maternal antibodies, potency, avian influenza virus, fowl pox virus, chickens.

Jia LiJun, Zhang YanMei, Peng DaXin, Liu HongQi, Cheng Jian, Zhang RuKuan, and Liu XiuFan (2004). Influence of dosage and maternal antibody on responses of chickens to recombinant fowl pox virus vaccine against H5 subtype avian influenza. Chinese Journal of Veterinary Science 24(2): 150-152.  ISSN: 1005-4545.

            NAL Call Number:  SF604.C58

            Descriptors:  chicks, immune response, immunization, dosage, maternal antibodies, mortality, recombinant vaccines, avian influenza, fowl pox virus.

Johansson, B.E. and E.D. Kilbourne (1993). Dissociation of influenza virus hemagglutinin and neuraminidase eliminates their intravirionic antigenic competition. Journal of Virology 67(10): 5721-3.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  When presented together on the intact influenza virus particle, the external hemagglutinin (HA) and neuraminidase (NA) antigens are competitive, with HA dominant over NA in both T- and B-cell priming (B. E. Johansson, T. M. Moran, and E. D. Kilbourne, Proc. Natl. Acad. Sci. USA 84:6869-6873, 1987). Dissociation and purification of HA and NA from virus and their injection separately or in combination into BALB/c mice eliminates their antigenic competition as measured by antibody response, confirming that it is their structural association that leads to what we have termed intravirionic antigenic competition. We discuss this phenomenon with respect to previously described intermolecular antigenic competition and with regard to its probable mechanism. Our findings are relevant to contemporary interest in viral vaccine vectors and multicomponent vaccines.

            Descriptors:  hemagglutinins viral immunology, influenza immunology, influenza A virus avian immunology, human immunology, neuraminidase immunology, antibodies, viral blood, antibody formation, enzyme linked immunosorbent assay, hemagglutination inhibition tests, hemagglutinin glycoproteins, influenza blood, avian pathogenicity, human pathogenicity, lung microbiology, mice, neutralization tests, viral envelope proteins immunology.

Joss, A., A.J. Hay, J.J. Skehel, and D.C. Burke (1968). Protein components of fowl-plague virus. Biochemical Journal 110(3): 40-41.  ISSN: 0264-6021.

            NAL Call Number:  QP501,B64

            Descriptors:  antigens analysis, influenza A virus avian analysis, proteins analysis, centrifugation, density gradient, electrophoresis, hemagglutinins viral analysis, tritium.

Jou, W.M., M. Verhoeyen, R. Devos, E. Saman, R. Fang, D. Huylebroeck, W. Fiers, G. Threlfall, C. Barber, N. Carey, and S. Emtage (1980). Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA. Cell 19(3): 683-96.  ISSN: 0092-8674.

            NAL Call Number:  QH573.C42

            Abstract:  The complete sequence of a hemagglutinin (HA) gene of a recent human influenza A strain, A/Victoria/3/75, is 1768 nucleotides long and contains the information for 567 amino acids. It codes for a signal peptide of 16 amino acids, the HA1 chain of the mature hemagglutinin of 329 amino acids, a connecting region between HA1 and HA2 consisting of a single arginine residue and the HA2 portion of 221 amiino acids. The sequence is compared with the hemagglutinin of two members of other subtypes, the human H2 strain A/Jap/305/57 and the avian Hav1 strain A/FPV/Rostock/34, and with one of the same H3 subtype, A/Memphis/3/72. To align the HA1 chain of different major subtypes several deletions/insertions of single amino acids must be invoked, but two more extensive differences are found at both ends, one leading to an extension of the amino terminal sequence of HA1 and the other (four residues) occurring in the region processed away between HA1 and HA2. Comparison of the HA1 of two H3 strains suggests that drift probably depends on single base mutations, some of which change antigenic determinants. The HA2 region, which apparently is not involved in the immune response, is highly conserved even between different subtypes, and single base substitutions account for all the observed diversity. A hydrophobic segment of 24 residues is present in the same position close to the carboxyl terminus of HA2 in both Victoria and FPV, and presumably functions in implantation into the lipid bilayer. The many conserved features not only in HA2 but also in HA1 suggest a rather rigid architecture for the whole hemagglutinin molecule.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus human genetics, RNA viral genetics, amino acid sequence, base sequence, carbohydrates analysis, cloning, molecular, codon, DNA, viral genetics, epitopes, hemagglutinins viral analysis, avian genetics.

Justewicz, D.M., M.J. Morin, H.L. Robinson, and R.G. Webster (1995). Antibody-forming cell response to virus challenge in mice immunized with DNA encoding the influenza virus hemagglutinin. Journal of Virology 69(12): 7712-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Immunization of mice with DNA encoding the influenza virus hemagglutinin (HA) affords complete protection against lethal influenza virus infection and the means to investigate the mechanisms of B-cell responsiveness to virus challenge. Using a single-cell enzyme-linked immunospot assay, we sought to determine the localization of HA-specific antibody-forming cells (AFCs) during the development of humoral immunity in mice given HA DNA vaccine by gene gun. At 33 days postvaccination, populations of AFCs were maintained in the spleen and bone marrow. In response to lethal challenge with influenza virus, the AFCs became localized at the site of antigenic challenge, i.e., within the draining lymph nodes of the lung compartment. Immunoglobulin G (IgG)- and IgA-producing AFCs were detected in lymph nodes of the upper and lower respiratory tracts, underscoring their importance in clearing virus from the lungs. Response to challenge required competent CD4+ T cells, without which no AFCs were generated, even those producing IgM. By contrast, in mice vaccinated with an HA-containing subunit vaccine, fewer AFCs were generated in response to challenge, and these animals were less capable of resisting infection. Our findings demonstrate the comparable localization of AFCs in response to challenge in mice vaccinated with either HA DNA or live virus. Moreover, the former strategy generates both IgG- and IgA-producing plasma cells.

            Descriptors:  B lymphocytes immunology, DNA, viral immunology, hemagglutinins viral genetics, influenza A virus avian immunology, influenza vaccine toxicity, T lymphocytes, helper inducer immunology, antibody formation, bone marrow immunology, CD4 positive T lymphocytes, viral metabolism, viral toxicity, hemagglutinin glycoproteins, influenza virus, viral biosynthesis, hemagglutinins viral immunology, immunization, secondary, immunologic memory, lethal dose 50, lymph nodes immunology, lymphocyte depletion, mice, spleen immunology, time factors.

Kaleta, E.F. and A. Honicke (2005). A retrospective description of a highly pathogenic avian influenza A virus (H7N1/Carduelis/Germany/72) in a free-living siskin (Carduelis spinus Linnaeus, 1758) and its accidental transmission to yellow canaries (Serinus canaria Linnaeus, 1758). DTW Deutsche Tierarztliche Wochenschrift 112(1): 17-9.  ISSN: 0341-6593.

            NAL Call Number:  41.8 D482

            Abstract:  A haemagglutinating virus was isolated in summer 1972 from a single free-living siskin (Carduelis spinus Linnaeus, 1758) in embryonated chicken eggs. Additional cases of morbidity or mortality were not observed in the area were the sick siskin was found. The virus was characterized as an avian influenza A virus of the subtype H7N1 and designated H7N1/Carduelis/Germany/72. The virus induced following experimental inoculation of chicken embryos a high rate mortality (mean death time approximately 24 hours), formed plaques in chicken embryo fibroblast cultures without addition of trypsin and has an intracerebral pathogenicity index (ICPI) of 1.80. Therefore, this virus is considered as a highly pathogenic avian influenza A virus. Canaries (Serinus canarius Linnaeus, 1758), that were housed in the same room with the siskin were accidentially exposed by contact to the sick siskin which resulted in virus transmission followed by conjunctivitis, apathy, anorexia and a high rate mortality.

            Descriptors:  canaries virology, disease transmission, horizontal veterinary, influenza A virus, avian pathogenicity, influenza, avian transmission, Passeriformes virology, retrospective studies.

Kaleta, E.F. and A. Honicke (2004). Review of the literature on avian influenza A viruses in pigeons and experimental studies on the susceptibility of domestic pigeons to influenza A viruses of the haemagglutinin subtype H7. DTW Deutsche Tierarztliche Wochenschrift 111(12): 467-72.  ISSN: 0341-6593.

            NAL Call Number:  41.8 D482

            Abstract:  The scientific literature of the past century is reviewed on fowl plague (presently termed highly pathogenic avian influenza, HPAI) in pigeons. HPAI viruses cause epidemic disease outbreaks with high rates of losses in many avian species, particularily in chickens and turkeys. Also susceptible to disease are quails, guinea fowl, ducks, geese, ostriches, passerine birds, and birds of prey whereas conflicting reports on the susceptibility of the domestic pigeon exist. Based on literature reports and on own experiments, and applying as criteria for judgements clinically overt forms of disease, virus multiplication plus shedding and seroconversion, it is concluded that domestic pigeons are only partially susceptible to influenza A viruses of the haemagglutinin subtype H7. Infection of pigeons with H7 viruses results only in some of them in signs, virus shedding and seroconversion. Using the same criteria, pigeons appear to be even less susceptible to infection with influenza A viruses of the H5 subtype. Only one of five publications describe in 1/19 pigeons exposed to H5 influenza A virus depression one day before death, and only 2/19 multiplied and excreted virus, and 1/19 developed circulating antibodies. Consequently, pigeons play only a minor role in the epidemiology of H5 influenza viruses. In contrast, following infection with influenza A virus of the subtype H7 clinical signs in pigeons consist of conjunctivitis, tremor, paresis of wings and legs, and wet droppings. H7-infected pigeons multiply and excrete H7 viruses and develop circulating antibodies. Albeit of the status of infection, free-flying domestic pigeons can act as mechanical vectors and vehicles for long-distance transmission of any influenza A virus if plumage or feet were contaminated.

            Descriptors:  Columbidae virology, influenza A virus, avian pathogenicity, avian influenza virology, chick embryo, chickens, disease susceptibility veterinary, ducks, avian classification, avian influenza pathology, avian influenza transmission, species specificity, virus shedding.

Kalninya, V.A. and M.K. Indulen (1976). Effect of adamantane derivatives on the activity of orthomyxovirus RNA-dependent RNA polymerase. Acta Virologica 20(4): 343-6.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The effect of several adamantane derivatives on the activity of virion-associated RNA-dependent RNA polymerase of fowl plague virus (FPV) and influenza B virus was studied in vitro. Some of the derivatives inhibited the activity of the polymerase by 60 per cent. A correlation was established between the previously demonstrated capacity of these inhibitors to suppress orthomyxovirus reproduction in vivo and their ability to reduce the activity of virion-associated RNA-dependent RNA polymerase in vitro.

            Descriptors:  adamantane pharmacology, bridged compounds pharmacology, influenza A virus avian enzymology, orthomyxoviridae enzymology, RNA nucleotidyltransferases metabolism, RNA replicase metabolism, adamantane analogs and derivatives, avian growth and development, orthomyxoviridae growth and development, virus replication drug effects.

Kaluza, G. (1976). Early synthesis of Semliki Forest virus-specific proteins in infected chicken cells. Journal of Virology 19(1): 1-12.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Cells preinfected with fowl plague virus followed by treatment with actinomycin D are a suitable system for studying early protein synthesis in cells infected with Semliki forest virus. One and one-half hours after superinfection, three new nonstructural proteins (NVP) were detected: NVP 145, NVP, 112, and NVP 65. They appeared in parallel with a low incorporation of mannose at the beginning of the infectious cycle. Behavior on chasing suggested a precursor relationship of NVP 112 to the envelope glycoproteins. Two kinds of NVP 65 are described, both of which are varieties of NVP 68 with an incomplete mannose content. One type, detected early after infection, was converted into NVP 68 by supplementary glycosylation. The second, late type was stable. It contains fucose and resembles the NVP 65 observed after impairment of glycosylation. The mechanism of NVP 68 glycosylation is discussed. The presence of the complete carbohydrate moiety is crucial for the cleavage of NVP 68 into the envelope proteins E2 and E3 and, thus, for virus maturation. Only the complete form of NVP 68 was precipitated by envelope-specific antisera. A large production of NVP 78 is a further feature of the early events in infected cells. It is not related to the structural proteins.

            Descriptors:  Semliki Forest virus metabolism, viral proteins biosynthesis, chick embryo, dactinomycin pharmacology, epitopes, glycoproteins biosynthesis, glycoproteins immunology, influenza A virus avian growth and development, mannose metabolism, molecular weight, peptide synthesis, protein precursors biosynthesis, Semliki Forest virus immunology, tissue culture, viral proteins immunology.

Kaluza, G., A.A. Kraus, and R. Rott (1975). Inhibition of cellular protein synthesis by simultaneous pretreatment of host cells with fowl plague virus and actinomycin D: a method for studying early protein synthesis of several RNA viruses. Journal of Virology 17(1): 1-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  A method is described for analysis of viral protein synthesis early after infection when minute amounts of viral proteins are effectively concealed by large amounts of produced host-specific proteins. The method is superior to a radioimmune assay, since all virus-induced proteins can be measured independent of their immunological reactivity. Host-specific protein synthesis can be suppressed by infection with fowl plague virus. Addition of actinomycin C 1.25 h postinfection does not prevent this suppression, but it does block effectively the formation of fowl plague virus-specific proteins. Such cells synthesize only small amounts of cellular proteins, as revealed by polyacrylamide electrophoresis. They can be superinfected with several different enveloped viruses, however, without significant diminution of virus yeilds. In pretreated cells the eclipse is shortened for Semliki Forest virus, Sindbis virus, and vesicular stomatitis virus, but prolonged for Newcastle disease virus. The onset of protein synthesis, specific for the superinfecting virus, could be clearly demonstrated within 1 h after superinfection. At this time, in cells superinfected with Semliki Forest virus, great amounts of NSP 75 (nonstructural protein; molecular weight, 75 X 10(3)) and reduced amounts of the core protein C could be deomonstrated. The precursor glycoprotein NSP 68 is followed by a new polypeptide, NSP 65: three proteins with molecular weights exceeding 100 X 10(3) were observed which are missing later in the infectious cycle. Similar results were obtained after superinfection with Sindbis virus. The formation of a new polypeptide with a molecular weight of about 80 X 10(3) was detected. After superinfection with vesicular stomatis virus or Newcastle disease virus the formation of new proteins, characteristic for the early stage of infeciton, was not observed.

            Descriptors:  dactinomycin pharmacology, influenza A virus avian growth and development, proteins metabolism, RNA viruses metabolism, viral proteins biosynthesis, cell line, glycoproteins biosynthesis, molecular weight, Newcastle disease virus growth and development, Newcastle disease virus metabolism, peptide synthesis, protein precursors biosynthesis, Semliki Forest virus growth and development, Semliki Forest virus metabolism, sindbis virus growth and development, sindbis virus metabolism, tissue culture, vesicular stomatitis Indiana virus growth and development, vesicular stomatitis Indiana virus metabolism, virus replication drug effects.

Kaluza, G., C. Scholtissek, and R. Rott (1972). Inhibition of the multiplication of enveloped RNA-viruses by glucosamine and 2-deoxy-D-glucose. Journal of General Virology 14(3): 251-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  glucosamine pharmacology, hexoses pharmacology, RNA viruses growth and development, virus inhibitors pharmacology, virus replication drug effects, agglutination tests, antigens, viral analysis, cell line, cultured cells microbiology, concanavalin a pharmacology, fluorescent antibody technique, HeLa cells, hemagglutinins viral analysis, influenza A virus avian drug effects, Newcastle disease virus drug effects, polioviruses drug effects, RNA nucleotidyltransferases biosynthesis, RNA viruses drug effects, RNA viruses enzymology, RNA viruses immunology, RNA viruses metabolism, RNA viral biosynthesis, Semliki Forest virus drug effects, sindbis virus drug effects, viral proteins biosynthesis.

Kanegae, Y., S. Sugita, K.F. Shortridge, Y. Yoshioka, and K. Nerome (1994). Origin and evolutionary pathways of the H1 hemagglutinin gene of avian, swine and human influenza viruses: cocirculation of two distinct lineages of swine virus. Archives of Virology 134(1-2): 17-28.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The nucleotide sequences of the HA1 domain of the H1 hemagglutinin genes of A/duck/Hong Kong/36/76, A/duck/Hong Kong/196/77, A/sw/North Ireland/38, A/sw/Cambridge/39 and A/Yamagata/120/86 viruses were determined, and their evolutionary relationships were compared with those of previously sequenced hemagglutinin (H1) genes from avian, swine and human influenza viruses. A pairwise comparison of the nucleotide sequences revealed that the genes can be segregated into three groups, the avian, swine and human virus groups. With the exception of two swine strains isolated in the 1930s, a high degree of nucleotide sequence homology exists within the group. Two phylogenetic trees constructed from the substitutions at the synonymous site and the third codon position showed that the H1 hemagglutinin genes can be divided into three host-specific lineages. Examination of 21 hemagglutinin genes from the human and swine viruses revealed that two distinct lineages are present in the swine population. The swine strains, sw/North Ireland/38 and sw/Cambridge/39, are clearly on the human lineage, suggesting that they originate from a human A/WSN/33-like variant. However, the classic swine strain, sw/Iowa/15/30, and the contemporary human viruses are not direct descendants of the 1918 human pandemic strain, but did diverge from a common ancestral virus around 1905. Furthermore, previous to this the above mammalian viruses diverged from the lineage containing the avian viruses at about 1880.

            Descriptors:  evolution, hemagglutinins viral genetics, influenza A virus avian genetics, human genetics, porcine genetics, amino acid sequence, chick embryo, genes viral, hemagglutinin glycoproteins, influenza virus, avian classification, human classification, porcine classification, molecular sequence data, phylogeny, sequence homology, amino acid.

Kantorovich, E.N., N.V. Kaverin, O.N. Berezina, S.A. Moisiadi, and T.A. Bektemirov (1973). Izuchenie autointerferiruiushchikh svoistv populiatsii virusa grippa, soderzhashchei defktnye virusnye chastitsy. [The autointerfering properties of a population of influenza viruses containing defective virus particles]. Voprosy Virusologii 18(5): 548-52.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  defective viruses, influenza A virus avian, orthomyxoviridae, viral interference, chick embryo, cytopathogenic effect, viral, fetal membranes, fibroblasts, tissue culture, virus cultivation.

Karako, N.I., E.I. Boreko, V.A. Kirillov, and V.I. Votiakov (1989). Izmenenie virusa grippa pri razmnozhenii v prisutstvii vysokikh kontsentratsii remantadine. [Change in the influenza virus upon multiplication in the presence of high concentrations of remantadine]. Voprosy Virusologii 34(1): 43-6.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  It was established that classical fowl plague virus Rostock (H7N1) propagated in culture to which 10-25 micrograms/ml of remantadine had been added differed from the original FPV and its remantadine-resistant variant by markedly reduced infectious and hemagglutinating activity and, to a lesser extent, neuraminidase activity, lower amounts of M protein and hemagglutinin, incomplete cleavage of hemagglutinin, and significant loss of spikes on the virion surface.

            Descriptors:  adamantane analogs and derivatives, influenza A virus avian drug effects, rimantadine pharmacology, drug resistance, microbial, electrophoresis, polyacrylamide gel, hemagglutination, viral drug effects, hemagglutinins viral analysis, influenza A virus avian physiology, influenza A virus avian ultrastructure, viral matrix proteins analysis, viral proteins analysis, virus replication drug effects.

Karasin, A.I., M.M. Schutten, L.A. Cooper, C.B. Smith, K. Subbarao, G.A. Anderson, S. Carman, and C.W. Olsen (2000). Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977-1999: evidence for wholly human and reassortant virus genotypes. Virus Research 68(1): 71-85.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Since 1998, H3N2 viruses have caused epizootics of respiratory disease in pigs throughout the major swine production regions of the U.S. These outbreaks are remarkable because swine influenza in North America had previously been caused almost exclusively by H1N1 viruses. We sequenced the full-length protein coding regions of all eight RNA segments from four H3N2 viruses that we isolated from pigs in the Midwestern U.S. between March 1998 and March 1999, as well as from H3N2 viruses recovered from a piglet in Canada in January 1997 and from a pig in Colorado in 1977. Phylogenetic analyses demonstrated that the 1977 Colorado and 1997 Ontario isolates are wholly human influenza viruses. However, the viruses isolated since 1998 from pigs in the Midwestern U.S. are reassortant viruses containing hemagglutinin, neuraminidase and PB1 polymerase genes from human influenza viruses, matrix, non-structural and nucleoprotein genes from classical swine viruses, and PA and PB2 polymerase genes from avian viruses. The HA proteins of the Midwestern reassortant swine viruses can be differentiated from those of the 1995 lineage of human H3 viruses by 12 amino acid mutations in HA1. In contrast, the Sw/ONT/97 virus, which did not spread from pig-to-pig, lacks 11 of these changes.

            Descriptors:  influenza A virus avian genetics, human genetics, porcine classification, porcine genetics, reassortant viruses genetics, genotype, influenza veterinary, influenza virology, molecular sequence data, North America, phylogeny, swine, swine diseases virology.

Karelin, V., P.N. Kosiakov, and I.u.P. Gofman (1970). Antigeny kletok khoziaina v ochishchennykh suspenziiakh virusa klassicheskoi chumy ptits. [Host cell antigens in purified suspensions of classical fowl plague virus]. Voprosy Virusologii 15(4): 399-404.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  antigens analysis, influenza A virus avian immunology, centrifugation, density gradient, chick embryo, chromatography, complement fixation tests, avian isolation and purification, microscopy, electron, virus cultivation.

Kato, N. and H.J. Eggers (1969). Inhibition of uncoating of fowl plague virus by l-adamantanamine hydrochloride. Virology 37(4): 632-41.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  amantadine pharmacology, influenza A virus avian drug effects, virus replication drug effects, amantadine toxicity, chick embryo, cytopathogenic effect, viral, light, tissue culture.

Katz, J.M., J. Plowden, M. Renshaw Hoelscher, X. Lu, T.M. Tumpey, and S. Sambhara (2004). Immunity to influenza: the challenges of protecting an aging population. Immunologic Research 29(1-3): 113-24.  ISSN: 0257-277X.

            NAL Call Number:  QR180.S88

            Abstract:  Influenza viruses cause annual epidemics and occasional pandemics of acute respiratory disease. Improved vaccines that can overcome the decline in immune function with aging and/or can induce broader immunity to novel pandemic strains are a high priority. To design improved vaccines for the elderly, we need to better understand the effects of age on both innate and adaptive immunity. In a murine model, we have determined that defects in antigen-presenting cell (APC) expression of pattern-recognition molecules, co-stimulatory molecules, and cytokine production may play an important role in the reduced clonal expansion of T cells in aging. The use of immunomodulators such as adjuvants may overcome some of the defects of aging immunity and may also be useful in the development of improved vaccines for avian influenza A subtypes that pose a pandemic threat. Several novel strategies including the use of ISCOM-formulated vaccines, mucosal delivery, or DNA vaccination provided cross-subtype protection that could provide an important component of immunity in the event of a pandemic.

            Descriptors:  aging immunology, disease outbreaks prevention and control, influenza prevention and control, influenza vaccines immunology, adjuvants, immunologic pharmacology, aged, immunity, active immunology, immunity, natural, influenza epidemiology, influenza immunology, influenza A virus, avian immunology, avian pathogenicity, membrane glycoproteins genetics, membrane glycoproteins metabolism, mice, orthomyxoviridae immunology, orthomyxoviridae pathogenicity, receptors, cell surface genetics, receptors, cell surface metabolism.

Kaverin, N.V. and H.D. Klenk (1999). Strain-specific differences in the effect of influenza A virus neuraminidase on vector-expressed hemagglutinin. Archives of Virology 144(4): 781-6.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  In order to evaluate the efficiency of the removal of sialic acid residues from the influenza virus hemagglutinin by the viral neuraminidase in the course of the virus replication cycle, CV-1 cells expressing the hemagglutinin of H7 subtype from an SV40-based vector were superinfected with influenza virus strain A/Duck/Ukraine/63 (H3N8) or A/USSR/90/77 (H1N1). Vector-expressed hemagglutinin was immunoprecipitated from cell lysates and analyzed by polyacrylamide gel electrophoresis. The data indicate that the removal of sialic acid residues from the vector-expressed H7 hemagglutinin by N1 neuraminidase of A/USSR/90/77 virus in the course of the virus replication cycle is incomplete. The results are discussed in connection with previously published data showing that the low activity of NA in wild-type influenza virus results in incomplete removal of sialic acid residues from virion components.

            Descriptors:  hn protein genetics, influenza A virus avian physiology, neuraminidase metabolism, virus replication, cell line, Cecopithecus aethiops, ducks, genetic vectors, hn protein biosynthesis, avian enzymology, avian genetics, simian virus 40, species specificity.

Kaverin, N.V., M. Ohuchi, R. Ohuchi, and H.D. Klenk (1996). Phenotypic mixing with recombinant haemagglutinin of high cleavability mediates multi-cycle replication of human influenza virus in cell culture. Journal of General Virology 77(Pt. 1): 119-22.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  When CV-1 cells expressing haemagglutinin (HA) of fowl plague virus A/FPV/34/Rostock(H7) (FPV) from an SV40-based recombinant vector were superinfected with the human influenza virus A/FM/1/47(H1N1)(FM1), phenotypically mixed progeny virus was observed. It contained cleaved FPV HA and uncleaved FM1 HA, was infectious without trypsin treatment and its infectivity was neutralizable by anti-FPV serum. When superinfection of H7 HA-expressing CV-1 cells was performed at a low multiplicity of infection, multi-cycle replication occurred. Control cells preinfected with an SV40-based recombinant not expressing FPV HA did not allow multi-cycle replication. Multi-cycle replication of FM1 virus was also observed when cells were preinfected with a vector expressing a highly cleavable mutant of influenza virus A/Port Chalmers/1/73(H3) HA carrying an insert of four arginine residues at the cleavage site. This was not the case when cells expressing uncleaved wild-type H3 HA were used. The results show that by phenotypic mixing with recombinant HA of high cleavability, a human influenza virus can be obtained in infectious form from cells lacking a suitable protease to activate this virus.

            Descriptors:  hemagglutinins viral physiology, influenza A virus avian physiology, human physiology, reassortant viruses physiology, cell line, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, avian genetics, human genetics, phenotype, reassortant viruses genetics, trypsin, virus replication.

Kaverin, N.V., I.A. Rudneva, N.A. Ilyushina, N.L. Varich, A.S. Lipatov, Y.A. Smirnov, E.A. Govorkova, A.K. Gitelman, D.K. Lvov, and R.G. Webster (2002). Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza virus and phenotypic variation of escape mutants. Journal of General Virology 83(Pt. 10): 2497-505.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  To elucidate the structure of the antigenic sites of avian H5 influenza virus haemagglutinin (HA) we analysed escape mutants of a mouse-adapted variant of the H5N2 strain A/Mallard/Pennsylvania/10218/84. A panel of five anti-H5 monoclonal antibodies (mAbs) was used to select 16 escape mutants. The mutants were tested by ELISA and haemagglutination inhibition with this panel of anti-H5 mAbs and the HA genes of the mutants were sequenced. The sequencing demonstrated that the amino acid changes were grouped in two antigenic sites. One corresponded to site A in the H3 HA. The other contained areas that are separated in the amino acid sequence but are topographically close in the three-dimensional structure and partially overlap in the reactions with mAbs. This site corresponds in part to site B in the H3 structure; it also includes a region not involved in site B that partially overlaps site Sa in the H1 HA and an antigenic area in H2 HA. Mutants with the amino acid change K152N, as well as those with the change D126N, showed reduced lethality in mice. The substitution D126N, creating a new glycosylation site, was accompanied by an increase in the sensitivity of the mutants to normal mouse serum inhibitors. Several amino acid changes in the H5 escape mutants occurred at the positions of reported changes in H2 drift variants. This coincidence suggests that the antigenic sites described and analysed here may be important for drift variation if H5 influenza virus ever appears as a pathogen circulating in humans.

            Descriptors:  antigenic variation genetics, antigens, viral genetics, epitopes, B lymphocyte genetics, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, antigens, viral chemistry, antigens, viral immunology, base sequence, binding sites, birds, DNA, viral, enzyme linked immunosorbent assay methods, epitope mapping, epitopes, B lymphocyte chemistry, epitopes, B lymphocyte immunology, hemagglutination inhibition tests, hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus immunology, avian immunology, avian pathogenicity, mice, molecular sequence data, mutagenesis, phenotype, protein structure, tertiary, sequence analysis, DNA, virulence.

Kaverin, N.V., I.A. Rudneva, Y.A. Smirnov, and N.N. Finskaya (1988). Human-avian influenza virus reassortants: effect of reassortment pattern on multi-cycle reproduction in MDCK cells. Archives of Virology 103(1-2): 117-26.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Human-avian influenza reassortants possessing the HA gene of the avian parent virus were tested for their ability to replicate in MDCK cells at 37 degrees C and 31 degrees C. Both avian parent viruses, A/Duck/Ukraine/1/63 (H3N8) and A/Duck/Hoshimin/014/78 (H5N3) induced an efficient multi-cycle infection at 37 degrees C, but replicated poorly at 31 degrees C, whereas the human parent virus, MDCK-adapted variant of A/USSR/90/77 (H1N1) strain, replicated efficiently at both temperatures. The reassortant clone possessing the HA gene of A/Duck/Ukraine/1/63 virus and the other 7 genes of A/USSR/90/77 virus replicated at both temperatures almost as efficiently as the human parent virus. Among the reassortants between A/Duck/Hoshimin/014/78 and A/USSR/90/77, the clones possessing the HA and NA genes of the avian strain, or the HA, NA, NP, and NS genes of the avian strain, and the other genes of the human parent virus, replicated poorly at both temperatures, especially at 31 degrees C, whereas the reassortant possessing the HA, NA, and M genes of the avian virus replicated at both temperatures fairly efficiently. The results are discussed in connection with the limitations imposed by different genes upon avian influenza viruses' ability to replicate in mammalian cells.

            Descriptors:  genes viral, hemagglutinins viral physiology, influenza A virus avian pathogenicity, human pathogenicity, virus replication, birds microbiology, chick embryo, hemagglutinins viral biosynthesis, hemagglutinins viral genetics, avian genetics, human genetics, RNA viral analysis, temperature, transfection, viral proteins biosynthesis.

Kaverin, N.V., Y.A. Smirnov, E.A. Govorkova, I.A. Rudneva, A.K. Gitelman, A.S. Lipatov, N.L. Varich, S.S. Yamnikova, N.V. Makarova, R.G. Webster, and D.K. Lvov (2000). Cross-protection and reassortment studies with avian H2 influenza viruses. Archives of Virology 145(6): 1059-66.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  In order to assess the degree of immune cross-protection among avian H2 influenza virus strains, mice were immunised with beta-propiolactone-inactivated virus preparations and infected intranasally with mouse-adapted variant of A/Black Duck/New Jersey/1580/78 (H2N3) strain. The experiments with 11 avian H2 strains revealed that both Eurasian and American H2 avian influenza viruses exhibit either high or moderate degree of cross-protection. The grouping of the strains in accordance with their cross-protection efficiency does not coincide with H2 phylogenetic branches. Several reassortant clones were obtained with the use of A/Pintail Duck/Primorie/695/76 (H2N3) strain and high-yield X-67 reassortant as parent viruses, among them a high-yield H2N3 reassortant. Taking into account the data on cross-protection among avian H2 strains, the high-yield H2N3 reassortant may be regarded as a prototype strain to be used for the preparation of killed vaccines in the case of a new appearance of avian H2 haemagglutinin in circulation in humans.

            Descriptors:  influenza prevention and control, influenza A virus avian genetics, avian immunology, influenza vaccine immunology, reassortant viruses immunology, chick embryo, cross reactions, immunization, influenza immunology, avian pathogenicity, mice, reassortant viruses genetics, vaccines, attenuated immunology.

Kawakami, K., A. Ishihama, and M. Hamaguchi (1981). RNA polymerase of influenza virus. I. Comparison of the virion-associated RNA polymerase activity of various strains of influenza virus. Journal of Biochemistry 89(6): 1751-7.  ISSN: 0021-924X.

            NAL Call Number:  385 J822

            Abstract:  A systematic and comparative study was performed on the polypeptide composition and the RNA polymerase activity associated with virions of various strains of influenza A virus, including four human and two avian viruses. Significant differences were found in the molecular weights of not only hemagglutinin (HA) but also both nucleoprotein (NP) and membrane protein (M), as determined by polyacrylamide gel electrophoresis under denaturing conditions. The results indicate that, among viruses sharing the same serotype determined by the surface proteins HA and NA (neuraminidase), considerable variations exist in the structure of viral proteins, including inner proteins. The relative contents of viral proteins also varied among these strains grown under similar conditions. The total content of three P proteins, the putative RNA polymerase subunits, was within the range between 1.1 and 2.2% of total viral proteins and roughly paralleled the virion-associated RNA polymerase activity. The virion-associated RNA polymerase of all the strains tested were stimulated by the same dinucleotide primers, ApG or GpG, indicating that the specificity of transcription initiation is conserved among wide varieties of influenza virus.

            Descriptors:  DNA directed RNA polymerases metabolism, dinucleoside phosphates, influenza A virus avian enzymology, human enzymology, 5' guanylic acid analogs and derivatives, 5' guanylic acid pharmacology, adenosine monophosphate analogs and derivatives, adenosine monophosphate pharmacology, chemistry, guanosine analogs and derivatives, guanosine pharmacology, macromolecular systems, molecular weight, peptides, species specificity, virion enzymology.

Kawano, J., R. Yanagawa, and H. Kida (1979). Site of replication of influenza virus A/budgerigar/Hokkaido/1/77 (Hav 4 Nav 1) in budgerigars. Zentralblatt Fur Bakteriologie, Parasitenkunde, Infektionskrankheiten Und Hygiene. Erste Abteilung Originale. Reihe A Medizinische Mikrobiologie Und Parasitologie 245(1-2): 1-7.  ISSN: 0300-9688.

            NAL Call Number:  448.3 C33 (1)

            Descriptors:  influenza A virus avian growth and development, parrots microbiology, Psittacines microbiology, virus replication, hemagglutination inhibition tests, avian isolation and purification, organ specificity, respiratory system microbiology.

Kawaoka, Y. (1991). Difference in replication and pathogenicity of influenza A viruses in chickens and mice. Journal of Veterinary Medical Science the Japanese Society of Veterinary Science 53(1): 125-6.  ISSN: 0916-7250.

            NAL Call Number:  SF604.J342

            Descriptors:  chickens microbiology, influenza A virus avian physiology, porcine physiology, influenza A virus physiology, mice microbiology, cloaca microbiology, avian pathogenicity, porcine pathogenicity, influenza A virus pathogenicity, orthomyxoviridae infections microbiology, orthomyxoviridae infections veterinary, poultry diseases microbiology, rodent diseases microbiology, trachea microbiology, virus replication.

Kawaoka, Y. (1991). Structural features influencing hemagglutinin cleavability in a human influenza A virus. Journal of Virology 65(3): 1195-201.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The cleavability of the hemagglutinin (HA) molecule is related to the virulence of avian influenza A viruses, but its influence on human influenza virus strains is unknown. Two structural features are involved in the cleavage of avian influenza A virus HAs: a series of basic amino acids at the cleavage site and an oligosaccharide side chain in the near vicinity. The importance of these properties in the cleavability of a human influenza A virus (A/Aichi/2/68) HA was investigated by using mutants that contained or lacked an oligosaccharide side chain and had either four or six basic amino acids. All mutants except the one that contains a single mutation at the glycosylation site were cleaved, although not completely, demonstrating that a series of basic amino acids confers susceptibility to cellular cleavage enzymes among human influenza virus HAs. The mutants containing six basic amino acids at the cleavage site showed limited polykaryon formation upon exposure to low pH, indicating that cleavage was adequate to impart fusion activity to the HA. Deletion of the potential glycosylation site had no effect on the cleavability of these mutants; hence, the oligosaccharide side chain appears to have no role in human influenza virus HA cleavage. The inability to induce high cleavability in a human influenza A virus HA by insertion of a series of basic amino acids at the cleavage site indicates that other, as yet unidentified structural features are needed to enhance the susceptibility of these HAs to cellular proteases.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus human genetics, amino acid sequence, arginine, cell line, chick embryo, cloning, molecular, glycosylation, hemagglutinin glycoproteins, influenza virus, hydrolysis, human immunology, human ultrastructure, lysine, molecular sequence data,  mutagenesis, site directed, recombination, genetic, simian virus 40 genetics, simian virus 40 ultrastructure, transfection, viral envelope proteins genetics.

Kawaoka, Y., C.W. Naeve, and R.G. Webster (1984). Is virulence of H5N2 influenza viruses in chickens associated with loss of carbohydrate from the hemagglutinin? Virology 139(2): 303-16.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The A/Chick/Penn/83 (H5N2) influenza virus that appeared in chickens in Pennsylvania in April 1983 and subsequently became virulent in October 1983, was examined for plaque-forming ability and cleavability of the hemagglutinin (HA) molecule. The avirulent virus produced plaques and cleaved the HA only in the presence of trypsin. In contrast, the virulent virus produced plaques and cleaved the HA precursor into HA1 and HA2 in the presence or absence of trypsin. The apparent molecular weight of the HA1 from the avirulent virus was higher than that from the virulent virus, but when the viruses were grown in the presence of tunicamycin, the molecular weights of HA were indistinguishable. Two of nine monoclonal antibodies to the HA of the avirulent virus indicate that there is at least one epitope on the HA that is different between the virulent and avirulent viruses. The amino acid sequences of the HAs from the two viruses were compared by sequencing their respective HA gene. The nucleotide sequence coding for the processed HA polypeptide contained 1641 nucleotides specifying a protein of 547 amino acids. The amino acid sequences of the virulent and avirulent viruses were indistinguishable through the connecting peptide region, indicating that the difference in cleavability of the H5 HA is not directly attributed to the amino acid sequence of the connecting peptide. Four of seven nucleotide changes resulted in amino acid changes at residues 13, 69, and 123 of HA1 and at residue 501 of the HA2 polypeptide. Since there were no deletions or insertions in the amino acid sequence of the virulent or avirulent viruses, the possibility exists that the difference in molecular weight is due to loss of a carbohydrate side chain in the virulent strain. The amino acid change in the virulent strain at residue 13 is the only mutation that could affect a glycosylation site and this is in the vicinity of the connecting peptide. It is postulated that the loss of this carbohydrate may permit access of an enzyme that recognizes the basic amino acid sequences and results in cleavage activation of the HA in the virulent virus.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian pathogenicity, amino acid sequence, antibodies, monoclonal, base sequence,  carbohydrates analysis, chick embryo, chickens, DNA, viral genetics, hemagglutinins viral isolation and purification, avian genetics, plaque assay, RNA viral isolation and purification, serotyping, species specificity, virulence.

Kawaoka, Y., A. Nestorowicz, D.J. Alexander, and R.G. Webster (1987). Molecular analyses of the hemagglutinin genes of H5 influenza viruses: origin of a virulent turkey strain. Virology 158(1): 218-27.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Comparative sequence analysis of the hemagglutinin (HA) genes of a highly virulent H5N8 virus isolated from turkeys in Ireland in 1983 and a virus of the same subtype detected simultaneously in healthy ducks showed only four amino acid differences between these strains. Partial sequencing of six of the other genes and antigenic similarity of the neuraminidases established the overall genetic similarity of these two viruses. Comparison of the complete sequence of two H5 gene sequences and partial sequences of other virulent and avirulent H5 viruses provides evidence for at least two different lineages of H5 influenza virus in the world, one in Europe and the other in North America, with virulent and avirulent members in each group. In vivo studies in domestic ducks showed that all of the H5 viruses that are virulent in chickens and turkeys replicate in the internal organs of ducks but did not produce any disease signs. Additionally, both viruses isolated from turkeys and ducks in Ireland were detected in the blood. These studies provide the first conclusive evidence for the possibility that fully virulent influenza viruses in domestic poultry can arise directly from viruses in wild aquatic birds. Studies on the cleavability of the HA of virulent and avirulent H5 viruses showed that the principles established for H7 viruses (F. X. Bosch, M. Orlich, H. D. Klenk, and R. Rott, 1979, Virology 95, 197-207; F. X. Bosch, W. Garten, H. D. Klenk, and R. Rott, 1981, Virology 113, 725-735) also apply to the H5 subtype. These are (1) only the HAs of virulent influenza viruses were cleaved in tissue culture in the absence of trypsin and (2) virulent H5 influenza viruses contain a series of basic amino acids at the cleavage site of the HA, whereas avirulent strains contain only a single arginine with the exception of the avirulent Chicken/Pennsylvania virus. Thus, a series of basic amino acids at the cleavage site probably forms a recognition site for the enzyme(s) responsible for cleavage.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, amino acid sequence, base sequence, chickens microbiology, ducks microbiology, fowl plague microbiology, avian pathogenicity, avian physiology, turkeys microbiology, virulence, virus replication.

Kawaoka, Y. and R.G. Webster (1985). Evolution of the A/Chicken/Pennsylvania/83 (H5N2) influenza virus. Virology 146(1): 130-7.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The epidemiological features of the H5N2 outbreak of influenza in poultry were studied by sequencing the HA genes of several viruses isolated during the epidemic. Comparison of the nucleotide sequences of the HA genes indicated there was a single introduction of virulent virus. The variation rate (silent mutations) in the HA gene of the virulent Ck/Penn virus was 9.0 or 14.4% per 10 years depending on the viruses compared and was similar to that in H3 HA gene of human influenza A virus. The virulent and avirulent viruses isolated after October 1983 were derived from a common ancestoral virus and the virulent virus did not supersede the avirulent virus, instead, the virulent and avirulent viruses coexisted and evolved separately during the course of the epidemic. The evolutionary changes in the HA of H5N2 viruses that occurred during the epidemic permitted us to establish that a virus (A/Chick/Washington/84) that was isolated 8 months after the last H5N2 virus had been isolated from poultry in Pennsylvania belonged to the family of potentially dangerous H5N2 viruses and was a direct descendent of the virus that spread to Maryland and Virginia. All of the virulent Ck/Penn viruses retained the amino acid changes at residues 13 and 69 in the HA.

            Descriptors:  fowl plague microbiology, hemagglutinins viral genetics, influenza A virus avian genetics, amino acid sequence, base sequence,  disease outbreaks veterinary, District of Columbia, evolution, fowl plague epidemiology, genes viral, hemagglutinins viral analysis, avian isolation and purification, avian pathogenicity, Maryland, mutation, Pennsylvania, poultry, virulence.

Kawaoka, Y. and R.G. Webster (1989). Interplay between carbohydrate in the stalk and the length of the connecting peptide determines the cleavability of influenza virus hemagglutinin. Journal of Virology 63(8): 3296-300.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The ability of many viruses to replicate in host cells depends on cleavage of certain viral glycoproteins, including hemagglutinin (HA). By generating site-specific mutant HAs of two highly virulent influenza viruses, we established that the relationship between carbohydrate in the stalk and the length of the connecting peptide is a critical determinant of cleavability. HAs that lacked an oligosaccharide side chain in the stalk were cleaved regardless of the number of basic amino acids at the cleavage site, whereas those with the oligosaccharide side chain resisted cleavage unless additional basic amino acids were inserted. This finding suggests that the oligosaccharide side chain interferes with HA cleavage if the number of basic amino acids at the cleavage site is not adequate to nullify this effect. Similar interplay could influence cleavage of other viral glycoproteins, such as those of human and simian immunodeficiency viruses and paramyxoviruses.

            Descriptors:  carbohydrates metabolism, hemagglutinins viral metabolism, influenza A virus avian metabolism, oligosaccharides metabolism, amino acid sequence, amino acids, glycosylation, hemagglutinins viral genetics, avian genetics, molecular sequence data, mutation.

Kawaoka, Y. and R.G. Webster (1988). Molecular mechanism of acquisition of virulence in influenza virus in nature. Microbial Pathogenesis 5(5): 311-8.  ISSN: 0882-4010.

            NAL Call Number:  QR175.M53

            Descriptors:  influenza A virus avian pathogenicity, chickens, influenza epidemiology, influenza microbiology, avian genetics, orthomyxoviridae pathogenicity, virulence.

Kawaoka, Y. and R.G. Webster (1988). Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America 85(2): 324-8.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Cleavage of the hemagglutinin (HA) in tissue culture systems has been correlated with virulence of avian influenza viruses. To examine the structural requirements for cleavage of the HA, the HA gene from a virulent H5 influenza virus was expressed in mammalian cells (CV-1), and the cleavage site of the HA was explored by using site-specific mutagenesis. The expressed HA protein exhibited normal cleavage, transport to the cell membrane, and ability to adsorb and to fuse erythrocytes at pH 5. Site-specific mutagenesis of the HA directly established that (i) most of the basic amino acids at this site are critical for cleavage activation; (ii) besides the connecting peptide sequence, at least one other structural feature of the HA is required for enzyme recognition; and (iii) the length of the connecting peptide can abrogate the structural feature(s).

            Descriptors:  hemagglutinins viral genetics, influenza A virus human genetics, amino acid sequence, cell line, cloning, molecular, DNA restriction enzymes, hemadsorption, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, human immunology, human pathogenicity, plasmids, simian virus 40 genetics, species specificity, transfection, virulence.

Keawcharoen, J., K. Oraveerakul, T. Kuiken, R.A. Fouchier, A. Amonsin, S. Payungporn, S. Noppornpanth, S. Wattanodorn, A. Theambooniers, R. Tantilertcharoen, R. Pattanarangsan, N. Arya, P. Ratanakorn, D.M. Osterhaus, and Y. Poovorawan (2004). Avian influenza H5N1 in tigers and leopards. Emerging Infectious Diseases 10(12): 2189-91.  ISSN: 1080-6040.

            NAL Call Number:  RA648.5.E46

            Abstract:  Influenza virus is not known to affect wild felids. We demonstrate that avian influenza A (H5N1) virus caused severe pneumonia in tigers and leopards that fed on infected poultry carcasses. This finding extends the host range of influenza virus and has implications for influenza virus epidemiology and wildlife conservation.

            Descriptors:  zoo animals virology, influenza veterinary, influenza A virus, avian pathogenicity, Panthera virology, chickens virology, food microbiology, influenza virology, avian genetics, lung virology, meat virology, phylogeny, tigers virology, variation genetics.

Keil, W., R. Geyer, J. Dabrowski, U. Dabrowski, H. Niemann, S. Stirm, and H.D. Klenk (1985). Carbohydrates of influenza virus. Structural elucidation of the individual glycans of the FPV hemagglutinin by two-dimensional 1H n.m.r. and methylation analysis. EMBO Journal 4(10): 2711-20.  ISSN: 0261-4189.

            NAL Call Number:  QH506.E46

            Abstract:  The structures of the oligosaccharides of the hemagglutinin of fowl plague virus [influenza A/FPV/Rostock/34 (H7N1)] have been elucidated by one- and two-dimensional 1H n.m.r. spectroscopy at 500 MHz and by microscale methylation analysis. N-Glycosidic oligosaccharides of the oligomannosidic (OM) and of the N-acetyllactosaminic type have been found, the latter type comprising biantennary structures, without (A) or with (E) bisecting N-acetylglucosamine, and triantennary (C) structures. Analysis of the tryptic and thermolytic glycopeptides of the hemagglutinin allowed the allocation of these oligosaccharides to the individual glycosylation sites. Each attachment site contained a unique set of oligosaccharides. Asn12 contains predominantly structures C and E which are highly fucosylated. Asn28 contains OM and A structures that lack fucose and sulfate. Asn123 shows A that has incomplete antennae but is highly fucosylated and sulfated. Asn149 has fucosylated A and E. Asn231 shows fucosylated A and E with incomplete antennae. Asn406 has OM oligosaccharides. Asn478 has A and E with little fucose. Localization of the oligosaccharides on the three-dimensional structure of the hemagglutinin revealed that the oligomannosidic glycans are attached to glycosylation sites at which the enzymes responsible for carbohydrate processing do not have proper access. These observations demonstrate that an important structural determinant for the oligosaccharide side chains is the structure of the glycoprotein itself. In addition, evidence was obtained that the rate of glycoprotein synthesis also has an influence on carbohydrate structure.

            Descriptors:  glycoproteins, hemagglutinins viral, influenza A virus avian, glycopeptides analysis, magnetic resonance spectroscopy, methylation, oligosaccharides analysis, protein processing, post translational.

Keil, W., H.D. Klenk, and R.T. Schwarz (1979). Carbohydrates of influenza virus. III. Nature of oligosaccharide-protein linkage in viral glycoproteins. Journal of Virology 31(1): 253-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Four different glycopeptides can be distinguished after pronase digestion of influenza A virus glycoproteins: Ia and Ib, containing N-acetylglucosamine, mannose, galactose, and fucose, and IIa and IIb, containing mannose and N-acetylglucosamine. All glycopeptides yielded N-acetylglucosaminyl-asparagine after mild acid hydrolysis. There was no evidence for O-glycosidic bonds. Thus, the carbohydrate complement is linked to the polypeptide exclusively by N-glycosidic linkages between N-acetylglucosamine and asparagine.

            Descriptors:  glycoproteins analysis, influenza A virus analysis, viral proteins analysis, acetylglucosamine analysis, asparagine analysis, carbohydrate conformation, glycopeptides analysis, influenza A virus avian analysis, molecular weight, oligosaccharides analysis, protein conformation.

Keil, W., H. Niemann, R.T. Schwarz, and H.D. Klenk (1984). Carbohydrates of influenza virus. V. Oligosaccharides attached to individual glycosylation sites of the hemagglutinin of fowl plague virus. Virology 133(1): 77-91.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The carbohydrate side chains of the hemagglutinin of fowl plague virus (A/FPV/Rostock/34 (H7N1] have been localized by a procedure involving fragmentation of the polypeptide with cyanogen bromide and various proteases. The positions of the fragments were determined by radioactive labeling of the sugars and of specific amino acids. Side chains of the complex type I are attached to asparagine residues 12, 28, 123, 149, and 478. A mannose-rich (type II) side chain is linked to asparagine 406. Asparagine 231 is not glycosylated. The side chains attached to asparagine residues 12, 123, 149, and 478 contain sulfate. Glycopeptides derived by Pronase digestion from the individual attachment sites have been analyzed by their affinity to concanavalin A and Lens culinaris agglutinin. The results indicate that each glycosylation site has a typical set of heterogeneous oligosaccharides. Comparison of the glycosylation patterns of the hemagglutinins of FPV and other influenza A viruses reveals that the glycosylation sites at asparagine residues 12, 28, and 478, which are located at the base of the spike, are highly conserved. Mannose-rich side chains appear to be located preferentially at interfaces between the three monomers of a spike or between the globular and fibrous domains of a monomer.

            Descriptors:  hemagglutinins viral isolation and purification, influenza A virus avian immunology, oligosaccharides analysis, serine endopeptidases, acetylglucosaminidase, amino acid sequence, chromatography, affinity, cyanogen bromide, endopeptidases, glycopeptides analysis, hemagglutinins viral genetics, mannosyl glycoprotein endo beta N-acetylglucosaminidase, pronase,  trypsin.

Kelly, D.C., R.J. Avery, and N.J. Dimmock (1974). Failure of an influenza virus to initiate infection in enucleate BHK cells. Journal of Virology 13(6): 1155-61.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  cell nucleus physiology, orthomyxoviridae growth and development, virus replication, antigens, viral analysis, cell line, electrophoresis, polyacrylamide gel, fluorescent antibody technique, hamsters, influenza A virus avian growth and development, kidney, methionine, Newcastle disease virus growth and development, nucleic acid hybridization, peptides analysis, sulfur radioisotopes, tritium, uridine, vaccinia virus growth and development.

Kelly, D.C. and N.J. Dimmock (1974). Fowl plaque virus replication in mammalian cell-avian erythrocyte heterokaryons: studies concerning the actinomycin D and ultra-violet light sensitive phase in influenza virus replication. Virology 61(1): 210-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cell nucleus microbiology, dactinomycin pharmacology, influenza A virus avian growth and development, ultraviolet rays, virus replication drug effects, virus replication radiation effects, antigens, viral analysis, autoradiography, cell fusion, cell line, cell nucleus immunology, cultured cells cytology, chick embryo, chickens, erythrocytes cytology, fluorescent antibody technique, hamsters, hemagglutinins viral, avian immunology, avian metabolism, kidney, l cells cell line, mice, neuraminidase biosynthesis, nucleoproteins biosynthesis, radiation effects, viral proteins biosynthesis.

Kendal, A.P. and H.D. Klenk (1991). Amantadine inhibits an early, M2 protein-dependent event in the replication cycle of avian influenza (H7) viruses. Archives of Virology 119(3-4): 265-73.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Analysis of the effects of amantadine during a single cycle of replication of A/FPV/Rostock virus in vitro showed that, as with other influenza A viruses, an M2 protein-dependent step early in infection was inhibited. No effect was observed on later steps in replication under the conditions used.

            Descriptors:  amantadine pharmacology, influenza A virus avian drug effects, viral matrix proteins biosynthesis, viral matrix proteins drug effects, viral matrix proteins genetics, base sequence, avian genetics, avian physiology, molecular sequence data, mutation, viral proteins biosynthesis, virus replication drug effects.

Khadzhiev, G. (1974). Vurkhu adsorbtsiiata na khemaglutininite na virusi na psevdochumata na mozuchni kletki in vitro [Absorption of hemagglutinins from the pseudopest virus by brain cells in vitro].  Veterinarnomeditsinski Nauki 11(5): 93-7.  ISSN: 0324-1068.

            NAL Call Number:  41.8 V6468

            Descriptors:  brain metabolism, hemagglutinins viral metabolism, influenza A virus avian immunology, brain cytology, cultured cells, chick embryo, tissue culture metabolism.

Kharitonenko, I.G., I.U.A. Zakomyrdin, A.K. Gitel'man, and A.G. Bukrinskaia (1980). Izuchenie struktury lipidnoi obolochki virionov grippa, vyrashchennykh v raznykh khoziaevakh. [Structural study of the lipid envelope of influenza virions grown in different hosts]. Voprosy Virusologii (6): 708-12.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  influenza A virus avian analysis, lipids analysis, virion analysis, carcinoma, Ehrlich tumor microbiology, chick embryo, electron spin resonance spectroscopy methods, spin labels, virus cultivation.

Kharitonenkov, I.G., V.P. Ginzburg, A.I. Klimov, and A.N. Tikhonov (1982). Vzaimodeistvie remantadina s lipidnoi membranoi chuvstvitel'nykh i rezistentnykh k preparatu variantov virusa grippa. [Interaction of rimantadine with the lipid membrane of influenza virus variants sensitive to the drug]. Voprosy Virusologii 27(5): 52-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  adamantane analogs and derivatives, orthomyxoviridae drug effects, rimantadine pharmacology, drug resistance, microbial, influenza A virus avian drug effects, influenza A virus drug effects, variation genetics.

Khatchikian, D., M. Orlich, and R. Rott (1989). Increased viral pathogenicity after insertion of a 28S ribosomal RNA sequence into the haemagglutinin gene of an influenza virus. Nature  340(6229): 156-7.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Abstract:  The haemagglutinin glycoprotein HA of influenza viruses is responsible for the attachment of the virus to neuraminic acid-containing receptors at the cell surface and subsequent penetration by triggering fusion of the viral envelope with cellular membranes. To express full activity of the newly synthesized precursor, HA has to be modified by post-translational proteolytic cleavage into the polypeptides HA1 and HA2 by cellular enzymes. If proteases suitable for cleavage are not present in the host cell, the resulting virus particles are non-infectious. During adaptation of the apathogenic influenza virus A/turkey/Oregon/71 to chicken embryo cells, which are not permissive for HA cleavage, we obtained an infectious virus variant with increased pathogenicity. Sequence analysis revealed that during adaptation 54 nucleotides were inserted into the HA gene; their sequence corresponds to a region of the 28S ribosomal RNA. This insertion is probably responsible for increased cleavability of HA, as well as for infectivity and pathogenicity of the adapted virus.

            Descriptors:  DNA transposable elements, hemagglutinins viral genetics, influenza A virus avian pathogenicity, RNA, ribosomal genetics, ribosomal, 28S genetics, base sequence, cloning, molecular, hemagglutinin glycoproteins, influenza virus, avian genetics, molecular sequence data, recombinant fusion proteins genetics, turkeys, viral fusion proteins metabolism, virulence.

Kida, H., L.E. Brown, and R.G. Webster (1982). Biological activity of monoclonal antibodies to operationally defined antigenic regions on the hemagglutinin molecule of A/Seal/Massachusetts/1/80 (H7N7) influenza virus. Virology 122(1): 38-47.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, antibodies, monoclonal, antibodies, viral, antibody specificity, antigen antibody reactions, epitopes.

Kida, H., R. Yanagawa, and Y. Matsuoka (1980). Duck influenza lacking evidence of disease signs and immune response. Infection and Immunity 30(2): 547-53.  ISSN: 0019-9567.

            NAL Call Number:  QR1.I57

            Abstract:  Influenza viruses A/duck/Hokkaido/5/77 (Hav7N2), A/budgerigar/Hokkaido/1/77 (Hav4Nav1), A/Kumamoto/22/76 (H3N2), A/Aichi/2/68 (H3N2), and A/New Jersey/8/76 (Hsw1N1) were experimentally inoculated into Pekin ducks. Of these, the influenza viruses of duck and budgerigar origin replicated in the intestinal tract of the ducks. The infected ducks shed the virus in the feces to high titers, but did not show clinical signs of disease and scarcely produced detectable serum antibodies. Using immunofluorescent staining, we demonstrated that the target cells of the duck virus in ducks were the simple columnar epithelial cells which form crypts in the large intestines, especially in the colon. After primary infection, the birds resisted reinfection with the duck virus at least for 28 days, but from 46 days onward they were susceptible to reinfection. These infections were quickly restricted by a brisk secondary immune response, reflected in the rapid appearance of high titers of antibody after reinoculation. In contrat to the avian influenza viruses, the remaining three influenza viruses of human origin did not replicate in the intestinal tract but did cause a serum antibody response.

            Descriptors:  ducks microbiology, influenza veterinary, influenza A virus avian growth and development, antibody formation, digestive system microbiology, feces microbiology, influenza immunology, human growth and development, parakeets microbiology, virus replication.

King, A.P. and K.F. Shortridge (1982). Multiple avain influenza infection: selection of a non-avid virus by a heterologous avain host. Research in Veterinary Science 33(1): 127-9.  ISSN: 0034-5288.

            NAL Call Number:  41.8 R312

            Abstract:  Experimental infection of domestic fowl, ducks and geese with an influenza A virus (H7N2) isolated from a domestic duck showed that this virus was apathogenic for these poultry. A second virus (H6N2), also apathogenic and more 'non-avid' than any such isolates previously recognised in surveillance of domestic poultry in Hong Kong, was isolated from one goose after H7N2 shedding had ceased. This goose, in effect, acted as a selective isolation system for the H6N2 virus whose presence in the field isolate could not be detected in spite of multiple passage in embryonated eggs.

            Descriptors:  chickens microbiology, ducks microbiology, fowl plague microbiology, geese microbiology,  influenza A virus avian pathogenicity, poultry diseases microbiology.

Kishida, N., Y. Sakoda, M. Eto, Y. Sunaga, and H. Kida (2004). Co-infection of Staphylococcus aureus or Haemophilus paragallinarum exacerbates H9N2 influenza A virus infection in chickens. Archives of Virology 149(11): 2095-104.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  H9N2 influenza viruses are frequently isolated from chicken meat and bone marrow imported from China to Japan since 2001. These isolates were experimentally inoculated into specific pathogen-free chickens intranasally. Viruses were recovered from the meat and bone marrow of birds showing no overt signs. On the other hand, chickens co-infected with H9N2 virus and either Staphylococcus aureus or Haemophilus paragallinarum showed clinical signs severer than those shown by birds infected only with the virus alone or each of the bacteria alone. In addition, H9N2 viruses were more efficiently recovered from the chickens co-infected with S. aureus or H. paragallinarum than those from the birds infected with only the virus. The present results indicate that co-infection of H9N2 influenza virus with S. aureus or H. paragallinarum enhances the replication of the virus in chickens, resulting in exacerbation of the H9N2 virus infection.

            Descriptors:  chickens virology, haemophilus infections veterinary, Haemophilus paragallinarum, influenza A virus, avian, influenza, avian virology, poultry diseases virology, staphylococcal infections veterinary, chickens microbiology, haemophilus infections complications, poultry diseases microbiology, specific pathogen free organisms, staphylococcal infections complications, virus replication.

Kistner, O., K. Muller, and C. Scholtissek (1989). Differential phosphorylation of the nucleoprotein of influenza A viruses. Journal of General Virology 70(Pt. 9): 2421-31.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  An analysis of the nucleoprotein (NP) of 29 different influenza A viruses by phosphopeptide fingerprinting revealed three prototype patterns. The first, which was a complex pattern consisting of six to seven phosphopeptides, another which was relatively simple consisted of two or three phosphopeptides, and a third one which was complex but was missing the main phosphopeptide shared by the two other patterns. Phosphoserine was the only labelled phosphamino acid detected. A tentative deduction of two of the phosphate attachment sites (serine residues at positions 3 and 473) could be made by comparison of the known amino acid sequences of the NPs of 25 strains. No correlation was found between species specificity or subtype or year of isolation of the strains. During the infectious cycle the fingerprint underwent significant changes, indicating subtle phosphorylation and dephosphorylation of the NP at various stages during viral multiplication. Most of the phosphopeptides were metabolically stable; however one major phosphopeptide, which was not found in the NP of mature virions, exhibited a high turnover (presumably serine at position 3). The phosphopeptide fingerprint could be significantly influenced in vivo by the specific stimulation of cellular protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate or by its inhibition with the isoquinoline sulphonamide H7.H7 specifically inhibited the replication of influenza A viruses by deregulation of viral protein synthesis without interfering with the multiplication of a parainfluenza virus (Newcastle disease virus), an alphavirus (Semliki Forest virus) or a flavivirus (West Nile). Therefore the correct phosphorylation of the NP of influenza viruses appears to be essential for influenza virus replication.

            Descriptors:  influenza A virus analysis, nucleoproteins isolation and purification, phosphoproteins isolation and purification, 1 5 isoquinolinesulfonyl 2 methylpiperazine, amino acids analysis, chick embryo, influenza A virus avian analysis, influenza A virus avian physiology, influenza A virus human analysis, influenza A virus, porcine analysis,  influenza A virus metabolism, isoquinolines pharmacology, nucleoproteins metabolism, peptide mapping, phosphopeptides isolation and purification, phosphoproteins biosynthesis, phosphorylation, piperazines pharmacology, protein kinase c metabolism, species specificity, tetradecanoylphorbol acetate pharmacology, virus replication.

Kiyotani, K., N. Takei, M. Senoo, S. Takao, K. Otsuki, M. Tsubokura, and T. Yoshida (1987). Enzymological characteristics of avian influenza A virus neuraminidase. Microbiology and Immunology 31(11): 1131-5.  ISSN: 0385-5600.

            NAL Call Number:  448.8 J273

            Abstract:  Neuraminidases of 18 strains of avian influenza A virus were examined by both colorimetric and fluorometric assays using fetuin and 4-methylumbelliferyl-N-Ac-alpha-D-neuraminide as substrates, respectively, to compare them with those of human influenza A and B viruses. The ratios of the neuraminidase activity of avian influenza virus measured by the colorimetric assay method to that measured by the fluorometric assay were distributed in the range of 2.4-20.3. The enzyme of avian influenza virus showed calcium-ion dependence in both assay methods. These results suggest that neuraminidase of avian influenza A virus is varies greatly from one strain to another in substrate specificity as compared with those of human influenza A and B viruses, and that some strains of avian influenza A virus have a neuraminidase with unique enzymological characteristics different from that of human influenza A virus as well as that of influenza B virus.

            Descriptors:  influenza A virus avian enzymology, neuraminidase metabolism, colorimetry, edetic acid pharmacology, epitopes, fluorometry, species specificity, substrate specificity.

Kleineidam, R.G., K. Furuhata, H. Ogura, and R. Schauer (1990). 4-Methylumbelliferyl-alpha-glycosides of partially O-acetylated N-acetylneuraminic acids as substrates of bacterial and viral sialidases. Biological Chemistry Hoppe Seyler 371(8): 715-9.  ISSN: 0177-3593.

            NAL Call Number:  384 Z38

            Abstract:  4-O-Acetylated, 7-O-acetylated, and 9-O-acetylated 4-methylumbelliferyl-alpha-N-acetyl-neuraminic acids (Neu4,5Ac2-MU, Neu5,7Ac2-MU, Neu5,9Ac2-MU) were tested as substrates of sialidases of Vibrio cholerae and of Clostridium perfringens. Both sialidases were unable to hydrolyse Neu4,5Ac2-MU. This compound at 1 mM concentration did not inhibit significantly the cleavage of Neu5Ac-MU, the best substrate tested. The 4-O-acetylated sialic acid glycoside is hydrolysed slowly by the sialidase from fowl plague virus. The relative substrate specificity, reflected in V/Km of the Vibrio cholerae sialidase is Neu5Ac-MU much greater than Neu5,7Ac2-MU approximately Neu5,9Ac2-MU and of the clostridial enzyme it is Neu5Ac-MU greater than Neu5,9Ac2-MU greater than Neu5,7Ac2-MU. The affinities of both enzymes for the side-chain O-acetylated sialic acid derivatives are higher than for Neu5Ac-MU. The artificial, well-defined substrates, described here, provide the opportunity to quantify the influence of sialic acid O-acetylation on the hydrolysis of sialoglycoconjugates without the side effects introduced by other parts of more complex glycans.

            Descriptors:  glycosides metabolism, hymecromone analogs and derivatives, neuraminidase metabolism, sialic acids metabolism, acetylation, Clostridium perfringens enzymology, hymecromone metabolism, influenza A virus avian enzymology, kinetics, species specificity, substrate specificity,  Vibrio cholerae enzymology.

Klenk, H.D. (1983). Biosynthesis of myxovirus glycoproteins with special emphasis on mutants defective in glycoprotein processing. Methods in Enzymology 96: 434-43.  ISSN: 0076-6879.

            NAL Call Number:  QP601.M49

            Descriptors:  glycoproteins genetics, influenza A virus avian genetics, mutation, viral proteins genetics, cell line, cell membrane metabolism, cell transformation, viral, cultured cells, chick embryo, dogs, glycoproteins isolation and purification, hamsters, kidney, Newcastle disease virus genetics, Newcastle disease virus isolation and purification, parainfluenza virus 1, human genetics, parainfluenza virus 1, human isolation and purification, viral proteins isolation and purification.

Klenk, H.D., H. Becht, and R. Rott (1974). Reaction of viruses and virus-infected cells with heterophile agglutinins. Annals of the New York Academy of Sciences 234(0): 355-68.  ISSN: 0077-8923.

            NAL Call Number:  500 N484

            Descriptors:  antigen antibody reactions, antigens, viral, cultured cells immunology, influenza A virus avian immunology, lectins, cell line, chick embryo, concanavalin A, fibroblasts, glycoproteins immunology, hamsters, HeLa cells, hemadsorption, hemadsorption inhibition tests, avian ultrastructure, kidney, l cells cell line, mice, viral proteins biosynthesis, viral proteins immunology, virus replication.

Klenk, H.D., W. Garten, and R. Rott (1984). Inhibition of proteolytic cleavage of the hemagglutinin of influenza virus by the calcium-specific ionophore A23187. EMBO Journal 3(12): 2911-5.  ISSN: 0261-4189.

            NAL Call Number:  QH506.E46

            Abstract:  At calcium-specific ionophore A23187 concentrations of approximately 0.25 microM [which still allow assembly and release of fowl plague virus (FPV) particles] post-translational proteolytic cleavage of the viral hemagglutinin precursor HA into the fragments HA1 and HA2 is inhibited. The resulting virus particles with uncleaved hemagglutinin, that cannot be obtained under normal conditions, provide a suitable substrate for in vitro assays of the protease sensitivity of the FPV hemagglutinin. Proteolytic activation is accomplished with trypsin. Treatment with cathepsin B at low pH yields aberrant cleavage products suggesting that the cellular cleavage enzyme is not of lysosomal origin. A protease that cleaves the FPV hemagglutinin in the correct place can be detected in lysates of MDBK cells. This enzyme is calcium dependent and has a neutral pH optimum.

            Descriptors:  calcimycin pharmacology, influenza A virus avian genetics, thermolysin metabolism, viral envelope proteins analysis, viral matrix proteins, cattle, cell line, hamsters, hemagglutination tests, avian drug effects, kidney, plaque assay, virus replication drug effects.

Klenk, H.D., W. Keil, H. Niemann, R. Geyer, and R.T. Schwarz (1983). The characterization of influenza A viruses by carbohydrate analysis. Current Topics in Microbiology and Immunology 104: 247-57.  ISSN: 0070-217X.

            NAL Call Number:  QR1.C8

            Descriptors:  carbohydrates analysis, hemagglutinins viral analysis, influenza A virus avian analysis, influenza A virus analysis, chemistry, glycopeptides analysis, avian immunology, human analysis, porcine analysis, influenza A virus classification, influenza A virus immunology, serotyping, species specificity.

Klenk, H.D., K. Kuroda, E. Kretzschmar, R. Geyer, A. Groner, and W. Doerfler (1991). Processing of influenza virus hemagglutinin in insect cells. Behring Institute Mitteilungen (89): 27-34.  ISSN: 0301-0457.

            NAL Call Number:  QR180.B4

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, influenza A virus genetics, baculoviridae genetics, carbohydrate conformation, cell line, genetic vectors, hemadsorption, hemagglutinin glycoproteins, influenza virus, avian physiology, influenza A virus physiology, insects, larva, moths, oligosaccharides analysis, viral envelope proteins genetics.

Klenk, H.D. and R. Rott (1973). Formation of influenza virus proteins. Journal of Virology 11(6): 823-31.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Descriptors:  influenza A virus avian metabolism, viral proteins biosynthesis, amino acids metabolism, carbon isotopes, chick embryo, electrophoresis, polyacrylamide gel, fibroblasts, fluorine, glucosamine metabolism, glycoproteins biosynthesis, glycoproteins metabolism, hemagglutination tests, hemagglutinins viral, influenza A virus avian growth and development, isoflurophate pharmacology, peptide synthesis, phenylalanine pharmacology, plaque assay, protein precursors biosynthesis, temperature, tissue culture, tritium,  viral proteins metabolism, virus replication.

Klenk, H.D., R. Rott, and H. Becht (1972). On the structure of the influenza virus envelope. Virology 47(3): 579-91.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  carbohydrates analysis, influenza A virus avian analysis, lipids analysis, viral proteins analysis, agglutination tests, antigens, viral analysis, bromelains, carbon isotopes, centrifugation, density gradient, chick embryo, concanavalin a, electrophoresis, disc, erythrocytes immunology,  fibroblasts, glycoproteins analysis, avian immunology, microscopy, electron, molecular weight, peptides analysis, sucrose, tissue culture, tritium, virus cultivation.

Klenk, H.D., R. Rott, and M. Orlich (1977). Further studies on the activation of influenza virus by proteolytic cleavage of the haemagglutinin. Journal of General Virology 36(1): 151-61.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  glycoproteins metabolism, hemagglutinins viral, influenza A virus avian growth and development, influenza A virus growth and development, viral proteins metabolism, chick embryo, glycosaminoglycans metabolism, avian metabolism, influenza A virus metabolism, peptide hydrolases metabolism, tissue culture, trypsin metabolism, virus replication.

Klenk, H.D., R. Rott, M. Orlich, and J. Blodorn (1975). Activation of influenza A viruses by trypsin treatment. Virology 68(2): 426-39.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  orthomyxoviridae pathogenicity, trypsin pharmacology, adsorption, arteritis virus, equine analysis, arteritis virus, equine growth and development, arteritis virus, equine pathogenicity, chick embryo, fetal membranes, glycoproteins analysis, hemagglutinins viral analysis, influenza A virus avian analysis, avian growth and development, avian pathogenicity, human analysis, human growth and development, human pathogenicity, porcine analysis, porcine growth and development, porcine pathogenicity, peptides analysis, tissue culture, viral proteins analysis, virulence, virus replication.

Klenk, H.D., C. Scholtissek, and R. Rott (1972). Inhibition of glycoprotein biosynthesis of influenza virus by D-glucosamine and 2-deoxy-D-glucose. Virology 49(3): 723-34.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  glucosamine pharmacology, glucose pharmacology, glycoproteins biosynthesis, influenza A virus avian metabolism, viral proteins biosynthesis, amino acids metabolism, carbon isotopes, cultured cells metabolism, cultured cells microbiology, chick embryo, chromatography, electrophoresis, polyacrylamide gel, fibroblasts microbiology, fucose metabolism, galactose metabolism, hemagglutinins viral biosynthesis, avian enzymology, avian growth and development, molecular weight, neuraminidase biosynthesis, peptide synthesis, stereoisomerism, tritium,  uridine metabolism.

Klenk, H.D., W. Wollert, R. Rott, and C. Scholtissek (1974). Association of influenza virus proteins with cytoplasmic fractions. Virology 57(1): 28-41.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cultured cells metabolism, glycoproteins metabolism, influenza A virus avian metabolism, viral proteins metabolism, carbon radioisotopes, cell fractionation, cell line, chick embryo, DNA directed RNA polymerases metabolism, electrophoresis, polyacrylamide gel, fibroblasts, glucosamine pharmacology, glucose pharmacology, glycoproteins analysis, avian analysis, avian enzymology, avian growth and development, microscopy, electron, neuraminidase metabolism, nucleoproteins analysis, peptides analysis, subcellular fractions analysis, subcellular fractions metabolism, tritium,  viral proteins analysis.

Klimov, A., Y. Ghendon, H. Zavadova, J. Broucek, and T. Medvedeva (1983). High reproduction capacity of recombinants between H3N2 human influenza and fowl plague viruses is due to the gene coding for M proteins. Acta Virologica 27(5): 434-8.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Recombinants between H3N2 human influenza viruses (A/Victoria/3/75 and A/Bangkok/1/79, low-yielding parents in chick embryos) and fowl plague virus (FPV, a high-yielding parent in chick embryos) have been obtained. The high reproductive capacity of recombinants in chick embryos has been shown to be due to the gene coding for M proteins.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, recombination, genetic, viral proteins genetics, virus replication, chick embryo, avian physiology, human physiology, viral matrix proteins.

Klimov, A., S. Prosch, J. Schafer, and D. Bucher (1992). Subtype H7 influenza viruses: comparative antigenic and molecular analysis of the HA-, M-, and NS-genes. Archives of Virology 122(1-2): 143-61.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Antigenic analysis of the haemagglutinin and matrix protein with corresponding sets of monoclonal antibodies as well as sequence analysis of HA-, M-, and NS-genes were carried out to establish antigenic and genetic relationships between four fowl plague virus (FPV) strains of H7 subtype. The data obtained revealed close genetic relatedness between the oldest known influenza A virus, A/chicken/Brescia/1902 (H7N7), and two FPV strains, A/FPV/Dobson (H7N7) and A/FPV/Weybridge (H7N7). These three strains apparently differ in all genes investigated from the A/FPV/Rostock isolate.

            Descriptors:  capsid genetics, genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, viral core proteins genetics, viral matrix proteins genetics, amino acid sequence, base sequence, capsid immunology, DNA, viral, deoxyribonucleotides, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, avian immunology, molecular sequence data, sequence homology, nucleic acid, species specificity, viral core proteins immunology, viral matrix proteins immunology, viral nonstructural proteins.

Klimov, A.I. and Y.Z. Ghendon (1975). The effect of the isolation procedure on the transcriptase activity of fowl plaque virus ribonucleoprotein. Acta Virologica 19(1): 91.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  centrifugation, density gradient methods, DNA directed RNA polymerases metabolism, influenza A virus avian enzymology, nucleoproteins isolation and purification, viral proteins isolation and purification, cell free system, deoxycholic acid, mercaptoethanol, sucrose, tritium, uracil nucleotides metabolism, urea.

Klimov, A.I. and Y.Z. Ghendon (1976). Investigation on the biological activity of fowl plague virus ribonucleoprotein. Acta Virologica 20(4): 273-82.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Fowl plague virus (FPV) ribonucleoprotein (RNP) bands in sucrose density gradient in a heterogeneous peak with sedimentation coefficients from 45 to 70 S, whereas in cesium chloride gradient it has a homogeneous density of 1.33-1.34 g/cm3. FPV RNP contains 7.4-8% RNA. Upon inoculation of chick embryo cell cultures. FPV RNP shows no infectivity, does not induce virus-specific protein synthesis and does not participate in complementation or recombination interactions with ts mutants of FPV. The biological activity of FPV RNP demonstrable under certain experimental conditions is due to admixture of undestroyed virions and is completely eliminated by treatment of the preparation with gamma-globulin fraction of antiserum to FPV haemagglutinin, but not with antiserum to RNP proteins.

            Descriptors:  influenza A virus avian analysis, influenza A virus avian metabolism, RNA viral analysis, viral proteins analysis, viral proteins biosynthesis, centrifugation, density gradient, genetic complementation test, immune sera, peptides analysis, recombination, genetic, ribonucleases.

Klimov, A.I., S.G. Markushin, S. Prosch, V.P. Ginzburg, H. Heider, A.M. Heider, C. Schroeder, and R.G. Webster (1992). Relation between drug resistance and antigenicity among norakin-resistant mutants of influenza A (fowl plague) virus. Archives of Virology 124(1-2): 147-55.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Norakin-resistant (NR) mutants of fowl plague virus (A/FPV/Weybridge, H7N7) have 1 to 2 (in one instance 3) amino acid substitutions in different positions of the heavy (HA 1) and/or light (HA 2) subunits of the haemagglutinin (HA) molecule. Investigation of NR mutants using the haemagglutination inhibition test with monoclonal antibodies (MAb) to the HA of A/seal/Massachusetts/80 (H7N7) virus revealed that one of the mutants (NR 1) differs antigenically from the wild-type fowl plague virus: its haemagglutination was not inhibited by MAb 55/2 and 58/6. By contrast, MAb-resistant (escape) mutants, selected from the wild-type fowl plague virus under pressure from MAb 55/2 or 58/6, showed reduced drug sensitivity. These findings suggest a possibility of correlation between alteration of influenza virus antigenicity and change of its sensitivity to drugs whose target is the haemagglutinin. This potential effect should be taken into account when antiviral substances directed to surface influenza virus antigens are being developed for use as antiviral drugs.

            Descriptors:  drug resistance, microbial genetics, fowl plague genetics, hemagglutinins viral genetics, influenza A virus avian genetics, piperidines pharmacology, amino acid sequence,  antibodies, monoclonal immunology, chick embryo, epitopes immunology, fowl plague immunology, hemagglutinin glycoproteins, influenza virus, influenza A virus avian drug effects, influenza A virus avian immunology, molecular sequence data, mutation genetics.

Klimov, A.I., R.I.A. Podcherniaeva, G.A. Danlybaeva, V.V. Iaros, and K.V. Lisovskaia (1992). Reproduktsiia reassortantov virusov grippa A i B s izvestnym sostavom genoma v razlichnykh kletochnykh sistemakh. [The reproduction of reassortant influenza A and B viruses with a known genome composition in different cell systems]. Voprosy Virusologii 37(1): 31-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Reproduction of parental strains and reassortants (with known genome composition) of influenza A and B viruses was studied in chick embryos (CE) and in different cell lines (SPEV, MDCK, BHK-21, M22, etc.). The results agree with the concept that the yield of influenza A virus in CE depends on its M-gene. At the same time, the experimental results suggest that reproduction of influenza B virus in the same system is not determined by M-gene. Reproduction (hr-phenotype) of influenza A and B viruses in cell cultures was shown to be determined not only by the gene coding for hemagglutinin but also by other virus genes, the reproduction level being dependent on different genes in different cell systems.

            Descriptors:  genome, viral, influenza A virus avian physiology, influenza B virus physiology, reassortant viruses physiology, virus replication physiology, cell line, influenza A virus avian genetics, influenza B virus genetics, reassortant viruses genetics, virus cultivation, virus replication genetics.

Kobasa, D., K. Wells, and Y. Kawaoka (2001). Amino acids responsible for the absolute sialidase activity of the influenza A virus neuraminidase: relationship to growth in the duck intestine. Journal of Virology 75(23): 11773-80.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The 1957 human pandemic strain of influenza A virus contained an avian virus hemagglutinin (HA) and neuraminidase (NA), both of which acquired specificity for the human receptor, N-acetylneuraminic acid linked to galactose of cellular glycoconjugates via an alpha2-6 bond (NeuAcalpha2-6Gal). Although the NA retained considerable specificity for NeuAcalpha2-3Gal, its original substrate in ducks, it lost the ability to support viral growth in the duck intestine, suggesting a growth-restrictive change other than a shift in substrate specificity. To test this possibility, we generated a panel of reassortant viruses that expressed the NA genes of human H2N2 viruses isolated from 1957 to 1968 with all other genes from the avian virus A/duck/Hong Kong/278/78 (H9N2). Only the NA of A/Singapore/1/57 supported efficient viral growth in the intestines of orally inoculated ducks. The growth-supporting capacity of the NA correlated with a high level of enzymatic activity, comparable to that found to be associated with avian virus NAs. The specific activities of the A/Ann Arbor/6/60 and A/England/12/62 NAs, which showed greatly restricted abilities to support viral growth in ducks, were only 8 and 5%, respectively, of the NA specific activity for A/Singapore/1/57. Using chimeric constructs based on A/Singapore/1/57 and A/England/12/62 NAs, we localized the determinants of high specific NA activity to a region containing six amino acid substitutions in A/England/12/62: Ser331-->Arg, Asp339-->Asn, Asn367-->Ser, Ser370-->Leu, Asn400-->Ser, and Pro431-->Glu. Five of these six residues (excluding Asn400) were required and sufficient for the full specific activity of the A/Singapore/1/57 NA. Thus, in addition to a change in substrate specificity, a reduction in high specific activity may be required for the adaptation of avian virus NAs to growth in humans. This change is likely needed to maintain an optimal balance between NA activity and the lower affinity shown by human virus HAs for their cellular receptor.

            Descriptors:  influenza A virus avian enzymology, intestines virology, neuraminidase metabolism, virus replication, amino acid substitution,  base sequence, DNA primers, ducks, avian growth and development, avian physiology, models, molecular, mutagenesis, site directed, neuraminidase chemistry, neuraminidase genetics, reassortant viruses enzymology, reassortant viruses genetics, reassortant viruses growth and development, reassortant viruses physiology.

Kobasa, D., M.E. Rodgers, K. Wells, and Y. Kawaoka (1997). Neuraminidase hemadsorption activity, conserved in avian influenza A viruses, does not influence viral replication in ducks. Journal of Virology 71(9): 6706-6713.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The N1 and N9 neuraminidase (NA) subtypes of influenza A viruses exhibit significant hemadsorption activity that localizes to a site distinct from that of the enzymatic active site. To determine the conservation of hemadsorption activity among different NAs, we have examined most of the NA subtypes from avian, swine, equine, and human virus isolates. All subtypes of avian virus NAs examined and one equine virus N8 NA possessed high levels of hemadsorption activity. A swine virus N1 NA exhibited only weak hemadsorption activity, while in human virus N1 and N2 NAs, the activity was detected at a much lower level than in avian virus NAs. NAs which possessed hemadsorption activity for chicken erythrocytes (RBCs) were similarly able to adsorb human RBCs. However, none of the hemadsorption-positive NAs could bind equine, swine, or bovine RBCs, suggesting that RBCs from these species lack molecules, recognized by the NA hemadsorption site, present on human and chicken RBCs. Mutagenesis of the putative hemadsorption site of A/duck/Hong Kong/7/75 N2 NA abolished the high level of hemadsorption activity exhibited by the wild-type protein but also resulted in a 50% reduction of the NA enzymatic activity. A transfectant virus, generated by reverse genetics, containing this mutated NA replicated 10-fold less efficiently in chicken embryo fibroblast cultures than did a transfectant virus expressing the wild-type NA. However, both viruses replicated equally well in Peking ducks. Although conservation of NA hemadsorption activity among avian virus NAs suggests the maintenance of a required function of NA, loss of the activity does not preclude the replication of the virus in an avian host.

            Descriptors:  biochemistry and molecular biophysics, blood and lymphatics, cell biology, enzymology, genetics, infection, microbiology, skeletal system, A, duck, Hong Kong, 7, 75, blood and lymphatics enzymology, erythrocyte fibroblasts, hemadsorption activity, host infection, influenza A viruses, N1 neuraminidase, N9 neuraminidase, Peking duck, viral replication, viral surface, glycoprotein.

Kocan, A.A., G.A. Daubney, and K.M. Kocan (1978). Structural changes associated with type-A influenza in Mallard duck tracheal organ culture. Avian Diseases 22(3): 535-41.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Mallard duck tracheal organ cultures were used to study structural changes associated with infection with type-A influenza (A/Turkey/WIS/68) (H9N2) at the light-microscope and electron-microscope levels. Light-microscope changes in infected organ culture were cytoplasmic vacuolization, nuclear swelling, reduction in ciliated epithelium, and sloughing of epithelial cells. Ultrastructural changes included the loss of cilia and microvilli, distortion and swelling of cellular organelles, breakdown of intercellular junction, and apparent phagocytosis of the ciliated epithelium. Numerous budding virions were noted at the plasmalemma. Virus was detected by egg inoculation from all experimental cultures throughout the 192-hour experiment.

            Descriptors:  influenza A virus, avian growth and development, trachea ultrastructure, organ culture, trachea microbiology.

Kodihalli, S., J.R. Haynes, H.L. Robinson, and R.G. Webster (1997). Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin.  Journal of Virology 71(5): 3391-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Inoculation of mice with hemagglutinin (HA)-expressing DNA affords reliable protection against lethal influenza virus infection, while in chickens the same strategy has yielded variable results. Here we show that gene gun delivery of DNA encoding an H5 HA protein confers complete immune protection to chickens challenged with lethal H5 viruses. In tests of the influence of promoter selection on vaccine efficacy, close correlations were obtained between immune responses and the dose of DNA administered, whether a cytomegalovirus (CMV) immediate-early promoter or a chicken beta-actin promoter was used. Perhaps most important, the HA-DNA vaccine conferred 95% cross-protection against challenge with lethal antigenic variants that differed from the primary antigen by 11 to 13% (HA1 amino acid sequence homology). Overall, the high levels of protection seen with gene gun delivery of HA-DNA were as good as, if not better than, those achieved with a conventional whole-virus vaccine, with fewer instances of morbidity and death. The absence of detectable antibody titers after primary immunization, together with the rapid appearance of high titers immediately after challenge, implicates efficient B-cell priming as the principal mechanism of DNA-mediated immune protection. Our results suggest that the efficacy of HA-DNA influenza virus vaccine in mice extends to chickens and probably to other avian species as well. Indeed, the H5 preparation we describe offers an attractive means to protect the domestic poultry industry in the United States from lethal H5N2 viruses, which continue to circulate in Mexico.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian immunology, influenza vaccine immunology, vaccines, DNA immunology, antibodies, viral blood, biolistics, chickens, dose response relationship, immunologic, epitopes, fowl plague prevention and control, hemagglutinin glycoproteins, influenza virus immunology, promoter regions genetics, vaccination.

Kodihalli, S., V. Sivanandan, K.V. Nagaraja, D. Shaw, and D.A. Halvorson (1994). Effect of avian influenza virus infection on the phagocytic function of systemic phagocytes and pulmonary macrophages of turkeys. Avian Diseases 38(1): 93-102.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The effects of avian influenza virus (AIV) infection on systemic phagocytes and pulmonary macrophages of turkeys were studied. There was a significant increase (P < 0.0001) in oxidative burst in systemic phagocytes of AIV-inoculated turkeys on 2, 4, 6, and 8 days postinoculation (PI), as measured by chemiluminescence. There was also a significant increase (P < 0.02) in oxidative burst in pulmonary macrophages on day 4 PI. The chemiluminescence response was depressed on 6, 8, and 10 days PI in AIV-inoculated turkeys compared with controls. The increase in oxidative response in both systemic phagocytes and pulmonary macrophages correlated with the peak virus titer in the lungs and trachea of AIV-inoculated turkeys. Bacterial killing by pulmonary macrophages from AIV-inoculated turkeys was reduced on days 6 and 10 PI compared with uninoculated controls. Histopathological changes in trachea were more pronounced on day 6 PI in AIV-inoculated turkeys; no significant changes were detected in the lungs. These data indicate that compromised functional capacity of pulmonary macrophages predisposes turkeys to secondary bacterial infections.

            Descriptors:  turkeys, avian influenza virus, phagocytes, macrophages, immune response, histopathology, lungs, trachea, antimicrobial properties, animal morphology, antibiotic properties, birds, cells, Galliformes, immunity, influenza virus, pathology, phagocytes, respiratory system, viruses, oxidative burst, phagocytosis, immune competence, antibacterial properties.

Korbecki, M. (1973). Dzialanie 2-(N-D-glukozyloamino)-5-(3-pirydylo)-1,3,4-oksadiazolu na replikacje wirusa pomoru drobiu w hodowli komorkowej. [Effect of 2-(N-D-glucosylamino)-5-(3-pyridilo)-1,3,4-oxadiazole on replication of fowl plague virus in cell culture]. Medycyna Doswiadczalna i Mikrobiologia 25(4): 335-8.  ISSN: 0025-8601.

            Descriptors:  influenza A virus avian drug effects, oxadiazoles pharmacology, virus replication drug effects, cultured cells, chick embryo, cytopathogenic effect, viral, fibroblasts.

Kornilaeva, G.V. and A.G. Bukrinskaia (1980). Deproteinizatsiia virusa grippa zarazhaemymi kletkami pri 4 gradusa C. [Deproteinization of the influenza virus by infected cells at 4 degrees C]. Voprosy Virusologii (6): 701-5.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The process of influenza virus deproteinization was compared in two systems: chick fibroblasts infected with fowl plague virus (FPV) and MDCK cells infected with WSN virus. The cells were infected with 3H-uridine-labeled viruses. Deproteinization of virus structures was studied at 4 degrees C and after incubation of virus-infected cells at 37 degrees C. At 4 degrees C, the bulk of radioactivity of the original virus was found in the perinuclear cytoplasm (the fraction obtained by treatment of triton X-100-purified nuclei with 0.1 M citric acid) and much less radioactivity was found in the nucleus. After incubation at 37 degrees C the level of radioactivity in the nucleus increased and reached or even exceeded that in the perinuclear cytoplasm. A biophysical analysis of the structures showed the perinuclear cytoplasm to contain subviral particles (SVP) similar to nucleoids as well as RNP with a buoyant density of 1.35 g/ml in cesium chloride. The nuclear extract contained RNP with a buoyant density 1.39-1.41 m/ml. The experimental results indicate that the first stage of deproteinization of virus particles to SVP occurs at 4 degrees C. The second stage of deproteinization, to RNP with a buoyant density 1.35 g/ml, also occurs at a low temperature.

            Descriptors:  orthomyxoviridae metabolism, temperature, viral proteins metabolism, chick embryo, influenza A virus avian metabolism, ribonucleoproteins metabolism, time factors, tritium,  virus cultivation.

Kornilaeva, G.V., E.V. Molibog, and A.G. Bukrinskaia (1983). pH-zavisimost' gemoliticheskoi i neiraminidaznoi aktivnosti chuvstvitel'nykh i ustoichivykh k remantadinu variantov virusa grippa. [pH-dependent hemolytic and neuraminidase activity of remantadine-sensitive and -resistant variants of influenza virus]. Voprosy Virusologii 28(1): 30-2.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A comparative study of pH-dependence of hemolytic and neuraminidase activities of four remantadin-sensitive influenza A virus strains CAPV (classical avian plague virus) (H7N7), USSR/090/77 (H1N1), Ann Arbor (H2N2), and Texas (H3N2) and their remantadin-resistant variants was carried out. The original strains were shown to produce hemolysis in a narrow pH range (5.0 and 5.5) and to have maximal neuraminidase activity at the same pH values. In remantadin-resistant variants the optimal pH values for hemolytic and neuraminidase activities were higher by 0.5-1.0 than for the sensitive variants.

            Descriptors:  adamantane analogs and derivatives, hemolysis, influenza A virus enzymology, neuraminidase metabolism, rimantadine pharmacology, variation genetics drug effects, drug resistance, microbial, hydrogen-ion concentration, influenza A virus avian drug effects, avian enzymology, influenza A virus drug effects.

Kornilaeva, G.V., V.A. Slepushkin, and A.G. Bukrinskaia (1986). Raznaia priroda kletochnykh retseptorov dlia virusov grippa i paragrippa. [Varying nature of the cell receptors for influenza and para-influenza viruses]. Voprosy Virusologii 31(1): 35-9.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A comparative study of receptors for influenza virus, fowl plague virus, and human parainfluenza type 3 virus was carried out. Natural receptors of guinea pig erythrocytes were destroyed with neuraminidase, and individual gangliosides GM1, GD1a, and GT1b were inserted into their membranes. The labeled virus was adsorbed on the erythrocytes modified in this manner, and the degree of restoration of the receptor activity of erythrocytes lost after neuraminidase treatment was determined. Two gangliosides, GD1a and GT1b, were found to be capable of functioning as specific receptors for influenza virus. Both gangliosides restored completely the virus adsorption on erythrocytes. In contrast, none of the three gangliosides used did not restore parainfluenza virus adsorption. It is concluded that the nature of influenza and parainfluenza virus receptors is different.

            Descriptors:  influenza A virus avian metabolism, orthomyxoviridae metabolism, parainfluenza virus 3, human metabolism, receptors, virus metabolism, respirovirus metabolism, adsorption, cell line, erythrocytes drug effects, erythrocytes metabolism, erythrocytes microbiology, gangliosides metabolism, guinea pigs, neuraminidase pharmacology, receptors, virus drug effects, virus cultivation.

Kortt, A.A., E. Nice, and L.C. Gruen (1999). Analysis of the binding of the Fab fragment of monoclonal antibody NC10 to influenza virus N9 neuraminidase from tern and whale using the BIAcore biosensor: effect of immobilization level and flow rate on kinetic analysis. Analytical Biochemistry 273(1): 133-41.  ISSN: 0003-2697.

            NAL Call Number:  381 An13

            Descriptors:  antibodies, monoclonal metabolism, biosensing techniques methods, immunoglobulin fragments immunology, immunoglobulins, fab immunology, influenza A virus avian enzymology, neuraminidase immunology, birds, avian immunology, kinetics, neuraminidase metabolism, protein binding, whales.

Kosiakov, P.N., V.S. Pankratov, and Z.I. Rovnova (1979). Antigeny gemaggliutininov virusov grippa, vydelennykh ot cheloveka i ptits. [Hemagglutinin antigens of influenza viruses isolated from man and birds]. Voprosy Virusologii (3): 242-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Immunological analysis has shown hemagglutinins of avian viruses like hemagglutinins of human viruses to have a complex antigenic composition. Three antigenic determinants were discovered in hemagglutinin of A/Chicken/12/71 virus previously designated H3 and in hemagglutinin of A/Tern/18/73 virus previously designated Hav7. The H3 determinant and the second determinant are identical in avian and A/Hong Kong/1/68 human viruses. In addition, hemagglutinins of avian viruses have a determinant specific for each virus which is lacking in human influenza virus hemagglutinin.

            Descriptors:  antigens, viral isolation and purification, birds microbiology, hemagglutinins viral isolation and purification, influenza A virus avian immunology, human immunology, adsorption, chick embryo, complement fixation tests, epitopes, hemagglutination inhibition tests.

Kraus, A.A. and C. Scholtissek (1974). Purification and characterization of a ribonuclease inhibitor of chick-embryo cells. European Journal of Biochemistry FEBS 48(2): 345-50.  ISSN: 0014-2956.

            NAL Call Number:  QP501.E8

            Descriptors:  DNA directed RNA polymerases antagonists and inhibitors, DNA directed RNA polymerases blood, enzyme inhibitors isolation and purification, ribonucleases antagonists and inhibitors, centrifugation, density gradient, chick embryo, chromatography, affinity, cytoplasm enzymology, cytosol,  electrophoresis, polyacrylamide gel, hydrogen-ion concentration, influenza A virus avian enzymology, kinetics, molecular weight, orthomyxoviridae enzymology.

Kretzschmar, E., M. Veit, S. Brunschon, K. Kuroda, and H.D. Klenk (1992). Secretion of fowl plague virus haemagglutinin from insect cells requires elimination of both hydrophobic domains. Journal of General Virology 73(Pt. 4): 839-48.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  In the present study we have investigated the role of the hydrophobic domains of the fowl plague virus (FPV) haemagglutinin (HA) on its intracellular transport and maturation in insect cells. To this end processing of full-length HA (A+) has been compared to that of two truncated forms lacking either the cytoplasmic domain and the transmembrane domain (A-) or lacking the entire HA2 subunit, i.e. the transmembrane domain and the fusion peptide (HA2-). All glycosylation sites present on A- and HA2- were glycosylated, indicating that both truncated forms were completely translocated in the endoplasmic reticulum. Unlike A+, A- and HA2- did not form trimers as indicated by cross-linking, gradient centrifugation and studies employing conformation-specific antibodies. Whereas HA2- was efficiently secreted, A- was retained in the cells in an apparently membrane-bound form. The data show that the carboxy-terminal transmembrane region is essential for the formation and stability of the trimers of the FPV HA. These observations also indicate that, under certain conditions, the fusion peptide of the FPV HA can serve as a membrane anchor.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian metabolism, protein processing, post translational, viral envelope proteins secretion, base sequence, biological transport, active, cell fractionation, cultured cells, DNA mutational analysis, endopeptidases metabolism, glycosylation, hemagglutinin glycoproteins, influenza virus, avian genetics, insects, molecular sequence data, protein conformation, recombinant proteins biosynthesis, structure activity relationship.

Kuiken, T., G. Rimmelzwaan, D. van Riel, G. van Amerongen, M. Baars, R. Fouchier, and A. Osterhaus (2004). Avian H5N1 influenza in cats. Science 306(5694): 241.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Abstract:  During the 2003 to 2004 outbreak of avian influenza A (H5N1) virus in Asia, there were anecdotal reports of fatal infection in domestic cats, although this species is considered resistant to influenza. We experimentally inoculated cats with H5N1 virus intratracheally and by feeding them virus-infected chickens. The cats excreted virus, developed severe diffuse alveolar damage, and transmitted virus to sentinel cats. These results show that domestic cats are at risk of disease or death from H5N1 virus, can be infected by horizontal transmission, and may play a role in the epidemiology of this virus.

            Descriptors:  cat diseases virology, influenza veterinary, influenza A virus, avian pathogenicity, cat diseases pathology, cat diseases transmission, cats, chickens virology, disease transmission, horizontal veterinary, feeding behavior, influenza pathology, influenza transmission, influenza virology, influenza A virus, avian isolation and purification, avian influenza virology, pulmonary alveoli pathology, pulmonary alveoli virology.

Kul'kova, L.V. and V.Z. Soloukhin (1979). Reproduktsiia virusa istinnoi chumy ptits v organizme komarov Aedes aegypti. [Classical fowl plague virus reproduction in the body of Aedes aegypti mosquitoes]. Voprosy Virusologii (6): 652-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The results of the studies on fowl plague virus (FPV, Rostok strain) reproduction in Aedes aegypti mosquitoes are presented. The virus-containing allantoic fluid was inoculated intrathoracally in volumes of 0.1 and 0.2 microliter. The virus was isolated in chick embryos and could be detected at 5--14 days after inoculation. After inoculation of 0.1 microliter of virus it could be detected in doses of 0.5, 2.0, 1.75 Ig2 ID50, after inoculation of 0.2 microliter--in doses of 5, 1.5, and 0.5 Ig2 ID50.

            Descriptors:  Aedes microbiology, influenza A virus avian physiology, time factors, virus replication.

Kurinenko, B.M., N.V. Kalacheva, and P.I.U. Muratov (1995). Poluchenie i protivovirusnye svoistva ribonukleazy Bacillus intermedius, modifitsirovannoi khlorangidridom adamantankarbonovoi kisloty. [Preparation and antiviral properties of Bacillus intermedius ribonuclease modified by chloranhydride of adamantanecarboxylic acid]. Antibiotiki i Khimioterapiia Antibiotics and Chemoterapy [Sic] Ministerstvo Meditsinskoi i Mikrobiologicheskoi Promyshlennosti SSSR 40(9): 17-9.  ISSN: 0235-2990.

            NAL Call Number:  RM265.A5125

            Abstract:  Bacillus intermedius ribonuclease modified by the residue of adamantane carboxylic acid was prepared. When the cells of chick embryo fibroblasts infected by the fowl plague virus were exposed to the modified ribonuclease, the antiviral activity proved to be higher by comparison to that of the native enzyme. The chemotherapeutic index of the RNAse after the modification increased 4 times.

            Descriptors:  adamantane analogs and derivatives, antiviral agents isolation and purification, Bacillus enzymology, ribonucleases isolation and purification, adamantane chemistry, antiviral agents pharmacology, chick embryo, fibroblasts drug effects, fowl plague drug therapy, influenza A virus avian drug effects, molecular structure, ribonucleases chemistry, ribonucleases pharmacology.

Kuroda, K., A. Groner, K. Frese, D. Drenckhahn, C. Hauser, R. Rott, W. Doerfler, and H.D. Klenk (1989). Synthesis of biologically active influenza virus hemagglutinin in insect larvae. Journal of Virology 63(4):  1677-85.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The hemagglutinin of influenza (fowl plague) virus was expressed in larvae of Heliothis virescens by using recombinant Autographa californica nuclear polyhedrosis virus (AcNPV) as a vector. Animals were infected with the recombinant virus either by parenteral injection or by feeding. For oral uptake, recombinant virus occluded in polyhedra obtained from cultured Spodoptera frugiperda cells after coinfection with authentic AcNPV was used. Immunohistological analyses of infected animals revealed that the hemagglutinin was expressed only in those tissues that are also permissive for the replication of authentic AcNPV. These tissues included hypodermis, fat body, and tracheal matrix. After oral infection, hemagglutinin was also detected in individual gut cells. The amount of hemagglutinin synthesized in larvae after parenteral infection was 0.3% of the total protein, compared with 5% obtained in cultured insect cells. The hemagglutinin was transported to the cell surface and expressed in polarized cells only at the apical plasma membrane. It was processed by posttranslational proteolysis into the cleavage products HA1 and HA2. Oligosaccharides were attached by N-glycosidic linkages and were smaller than those found on hemagglutinin obtained from vertebrate cells. Hemagglutinin from larvae expressed receptor binding and cell fusion activities, but quantitation of the hemolytic capacity revealed that it was only about half as active as hemagglutinin from vertebrate or insect cell cultures. Chickens immunized with larval tissues containing hemagglutinin were protected from infection with fowl plague virus. These observations demonstrate that live insects are able to produce a recombinant membrane protein of vertebrate origin in biologically active form.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian immunology, insect viruses genetics, administration, oral, blotting, western, cloning, molecular, DNA, recombinant, genetic vectors, hemolysis, avian genetics, larva, Lepidoptera, membrane glycoproteins genetics, recombinant proteins genetics.

Kuroda, K., M. Veit, and H.D. Klenk (1991). Retarded processing of influenza virus hemagglutinin in insect cells. Virology 180(1): 159-65.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  When expressed in Spodoptera frugiperda cells by a baculovirus vector, the hemagglutinin of fowl plague virus has been found to contain palmitic acid in covalent hydroxylamine-sensitive linkage, indicating that these cells have the capacity to acylate foreign proteins at cysteine residues. Centrifugation on sucrose density gradients and immune precipitation with conformation-specific antibodies were used to compare trimerization of the hemagglutinin in insect cells and in fowl plague virus-infected MDCK cells. Trimerization of the hemagglutinin was incomplete in insect cells, and the kinetics of this reaction were about three times slower than in vertebrate cells. Similarly, post-translational proteolytic cleavage occurred in insect cells with a half-time of 90 min, and a substantial fraction of the hemagglutinin persisted in uncleaved form. In contrast, hemagglutinin was almost completely cleaved in MDCK cells, and the half-time of cleavage was only 30 min. The data indicate that in insect cells trimerization and, as a result, the subsequent processing steps of the hemagglutinin, are retarded and less efficient. The possible roles of aberrant glycosylation, acidic milieu, and lack of other influenza virus proteins in hemagglutinin trimerization are discussed.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian metabolism, acylation, antibodies, monoclonal, biological transport, cell line, centrifugation, density gradient, electrophoresis, polyacrylamide gel, eukaryotic cells, fatty acids metabolism, avian growth and development, kinetics, moths cytology, polymers, precipitin tests, protein processing, post translational.

L'vov, D.K., R.I.A. Podcherniaeva, R. Webster, M.V. Ronina, and T.V. Pysina (1979). Poluchenie rekombinantov, antigenno identichynykh tsirkuliruiushchim v prirode shtammam virusa grippa. [Production of recombinants antigenically identical to influenza virus strains circulating in nature]. Voprosy Virusologii (5): 493-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Recombination of a human influenza virus with an avian influenza virus produced a H2Nav2 recombinant with the antigenic properties analogous to those of avian influenza virus (H2Nav2) isolated from wild ducks in the Far East, USSR. Recombination of two avian influenza viruses yielded a recombinant H2N2, an antigenic analogues of influenza A/Singapore/1/57 (H2N2) virus which had started an epidemic of influenza in 1957.

            Descriptors:  antigens, viral genetics, influenza A virus genetics, recombination, genetic, animals, wild, crosses, genetic, ducks microbiology, hemagglutination inhibition tests, influenza A virus human genetics, neuraminidase antagonists and inhibitors.

Lambkin, R. and N.J. Dimmock (1995). All rabbits immunized with type A influenza virions have a serum haemagglutination-inhibition antibody response biased to a single epitope in antigenic site B. Journal of General Virology 76(Pt. 4): 889-97.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Nine rabbits were immunized with type A influenza virions and the epitope specificities of the secondary serum haemagglutination-inhibition (HI) antibody response were analysed with a panel of neutralizing monoclonal (MAb) antibody double escape mutants. Each of the latter was made by sequential selection using a MAb directed to an epitope of a discrete antigenic site, site A, site B or site D, of the haemagglutinin (HA). Thus the epitope reactivity of the escape mutants was represented as A+ B- D-, A- B+ D- and A- B- D+. The HI antibody response of all antisera was biased to the site B epitope. In 9/12 antisera, obtained from seven rabbits immunized with whole virions, the site B epitope was predominant, representing 65-82% of the total HI antibody. The restriction of HI antibody was unaffected by strain of rabbit, route of inoculation (intravenous or subcutaneous), use of Freund's adjuvant, and up to four immunizing injections. In 3/7 rabbits immunized with whole virus, there was a HI antibody response to the HC2 (site A) or HC10 (site D) epitope, but not both, of equal magnitude to the site B epitope. The HI antibody response in one of the rabbits (#40) became more biased to the site B epitope between the third and fourth immunizing doses. Two further rabbits were immunized with virions which had been partially digested with bromelain and then purified from free HA. Both of these made equal HI antibody responses to the site B epitope and the site D epitope, possibly because their remaining HA spikes were better exposed. Overall, these data demonstrate an unexpected degree of restriction in the production of biologically relevant antibody, such that some rabbits (e.g. #45) mount an HI antibody response which is essentially epitope-specific. Implications for epitope specificity of HI antibody stimulated by human influenza vaccines, and also for the generation of antigenic drift variants are discussed. The reason for the non-responsiveness of the immune system to the many other HI epitopes of the HA is not known.

            Descriptors:  antibodies, viral immunology, antibody specificity immunology, antigens, viral immunology, epitopes immunology, influenza A virus avian immunology, antibodies, viral blood, binding sites, cell line, chick embryo, dogs, hemagglutination inhibition tests, immunization, neutralization tests, rabbits, virion immunology.

Lambkin, R., L. McLain, S.E. Jones, S.L. Aldridge, and N.J. Dimmock (1994). Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift. Journal of General Virology 75(Pt. 12): 3493-502.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  It is not fully understood how antigenic drift of the haemagglutinin of type A influenza virus in man occurs in the presence of the expected polyclonal antibody response to the five antigenic sites, A to E. Here we show that 12% (11/92) of sera from mice which had mounted a secondary immune response to inactivated influenza virus were able to select escape mutants. No escape mutant was selected with serum from nonimmunized mice (0/65). Selection required only a single passage, and escape mutants were identified by their reaction with monoclonal antibodies (MAbs); all but one had altered reactivity at site A. Most of the site A escape mutants (7/10) were conventional in character and did not react in haemagglutination-inhibition (HI) or neutralization assays with the identifying MAb. The HA genes of three of these were part sequenced and had a predicted single amino acid substitution (Gly-144-->Glu) in site A. The other escape mutants (3/10) had a small (2-fold) reduction in HI and neutralization to the site A MAb, but no amino acid substitution in site A. The final mutant was a conventional site B escape mutant. To model antisera which selected escape mutants, we constructed 'pseudo-immune sera' using mixtures of two neutralizing MAbs in which the first MAb was held at a constant high concentration (1000 HIU/ml). Escape mutants could be selected to the first MAb when the titre of the second MAb was reduced to a low but still inhibiting concentration (1 to 3 HIU/ml). Mixtures of three MAbs also selected escape mutants with similar facility provided that the second and third MAbs were reduced to a similar low concentration. Thus it is possible that the ability of an antiserum to select escape mutants is due to the neutralizing antibody response being biased to an epitope/cross-reacting epitopes within a single antigenic site. However, when escape mutants were reacted in HI assay with their selecting antiserum, the maximum difference from the titre with wt virus was 75%. The findings of this study may be relevant to the understanding of antigenic drift in type A human influenza virus, and to immune-driven antigenic variation in other virus infections.

            Descriptors:  antibodies, monoclonal immunology, antigenic variation genetics, hemagglutinins viral genetics, immune sera, influenza A virus avian immunology, point mutation, antibodies, viral blood, DNA mutational analysis, epitopes analysis, gene frequency genetics,  genes, structural, viral genetics, hemagglutination inhibition tests, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, immunization, avian genetics, mice, mice inbred BALB c, mice, inbred c3h, neutralization tests, selection genetics, viral envelope proteins genetics, viral envelope proteins immunology.

Lau, S.C. and C. Scholtissek (1995). Abortive infection of Vero cells by an influenza A virus (FPV). Virology 212(1): 225-31.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  We have discovered a new type of abortive replication in Vero cells infected with fowl plague virus. In these cells there is an enhanced splicing of the colinear mRNAs of segment 7 and presumably also of segment 8, leading to an extreme overproduction of M2 and NS2 proteins. The cleavage of the hemagglutinin (HA) into HA1 and HA2 and the processing of its carbohydrate side chains are markedly retarded and incomplete. Although some of the HA is incorporated into the plasma membrane, leading to a positive hemadsorption, most of it accumulates in a discrete compartment close to the nuclear membrane, representing presumably the reticuloendothel and/or the Golgi network. Neuraminidase activity in Vero cells is extremely low. The nucleoprotein is normally released from nuclei late in infection. Very little infectious virus is released, and its spread is highly impeded.

            Descriptors:  gene expression regulation, viral, influenza A virus avian growth and development, vero cells microbiology, cultured cells, Cercopithecus aethiops, chick embryo, RNA, messenger metabolism, viral metabolism, time factors, viral proteins metabolism, virus replication.

Laudert, E., D. Halvorson, V. Sivanandan, and D. Shaw (1993). Comparative evaluation of tissue trophism characteristics in turkeys and mallard ducks after intravenous inoculation of type A influenza viruses. Avian Diseases 37(3): 773-80.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Ten avian type A influenza viruses consisting of seven waterfowl-origin, one pheasant-origin, and two turkey-origin viruses were evaluated for their pathogenicity potential after intravenous inoculation into domestic turkeys and mallard ducks (Anas platyrhynchos). The replicative abilities and tissue trophism properties of each virus isolate were examined in both species. The overall virus-isolation rate and histopathological lesion score were greater in the turkeys than in the ducks. The waterfowl-origin viruses caused more tissue damage in turkeys than in ducks but had a narrower tissue distribution range. The pheasant isolate was extremely pathogenic in turkeys but had limited distribution and little effect in ducks. The turkey isolates were more pathogenic in turkeys than in ducks. The pancreas was the most severely affected organ in turkeys, followed by kidney and liver. The spleen and bursa were the most commonly affected organs in ducks.

            Descriptors:  ducks microbiology, fowl plague microbiology, influenza A virus avian pathogenicity, turkeys microbiology, fowl plague pathology, avian isolation and purification, avian physiology, injections, intravenous, kidney microbiology, kidney pathology, organ specificity, pancreas microbiology, pancreas pathology, species specificity, spleen microbiology, spleen pathology, virus replication.

Laudert, E., V. Sivanandan, and D. Halvorson (1993). Effect of an H5N1 avian influenza virus infection on the immune system of mallard ducks. Avian Diseases 37(3): 845-53.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Avian influenza virus (AIV) of waterfowl origin, A/Mallard/Ohio/184/86 (H5N1), was used to evaluate the effect of AIV infection on the functional capabilities of the immune system in mallard ducks. The three main arms of the immune system--humoral, cell-mediated, and cellular--were evaluated. The integrity of the humoral immune system after AIV infection was evaluated by measuring total immunoglobulin and IgG antibody production to sheep erythrocytes and Brucella abortus antigen using hemagglutination and microagglutination assays, respectively. Cell-mediated immunity was evaluated using mitogen/antigen stimulation assays, and by measuring the cutaneous basophilic hypersensitivity response to intradermal phytohemagglutinin-P inoculation. The cellular component of the immune response was evaluated using whole-blood chemiluminescence and bacterial clearance assays. Results showed that infection with this AIV isolate suppressed T-cell function and enhanced macrophage phagocytic activity.

            Descriptors:  bird diseases immunology, ducks, fowl plague immunology, basophils immunology, Escherichia coli infections complications, Escherichia coli infections immunology, Escherichia coli infections veterinary, fowl plague complications, fowl plague etiology, hypersensitivity, delayed, immunoglobulin g metabolism,  immunoglobulins metabolism, influenza A virus avian immunology, avian isolation and purification, avian pathogenicity, lymphocyte activation, macrophages immunology, phagocytosis, T lymphocytes immunology.

Laudert, E., V. Sivanandan, D. Halvorson, D. Shaw, and R.G. Webster (1993). Biological and molecular characterization of H13N2 influenza type A viruses isolated from turkeys and surface water. Avian Diseases 37(3): 793-9.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The pathogenicity potential of two H13N2 influenza viruses, one isolated from turkeys and the other isolated from surface water, was evaluated in turkeys, chickens, and mallard ducks (Anas platyrhynchos ) after intracranial and oculonasal inoculation. Both isolates replicated in turkey poults, causing depressed weight gain, morbidity and mortality; both also caused histopathological lesions, such as mild to severe pancreatitis, hepatitis, and nephritis in turkeys. These isolates replicated in mallard ducklings but not in chickens. There was depressed weight gain in ducklings given the H13N2 isolate from water. Neither isolate caused morbidity or mortality in ducklings or chicks after inoculation.

            Descriptors:  influenza A virus avian isolation and purification, turkeys microbiology, water microbiology, antibodies, monoclonal, chickens, cross reactions, ducks, fowl plague etiology, fowl plague pathology, avian immunology, avian pathogenicity, species specificity, virulence.

Laver, W.G., P.M. Colman, R.G. Webster, V.S. Hinshaw, and G.M. Air (1984). Influenza virus neuraminidase with hemagglutinin activity. Virology 137(2): 314-23.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Isolated intact influenza virus neuraminidase (NA) molecules of the N9 subtype have been found to possess hemagglutinin (HA) activity which, at equivalent protein concentration, was fourfold higher than that of isolated hemagglutinin molecules of the H3 subtype. The amino-terminal sequence of the N9 NA is the same as in neuraminidases of the eight other influenza A virus NA subtypes previously reported. Viruses possessing N9 NA therefore have two different HA activities and antibody to either HA or NA alone was incapable of inhibiting hemagglutination by the virus. However, antibody to the HA of an H1N9 virus neutralized its infectivity as effectively as it neutralized H1N1 or H1N2 viruses whose neuraminidases have no HA activity. (Antibodies to N9 NA did not neutralize the infectivity of viruses with N9 neuraminidase). 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid inhibited N9 NA activity but had no effect on the HA activity of the isolated N9 NA. One interpretation of this result would be that the HA and NA activities are located in separate sites. Pronase-released N9 NA heads form crystals suitable for X-ray diffraction studies and preliminary data to 2.9 A establish the space group as cubic, I432 with cell dimension a = 184 A. Data extend to beyond 1.9 A resolution, and these will be collected in the future.

            Descriptors:  hemagglutinins viral, influenza A virus avian enzymology, neuraminidase isolation and purification, antibodies, monoclonal, antigen antibody complex, birds, hemagglutination tests, neuraminidase immunology, x-ray diffraction.

Laver, W.G. and R.G. Webster (1977). Hemagglutinin molecules of Hong Kong, equine-2, and duck/Ukraine influenza viruses lack N-terminal aspartic acid. Virology 81(2): 482-5.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  hemagglutinins viral analysis, influenza A virus avian immunology, human immunology, influenza A virus immunology, RNA viruses immunology, aspartic acid analysis, horses, recombination, genetic.

Lavrov, S.V., E.I. Eremkina, T.G. Orlova, G.A. Galegov, V.D. Soloviev, and V.M. Zhdanov (1968). Combined inhibition of influenza virus reproduction in cell culture using interferon and amantadine. Nature 217(131): 856-7.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Descriptors:  amantadine pharmacology, interferons pharmacology, orthomyxoviridae drug effects, chick embryo, cytopathogenic effect, viral, ethionine pharmacology, fluorouracil pharmacology, hemagglutination tests, influenza A virus avian drug effects, tissue culture, virus cultivation, virus inhibitors.

Lavrov, S.V., N.L. Pushkarsakia, and G.A. Galegov (1968). Ingibiruiushchee deistvie 1-adamantanamina na virus klassicheskoi chumy kur. [Inhibiting effect of 1-adamantamine on the classical fowl plague virus]. Voprosy Virusologii 13(3): 352-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  amantadine pharmacology, influenza A virus avian drug effects, chickens, cytopathogenic effect, viral.

Lazymova, Z.A., T.A. Asadullaev, E.S.h. Mamedov, and R.I.a. Akhverdieva (1988). Bis-(N,N'-uratsil-1-il)-selenoksometan: ingibitor virusa grippa. Voprosy Virusologii 33(2): 163-5.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Experimental studies of the influence of bis-(N,N'-uracil-1-yl)-selenoxomethane (I) and sodium selenite (II) on influenza virus reproduction on pieces of chorioallantoic membrane, both alone and in combination with remantadine and ribavirin, were carried out. The antiviral effects of both preparations were found to be enhanced in combination with effective and ineffective remantadine concentrations, whereas with ribavirin the additive effect was observed only in combination of the former preparation with ribavirin effective concentration. Combination of ribavirin with sodium selenite did not enhance the antiviral effect of the latter even when the effective concentration of nucleoside was used.

            Descriptors:  antimetabolites pharmacology, antiviral agents pharmacology, influenza A virus avian drug effects, organometallic compounds pharmacology, organoselenium compounds, uracil analogs and derivatives, chick embryo, drug synergism, fluorouracil pharmacology, avian physiology, ribavirin pharmacology, rimantadine pharmacology, selenious acid, selenium pharmacology, uracil pharmacology, virus replication drug effects.

Lecomte, J. and J.S. Oxford (1981). Detection of antigenic variation of influenza A matrix protein by a competitive radioimmunoassay. Journal of General Virology 57(Pt. 2): 403-6.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Antigenic relationships among the matrix proteins of influenza A viruses were analysed using a competitive radioimmunoassay technique. There were at least two antigenic determinants on the M protein of A/PR/8/34 virus. One antigenic determinant was shared by several influenza A viruses of human, avian, swine or equine origin, while the second determinant was not necessarily shared by all influenza viruses since it was not detected on the M protein of A/chicken/Germany/N/49 virus. In addition, the cross-reactive determinant(s) of the M protein of N virus was not equally represented in other influenza A virus subtypes.

            Descriptors:  influenza A virus human immunology, influenza A virus immunology, viral proteins immunology, cross reactions, epitopes, avian immunology, porcine immunology, radioimmunoassay, viral matrix proteins.

Ledovskikh, N.B., L.V. Iurchenko, G.A. Nevinskii, E.I. Frolova, E.M. Ivanova, A.A. Koshkin, N.A. Bulichev, V.F. Zarytova, and V.V. Vlasova ( 1992). Podavlenie transkriptsii RNK virusa grippa proizvodnymi oligonukleotidov. [Suppression of transcription of influenza virus RNA by oligonucleotide derivatives]. Molekuliarnaia Biologiia 26(3): 635-44.  ISSN: 0026-8984.

            NAL Call Number:  QH506.A1M62

            Abstract:  The inhibitory effects of oligonucleotide derivatives on the transcription of virus RNA in an in vitro system and synthesis of virus proteins was studied. Oligonucleotide derivatives d(T)3, d(T)4, d(T)8, d(T)10, d(CCAAACA), d(TCACCCTC), d(TTCCCATT), d(AATACTCT) and d(TGACCCTCTTCCCATT), that bear residues of ethidium, deuteroporphyrin and its complexes with Fe3+, hemin, cholesterol, deuterocholesterol, estrone and naphthoquinone at the 5'-end phosphate and/or at the 3'-end phosphate were studied. Unmodified oligonucleotides and their derivatives had a negligible effect on the synthesis of cellular proteins, but did inhibit the synthesis of influenza virus proteins. The majority of structural modifications increased the inhibitory effect of oligonucleotides. It was shown that the oligonucleotide derivatives carrying residues of porphyrin, quinone, ethidium, cholesterol, deuterotestosterone and estrone at concentrations near 10 mM inhibit virus development to 50-80%. A clear inhibitory effect (20-25%) of deuteroporphyrin, cholesterol and ethidium derivatives was revealed even at concentration 0.1 mM. The obtained results testified that the inhibition of influenza virus development is dependent on the interaction of oligonucleotide derivatives with the transcription complex proteins.

            Descriptors:  influenza A virus avian genetics, oligonucleotides pharmacology, RNA viral genetics, transcription, genetic drug effects, autoradiography, base sequence, cultured cells, chick embryo, genes viral, molecular sequence data, oligonucleotides chemistry, viral drug effects, viral proteins metabolism.

Lee, C.W., C.S. Song, Y.J. Lee, I.P. Mo, M. Garcia, D.L. Suarez, and S.J. Kim (2000). Sequence analysis of the hemagglutinin gene of H9N2 Korean avian influenza viruses and assessment of the pathogenic potential of isolate MS96. Avian Diseases 44(3): 527-35.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Sequence analysis of the hemagglutinin (HA) gene of five Korean H9N2 avian influenza virus (AIV) isolates showed that these viruses were closely related and possibly came from the same source. Phylogenetic analysis of the HA1 subunit of H9 subtype isolates revealed that Korean AIV isolates were different from isolates from the poultry markets in Hong Kong in 1997. None of the Korean AIVs had multiple basic amino acids at the HA cleavage site that confer high pathogenicity to some H5 and H7 AIVs. Phylogenetic analysis of the nucleoprotein and matrix gene demonstrated that Korean isolates cluster with Eurasian origin AIVs. The pathogenic potential of one of the isolates (MS96) was assessed after several passages in 14-day-old embryonated chicken eggs (ECE). Fourteen-day-old ECE derivatives of MS96 showed increased HA titer and embryo mortality in eggs; this was apparent after the third passage in 14-day-old ECE. Sequence analysis of the cleavage site of MS96 after the third and tenth passages in 14-day-old ECE revealed no changes in the amino acid sequence. The pathogenicity of MS96 after the tenth passage in 14-day-old eggs (MS96p10(ECE14)) was tested with 4-wk-old specific-pathogen-free chickens. The 14-day-old derivative, MS96p10(ECE14), showed wider tissue tropism and induced more severe clinical signs than the parent virus. Furthermore, after intranasal inoculation of 86-wk-old broiler breeders and 30-wk-old layers, the MS96p10(ECE14) derivative induced more severe signs of depression than the parent virus as well as a transient drop in egg production.

            Descriptors:  chick embryo virology, fowl plague physiopathology, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, avian pathogenicity, amino acid sequence, Asia, chickens, disease progression, genes, structural, viral, avian classification, Korea, molecular sequence data, phylogeny, reverse transcriptase polymerase chain reaction, sequence alignment, specific pathogen free organisms, virulence genetics.

Lee, C.W. and D.L. Suarez (2004). Application of real-time RT-PCR for the quantitation and competitive replication study of H5 and H7 subtype avian influenza virus. Journal of Virological Methods 119(2): 151-8.  ISSN: 0166-0934.

            NAL Call Number:  QR355.J6

            Abstract:  Avian influenza (AI) viruses are endemic in wild birds and if transmitted to poultry can cause serious economic losses. In the study of AI, the quantitation of virus shed from infected birds is valuable in pathogenesis studies and to determine the effectiveness of vaccines, and is performed routinely by cultivation of virus containing samples using embryonating chicken eggs (ECE) and expressed by 50% egg infectious dose (EID(50)). Although, this assay is accurate and is the standard test for infectious virus titration, the method is laborious, requires a large number of ECE, and takes at least 7 days to determine results. In this study, a one-tube hydrolysis fluorescent probe based real-time RT-PCR (RRT-PCR) was applied for the quantitation of AI virus and compared with conventional virus titration method. A strong positive correlation was observed between the amount of RNA determined by quantitative RRT-PCR and the EID(50)s determined by conventional methods. This RRT-PCR test was further applied in the study of competitive replication of co-infected H5 and H7 subtype viruses in chickens. Using hemagglutinin subtype specific probes, we were able to determine the amount of individual subtype virus, which could not have easily been done with conventional methods. This RRT-PCR based quantitation of AI virus, which is specific, sensitive, easy to perform, and rapid, will be useful for virological, pathogenesis, and protection studies.

            Descriptors:  influenza A virus, avian physiology, avian classification, avian genetics, avian isolation and purification, poultry, sensitivity and specificity, poultry diseases virology, reverse transcriptase polymerase chain reaction methods, virus replication, fluorescent dyes, hemagglutinin glycoproteins, influenza virus analysis.

Leneva, I.A., S.I.A. Mel'nikov, A.V. Mikheeva, and I.U.Z. Gendon (1985). Vzaimodeistvie belka M virusa chumy ptits dikogo tipa i ts-mutanta s ribonukleoproteidom virusa chumy ptits in vitro. [Interaction of the M protein of the wild-type fowl pest virus and its ts-mutant with the ribonucleoprotein of the fowl pest virus in vitro]. Voprosy Virusologii 30(6): 711-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The extent of inhibition of transcription realized in vitro by fowl plague virus (FPV) ribonucleoprotein (RNP) upon the addition of M protein isolated from FPV virions does not depend on nonionic detergent concentration in the reaction medium but does depend greatly on NaCl concentration. The highest inhibition of transcription is observed at a low ionic strength (0.02 M NaCl); inhibition is completely eliminated by increasing NaCl concentration to 0.3 M. When M protein isolated from FPV virions with ts mutation of M protein is added to RNP, addition to the system of 0.3 M NaCl decreases transcription inhibition but does not eliminate it completely.

            Descriptors:  influenza A virus avian metabolism, mutation, ribonucleoproteins metabolism, viral proteins metabolism, DNA directed RNA polymerases metabolism, detergents pharmacology,  dose response relationship, drug, drug interactions, avian drug effects, polyethylene glycols pharmacology, ribonucleoproteins antagonists and inhibitors, sodium chloride pharmacology, transcription, genetic drug effects, viral matrix proteins.

Leneva, I.A., A.V. Mikhejeva, V.P. Kuznetsov, W. Seidel, and Y.U.Z. Ghendon (1985). Studies of proteins soluble in acidic chloroform-methanol isolated from crude human leukocyte interferon preparations. Acta Virologica 29(6): 475-81.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Acidic chloroform-methanol soluble proteins possessing hydrophobic properties and capable of inhibiting in vitro transcriptase activity of influenza virus RNP were detected in native and partially purified human leukocyte interferon (IFN) preparations. Purification of IFN resulted in the removal of at least a portion of such proteins; however, no proteins have been found in highly-purified IFN preparations.

            Descriptors:  interferon type I analysis, proteins isolation and purification, chloroform, cytopathogenic effect, viral, DNA directed RNA polymerases antagonists and inhibitors, hydrogen-ion concentration, influenza A virus avian enzymology, interferon type I isolation and purification, methanol, proteins analysis, proteins pharmacology, ribonucleoproteins metabolism, solubility.

Lesnik, F. and O.J. Vrtiak (1973). Comparative study of fowl plague virus infected and non-infected allantoic fluid of chick embryos. Acta Veterinaria Academiae Scientiarum Hungaricae 23(2): 137-44.  ISSN: 0001-7205.

            Descriptors:  body fluids analysis, influenza A virus avian metabolism, viral proteins biosynthesis, body fluids metabolism, chick embryo, viral proteins analysis.

Li, S., M.L. Perdue, and E. Patzer (2002). Seed viruses containing novel avian HA and NA antigens for prevention against potential influenza pandemic. Developments in Biologicals 110: 135-41.  ISSN: 1424-6074.

            NAL Call Number:  QR180.3.D4

            Abstract:  An influenza pandemic could arise unexpectedly with rapid spread across the world. The efficiency of production of a vaccine and the ability to administer it widely will be among the most important factors in the ability to protect public health. The current process for producing inactivated or live attenuated influenza vaccines requires six to nine months. That reduces considerably the likelihood that the vaccine will be available during the first wave of the pandemic. Therefore, a key element of preparedness is to optimize the production process and to reduce the vaccine development time. During the 1997 H5N1 outbreak in Hong Kong, seed viruses were prepared for production of inactivated and live-attenuated vaccines. We used the cold-adapted A/Ann Arbor/6/60 as the donor virus to generate live attenuated vaccines containing genetically modified HA and NA genes from H5N1 influenza viruses. These reassortants were shown to be safe and protective in animal models. This study indicates that production of live attenuated avian influenza vaccines is feasible and that development of a library of reassortants containing different subtype HA and NA genes may reduce the vaccine preparation time for future influenza pandemics.

            Descriptors:  antigens, viral immunology, influenza prevention and control, influenza A virus avian immunology, influenza epidemiology, influenza vaccine administration and dosage.

Liao Ming, Luo KaiJian, Chen JuYi, Yao Xuan, Su XiangWen, LiLin  , and Xin ChaoAn (2004). Dynamic changes on shedding virus of experimental infection of chickens with avian influenza virus H5N1 subtype. Chinese Journal of Zoonoses 20(9): 751-753.  ISSN: 1002-2694.

            Descriptors:  tissue distribution, brain, kidneys, liver, muscles, pancreas, spleen, avian influenza virus, fowl plague virus, experimental infection, virus shedding, chickens.

Lin, A.H. and P.M. Cannon (2002). Use of pseudotyped retroviral vectors to analyze the receptor-binding pocket of hemagglutinin from a pathogenic avian influenza A virus (H7 subtype). Virus Research 83(1-2): 43-56.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The hemagglutinin (HA) protein of influenza virus binds to terminal sialic acid residues present on cell surface glycoproteins and glycolipids. The specific amino acids involved in this interaction have been identified for a H3 subtype HA from the human non-pathogenic virus, A/Aichi/2/68, by both crystallographic and mutagenesis studies. We were interested to examine the receptor-binding pocket of a H7 subtype protein from the avian pathogenic virus A/FPV/Rostock/34. Accordingly, we made amino acid substitutions at six conserved residues (Y88, T126, H174, E181, L185, and G219), suggested by comparison with the receptor-binding pocket of the H3 protein, and analyzed the resulting proteins using pseudotyped retroviral vectors. The use of these vectors enabled us to quantitate both the ability of the mutant HA proteins to bind with receptor-expressing cells, and also to promote virus-cell fusion by measuring vector titer. Using this system, we identified a subset of mutants with impaired receptor-binding activity and a corresponding decrease in titer, but which retained the ability to induce syncytia in low pH cell-cell fusion assays. The most severely affected mutants contained more than one substitution, with the triple mutant Y88F/E181Q/G219K being the most defective. These observations highlight the importance of multiple contact points for the interaction between sialic acid and HA.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, receptors, virus metabolism, 3T3 cells, amino acid sequence, amino acid substitution, binding sites, cell line, transformed, cell membrane metabolism, gene expression, genetic vectors, giant cells, hemagglutinin glycoproteins, influenza virus chemistry, hydrogen-ion concentration, avian metabolism, avian pathogenicity, avian physiology, membrane fusion, mice, molecular sequence data, mutagenesis, protein structure, tertiary, receptors, virus chemistry, retroviridae, sequence homology, amino acid, sialic acids chemistry, sialic acids metabolism, temperature.

Linitskaia, G.L., A.A. Iatsyna, N.L. Pushkarskaia, and G.A. Galegov (1978). Vliianie ribovirina (1-beta-D-ribofuranozil-1,2,4-triazol-3-karboksimida) na induktsiuu RNK-zavisimoi RNK-polimerazy i obrazovanie virusspetsificheskikh polisom v kul'ture kletok, infitsirovannykh virusom grippa A. [Effect of ribovirine (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboximide) on RNA-dependent RNA-polymerase induction and virus-specific polysome formation in cell cultures infected with influenza A virus]. Voprosy Meditsinskoi Khimii 24(5): 699-702.  ISSN: 0042-8809.

            Descriptors:  antiviral agents pharmacology, influenza A virus avian drug effects, polyribosomes drug effects, RNA nucleotidyltransferases metabolism, RNA replicase metabolism, ribavirin pharmacology, ribonucleosides pharmacology, virus replication drug effects, cultured cells, chick embryo, depression, chemical, enzyme induction drug effects, RNA viral biosynthesis, viral proteins biosynthesis.

Liozner, A.L., G.K. Vorkunova, N.A. Volynskaia, and A.G. Bukrinskaia (1983). Antigennye kharakteristiki belka M virusa grippa. Vyiavlenie metodom ELISA razlichii belkov M chuvstvitel'nogo i ustoichivogo k remantadinu variantov virusa. [Antigenic characteristics of influenza virus protein M. The ELISA detection of the differences in the M proteins of remantadine-sensitive and -resistant variants of the virus]. Voprosy Virusologii (3): 281-6.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Antigenic characteristics of influenza A virus M protein were studied by ELISA using a monospecific antiserum to M protein and monoclonal antibodies to the B4 and A7 antigenic determinants of M protein. The design of the test systems for M protein detection was based on the indirect and "sandwich" variants of ELISA as well as on the previously developed principle of blocking the indirect reaction. The latter variant of the test system had the highest specificity: 0.1--0.5 ng of specific protein. The high specificity of the method allows subtle antigenic differences of M protein within influenza A virus group to be detected. Comparative studies of remantadine-sensitive and resistant variants of the classic fowl plague virus showed the previously demonstrated significant differences in the physico-chemical properties of M protein of these variants to correlate with a marked antigenic divergence associated, in particular, with greater antigenicity of B4 epitope in M protein of remantadine-sensitive strains. The test system of ELISA blocking was found to be useful for M protein detection in virus-containing materials not subjected to purification and concentration (native allantoic fluids). The latter attests to the expedience of using ELISA in clinical diagnostic studies of influenza.

            Descriptors:  adamantane analogs and derivatives, antigens, viral analysis, glycoproteins analysis, influenza A virus analysis, rimantadine pharmacology, viral proteins analysis, enzyme linked immunosorbent assay, glycoproteins immunology, influenza A virus avian analysis, avian drug effects, avian immunology, influenza A virus drug effects, influenza A virus immunology, viral proteins immunology.

Lipatov, A.S., A.K. Gitel'man, E.A. Govorkova, and I.U.A. Smirnov (1995). Izmeneniia biologicheskikh i fiziko-khimicheskikh svoistv gemaggliutinina H2 ptich'ego virusa grippa A v protsesse adaptatsii k novomu khozainu. [Changes in biological and physico-chemical properties of avian influenza virus A hemagglutinin H2 during adaptation to a new host]. Voprosy Virusologii 40(5): 208-11.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Avian influenza A virus with H2 hemagglutinin has been adapted to mice for the first time. Alterations in the hemagglutinin of adapted variants of the virus as a result of adaptation to a new host are described. Hemagglutinin of a highly virulent adapted variant differed from the parental avirulent strain by antigenic structure, electrophoretic mobility, and receptor activity during interactions with murine red cells.

            Descriptors:  adaptation, physiological, hemagglutinins viral metabolism, influenza A virus avian physiology, cultured cells, chick embryo, dogs, erythrocytes virology, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral chemistry, avian metabolism, avian pathogenicity, lethal dose 50, mice.

Lipatov, A.S., A.K. Gitelman, and Y.U.A. Smirnov (1997). Prevention and treatment of lethal influenza A virus bronchopneumonia in mice by monoclonal antibody against haemagglutinin stem region. Acta Virologica 41(6): 337-40.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The protective properties of monoclonal antibody (MoAb) C179 directed to the stem region of haemagglutinin (HA) H2 that possessed fusion-inhibition and unique broad cross-neutralizing activities were examined in a mouse model. The MoAb efficiently protected mice against a lethal challenge with pneumovirulent human (H1) and avian (H2) strains of influenza A virus. Survival rates in mice that received intraperitonealy (i.p.) 1000 micrograms of the MoAb per mouse a day before the virus challenge were 90% for H1 and 100% for H2 strain. The dose of the MoAb of 100 micrograms per mouse significantly decreased mortality in mice. Moreover, the MoAb was also efficient in treatment of lethal bronhopneumonia caused by H2 influenza virus. The survival rate in mice that received 1000 micrograms of the MoAb per mouse 2 days after the virus challenge was 90%, while that in the control group was 30% only. These results indicate that the MoAb was effective in protection of animals against lethal influenza A infection without significant difference between H1 and H2 subtypes. The MoAb exerted significant effect in treatment of mice infected with H2 influenza virus. Thus, these data allow to suggest that the stem region of HA might be a potential target for prevention of influenza virus infection and antiviral therapy.

            Descriptors:  antibodies, monoclonal therapeutic use, bronchopneumonia therapy, hemagglutinins viral immunology, influenza therapy, influenza A virus avian immunology, human immunology, pneumonia, viral therapy, antibodies, monoclonal immunology, bronchopneumonia prevention and control, dose response relationship, immunologic, influenza prevention and control, mice, pneumonia, viral prevention and control, random allocation, time factors.

Lipkind, M., K. Hornstein, E. Shihmanter, K. Davidov, and D. Shoham (1983). Retrospective identification as influenza virus of a hemagglutinating agent isolated from turkeys in Israel in 1973. Comparative Immunology, Microbiology and Infectious Diseases 6(2): 135-9.  ISSN: 0147-9571.

            NAL Call Number:  QR180.C62

            Descriptors:  hemagglutinins viral isolation and purification, influenza A virus avian isolation and purification, turkeys microbiology, hemagglutinins viral immunology, avian immunology, Israel.

Lipkind, M., I.V. Tsvetkova, and N.V. Gribkova ( 1973). Neuraminidase and hemagglutinin activities in subcellular fractions of NDV- and FPV-infected chick embryo cells and their re-distribution following Triton X 100 treatment.  Archiv Fur Die Gesamte Virusforschung  40(3): 300-6.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  hemagglutinins viral analysis, influenza A virus avian immunology, neuraminidase analysis, Newcastle disease virus immunology, surface active agents pharmacology, cell fractionation, cell nucleus, cultured cells, centrifugation, density gradient, chick embryo, avian enzymology, avian growth and development, microsomes, mitochondria, Newcastle disease virus enzymology, Newcastle disease virus growth and development, ribosomes, subcellular fractions analysis.

Lipkind, M., Y. Weisman, and E. Shihmanter (1987). The isolation of influenza virus from chickens in Israel and studies on its antigenic relationships with other native isolates of the same antigenicity by means of monoclonal antibodies. Comparative Immunology, Microbiology and Infectious Diseases 10(2): 133-9.  ISSN: 0147-9571.

            NAL Call Number:  QR180.C62

            Abstract:  A hemagglutinating (HA) agent isolated from an outbreak of a respiratory disease in a kibbutz broiler farm was identified as influenza virus A/chicken/Degania, Israel/80(H7N2). Investigation using a panel of 5 monoclonal antibodies against H7 antigenic subtype has shown substantial difference of the isolate from the other H7-containing influenza viruses isolated in Israel. Antigenic relationships between the native H7-containing strains revealed by means of the monoclonal antibodies led to re-evaluation of the suggested views on local epizootiology and interspecies transfer of avian influenza.

            Descriptors:  antigens, viral analysis, chickens, fowl plague microbiology, influenza A virus avian immunology, antibodies, monoclonal immunology, chick embryo, hemagglutination inhibition tests, avian isolation and purification, Israel.

Lipkind, M.A., I.V. Tsvetkova, and V.N. Muraviyov (1977). Animal influenza virus neuraminidase: studies on dependence of some of its properties on its association with hemagglutinin. Developments in Biological Standardization 39: 447-52.  ISSN: 0301-5149.

            NAL Call Number:  QR180.3.D4

            Abstract:  Neuraminidase (Nase) thermostability and sensitivity to pH treatment as well as specific enzymatic activity (Nase activity per 1 HA unit) were determined in two groups of animal influenza virus strains containing equine 1 and equine 2 Nase subtypes, respectively (A/equine/Prague/56 (Heq1 Neq1), A/equine/Cambridge/63 (Heq1 Neq1), A/FPV/Dutch/34 (Hav1 Neq1), A/chicken/Germany "N" (Hav2 Neq1), in one group, and A/equine/Miami/1/63 (Heq2 Neq2), A/turkey/Canada/63 (Hav6 Neq2), A/duck/Ukraine/1/63 (Hav7 Neq2), in the other group). Nase of all the strains used was thermotabile when heated at pH 4.5. Nase of Neq1 subtype irrespective of strain containing it was thermolabilt when heated both at pH 6.5 and 8.1 and sensitive to pH 4.5 treatment as such (without heating). Inversely, Nase of Neq2 antigenic subtype irrespective of the strain containing it, was thermostable when heated at pH 6.5 AND 8.1 and resistant to the treatment of pH 4.5. Specific enzymatic activity was considerably higher in all the strains containing Neq2 as compared to Neq1-containing strains (4-6 times as much). The results suggest that thermostability and pH sensitivity of equine Nases of both antigenic subtypes, as well as their specific activities, do not depend on the sort of HA which is coupled with enzyme subunits at viral envelope, but attributed rather to properties of the subunits themselves, such as glycoprotein entities. The data concerning specific activities may suggest that in the case of various combinations of Nase subunits with different HA subunits the amount of enzyme per virion is of the same order.

            Descriptors:  influenza A virus immunology, neuraminidase immunology, antigens, viral, heat, hemagglutinins viral, hydrogen-ion concentration, influenza A virus avian immunology, influenza A virus enzymology, influenza A virus genetics, recombination, genetic.

Lipkind, M. and E. Shihmanter (1995). Antigenic heterogeneity of N2 neuraminidases of avian influenza viruses isolated in Israel. Comparative Immunology Microbiology and Infectious Diseases 18(1): 55-68.  ISSN: 0147-9571.

            NAL Call Number:  QR180.C62

            Abstract:  Twenty one N2 neuraminidase (NA)-containing viruses isolated in Israel from different avian hosts during 1971-1984 were studied comparatively by means of the panel of 7 monoclonal antibodies (MAB) against A/Guiyang/57(H2N2) virus. Fifteen from the 21 viruses were studied in comprehensive cross reaction NA inhibition (NI) tests with the corresponding polyclonal antisera. The principal result of the studies is that all the isolates can be distributed into two main groups. The 1st group includes the majority of the isolates whose NA shows close relatedness to the "early" (1957 type) N2 NA by NI tests with polyclonal antisera, and demonstrates remarkable stability in the NI tests by reacting with the same 6 from 7 MABs of the panel. The 2nd group does not show any special kinship to either "early" or "late" (1968 type) N2 when analyzed with polyclonal antisera and demonstrates heterogeneity by the analysis with the MABs. A hypothetical explanation of the phenomenon of co-circulation in the local avian reservoir of viral strains displaying either remarkable stability or wide heterogeneity of their NAs is suggested. In accordance with it, the viruses with "stable" ("conservative") N2 NA did not leave the avian reservoir and, hence, did not drift because of very low antibody "selection pressure". Contrary to it, the viruses with heterogeneous N2 NA had been circulating in the human (mammalian) reservoir during various periods before their transfer into the avian reservoir; they drifted accordingly and, being then isolated from birds and designated as "avian" viruses, demonstrate heterogeneity of their NAs which is typical for human viruses.

            Descriptors:  enzymology, immune system, infection, microbiology, nervous system, veterinary medicine, antigenicity viral ecology.

Lisovskaya, K.V., L.M. Garmashova, and T.E. Medvedeva (1981). Analysis of ts mutations of cold-adapted influenza A/Leningrad/134/57 virus variants. Acta Virologica 25(6): 415-7.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  By recombination of ts mutants of fowl plague virus belonging to different complementation groups with two cold-adapted variants of human influenza virus, the number and gene localization of ts mutations occurring in these variants was determined. In the course of passaging of human influenza virus at lowered temperature, the number of genes with ts mutations increased.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, cold, genetic complementation test, mutation, recombination, genetic.

Litvinov, A.N. (1967). Vliianie interferona na dinamiku obrazovaniia antitel u kur pri psevdochume ptits. [Effect of interferon on the dynamics of antibody formation in chickens in avian pseudopest].  Antibiotiki 12(7): 602-4.  ISSN: 0003-5637.

            NAL Call Number:  396.8 An84

            Descriptors:  antibody formation drug effects, interferons pharmacology, orthomyxoviridae infections immunology, poultry diseases immunology, chick embryo, hemagglutination inhibition tests, influenza A virus avian immunology.

Liu, H., J. Cheng, D. Peng,  L. Jia, R. Zhang, and X. Liu (2002). [Comparison of sequences of the hemagglutinin gene and phylogenetical analysis of H9 subtype avian influenza viruses isolated from some regions in China]. Weishengwu Xuebao 42(3): 288-97.  ISSN: 0001-6209.

            NAL Call Number:  448.3 Ac83

            Abstract:  In order to explore the genetic mutaions of the hemagglutinin(HA) gene and the law of molecular epidemiology of H9 subtype avian influenza viruses in China, 23 H9 subtype avian influenza viruses(AIVs) were isolated from 12 provinces of China in recent years. Their nucleotide sequences of cDNA of HA gene were determined by RT-PCR and sequencing. Their nucleotide and putaive amino acid sequences homology was compared. The results showed that their nucleotide sequence homology was from 94.1% to 100% and that amino acid sequence homology was 95.4% to 100%. The sequences of the HA gene of these isolates were analyzed and compared with that of another 8 isolates from reference. The similedty indicated that HK170499 isolated from Hong Kong was close to the 2 isolates of Japan. And of the 31 isolates with complete HA gene sequences there were 5 isolates, HA gene of which were loss of one potelltial glycosylation site, which were CKGS199, CKTJ196, CKT296, CKSH300 and CKBJ197. Then 1098 nucleotide regions (bases 55 to 1,152) of HA gene of 23 isolates in this study were analyzed phylogenetically and compared with sequences from 31 H9 subtype viruses available in the GenBank database. Although considerable variation at the cleavage sites of the different viruses was observed, giving 10 different amino acid motits, none had multiple basic amino acids that correlate with highly pathogenic avian influenza (HPAI) isolates. Examination of amino acid sequences involved in repeptor binding site(RBS) revealed that the amino acid residue at position 191 characteristically distributed in the 54 isolates, that is, this amino acid residue of the isolates of mainland China and several Hong Kong strains was Asn(N) and that of the others was His(H). And the 141 143 amino acid residues, involved in forming the potential glycosylation sites, had the similary characteristic distribution with the 191aa position. The isolates with Asn-191. excluding CKBJ197, had NVS in the position 141aa143aa, meanwhile those with His-191 had NVT. Twenty-six mainland China isolates was genetically in Eurasian lineage but did not show distinctly geographical and temporal relationship. It is concluded that in recent years H9N2 subtype AIV, circulating in chicken flocks of mainland China, may have a common origini. These findings provides importan basis for establishment of scientifically preventive measurements to control H9 subtype avian influenza.

            Descriptors:  genes viral, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, phylogeny, amino acid sequence, base sequence, chickens, China, DNA, complementary genetics, fowl plague virology, avian classification, avian isolation and purification, sequence homology.

Liu HongQi, Huang Yong, Cheng Jian, Peng DaXin, Jia LiJun, Zhang RuKuan, and Liu XiuFan (2002). Genetic mutations of the hemagglutinin gene of H9N2 subtype avian influenza viruses under the selective pressure of vaccination. Chinese Journal of Virology 18(2): 149-154.  ISSN: 1000-8721.

            Descriptors:  vaccination, avian influenza virus, genetic mutations, poultry.

Liu, H., X. Liu, J. Cheng, D. Peng, L. Jia, and Y. Huang (2003). Phylogenetic analysis of the hemagglutinin genes of twenty-six avian influenza viruses of subtype H9N2 isolated from chickens in China during 1996-2001. Avian Diseases 47(1): 116-127.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The complete coding region of hemagglutinin genes from 26 influenza A viruses of H9N2 subtype isolated Prom chicken flocks in China during 1996-2001 was amplified and sequenced. Sequence analysis and phylogenetic studies of H9N2 subtype viruses on the basis of data of 26 viruses in this study and 71 selected strains available in the GenBank were conducted. The results revealed that all the mainland China isolates showed high homology (94.1%-100%) and were assigned to a special sublineage in the major Eurasian lineage, in contrast to the high heterogeneity of Hong Kong SAR isolates. All the 29 mainland China isolates and six Hong Kong SAR strains also had the following common characteristics: sharing the same sequence of proteolytic cleavage site with one additional basic amino acid, RSSR, with only two exceptions; having the same amino acid motif of the receptor-binding site, YWTNV/ALY; 23 of 28 isolates bearing seven potential glycosylation sites and the remaining five having six; and sharing characteristic deduced amino acid residues Asn-183 at the receptor-binding site and Ser-130 at the potential glycosylation site. We concluded that the H9N2 subtype influenza viruses circulating in chicken flocks in China since the 1990s and Ck/HK/G9/97-like viruses isolated in Hong Kong SAR should have a common origin, whereas Qu/HK/G1/97-like viruses including human strains isolated in Hong Kong SAR might originate from other places. The available evidence also suggests that the H9N2 viruses of special lineage themselves and factors prone to secondary infections may contribute to the widespread and dominant distribution of viruses of this subtype in chicken flocks in China and other Asian countries.

            Descriptors:  infection, molecular genetics, systematics and taxonomy, virology, phylogenetic analysis mathematical and computer techniques, reverse transcriptase polymerase chain reaction, genetic techniques, laboratory techniques, sequence analysis, sequence homology.

Liu, J.H., K. Okazaki, W.M. Shi, and H. Kida (2003). Phylogenetic analysis of hemagglutinin and neuraminidase genes of H9N2 viruses isolated from migratory ducks. Virus Genes 27(3): 291-6.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  Genetic analysis indicated that the pandemic influenza strains derived from wild aquatic birds harbor viruses of 15 hemagglutinin (HA) and 9 neuraminidase (NA) antigenic subtypes. Surveillance studies have shown that H9N2 subtype viruses are worldwide in domestic poultry and could infect mammalian species, including humans. Here, we genetically analyzed the HA and NA genes of five H9N2 viruses isolated from the migratory ducks in Hokkaido, Japan, the flyway of migration from Siberia during 1997-2000. The results showed that HA and NA genes of these viruses belong to the same lineages, respectively. Compared with those of A/quail/Hong Kong/G1/97-like and A/duck/Hong Kong/Y280/97-like viruses, HA and NA of the migratory duck isolates had a close relationship with those of H9N2 viruses isolated from the chicken in Korea, indicating that the Korea H9N2 viruses might be derived from the migratory ducks. The NA genes of the five isolates were located in the same cluster as those of N2 viruses, which had caused a human pandemic in 1968, indicating that the NA genes of the previous pandemic strains are still circulating in waterfowl reservoirs. The present results further emphasize the importance of carrying out molecular epidemiological surveillance of H9N2 viruses in wild ducks to obtain more information for the future human influenza pandemics preparedness.

            Descriptors:  ducks virology, influenza A virus avian genetics, amino acid sequence, base sequence,  binding sites genetics, DNA, viral genetics, disease reservoirs, epidemiology, molecular, genes viral, hemagglutinins viral genetics, avian enzymology, avian immunology, avian isolation and purification, Japan, neuraminidase genetics, phylogeny.

Liu, J.H., Q.M. Wu, W.M. Shi, and Y.P. Guo (2003). Cloning and expression of the nonstructural protein (NS1) of the H9N2 chicken influenza virus. Virologica Sinica 18(5): 503-505.  ISSN: 1003-5125.

            NAL Call Number:  QR355.P5

            Descriptors:  Western blot, cloning, influenza virus.

Liu, J.H., K. Okazaki, G.R. Bai, W.M. Shi, A. Mweene, and H. Kida (2004). Interregional transmission of the internal protein genes of H2 influenza virus in migratory ducks from North America to Eurasia. Virus Genes  29(1): 81-6.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  H2 influenza virus caused a pandemic in 1957 and has the possibility to cause outbreaks in the future. To assess the evolutionary characteristics of H2 influenza viruses isolated from migratory ducks that congregate in Hokkaido, Japan, on their flyway of migration from Siberia in 2001, we investigated the phylogenetic relationships among these viruses and avian and human viruses described previously. Phylogenetic analysis showed that the PB2 gene of Dk/Hokkaido/107/01 (H2N3) and the PA gene of Dk/Hokkaido/95/01 (H2N2) belonged to the American lineage of avian virus and that the other genes of the isolates belonged to the Eurasian lineage. These results indicate that the internal protein genes might be transmitted from American to Eurasian avian host. Thus, it is further confirmed that interregional transmission of influenza viruses occurred between the North American and Eurasian birds. The fact that reassortants could be generated in the migratory ducks between North American and Eurasian avian virus lineage further stresses the importance of global surveillance among the migratory ducks.

            Descriptors:  ducks virology, emigration and immigration, influenza A virus, avian genetics, influenza, avian virology, viral proteins genetics, Asia, Europe, avian influenza A virus classification, molecular sequence data, North America, phylogeny, sequence analysis, DNA.

Lohmann, W. (1976). A possible mechanism for the action of some myxoviruses. Radiation and Environmental Biophysics 13(4): 273-80.  ISSN: 0301-634X.

            NAL Call Number:  442.8 B5242

            Abstract:  The redox properties of some myxoviruses [Fowl plaque virus strain Rostock (FPV), New Castle Disease virus strain Italy (NDV), B/Hong Kong, A/Port Chalmers, A/Victoria, A/Scotland, and A/Fort Dir) and electron microscopic studies as well as by the determination of the hemagglutination (HA) titer (antigen efficiency). The results have shown that viruses decrease the spin concentration of Cu2+ by acting as a reducing species (electron donor) which will result in the inactivation (oxidation) of the virus. Addition of an oxidizing substance, such as H2O2, to a virus suspension also leads to an oxidation of the viruses, and, thus, to their inability to reduce Cu2+. This result is confirmed by the decrease of the HA titer of viruses with increasing Cu2+ concentrations. H2O2 could not be applied for the HA titer test since it interacts with the erythrocytes of the chicken blood used for this determination. Therefore, another oxidizing substance (oxidized glutathione, GSS) was selected which exhibited a slightly less pronounced effect than Cu2+. Since reduced glutathione (GSH) exerts a similar but less pronounced effect than GSS, it might be concluded that viruses have a redox system of their own and act as reducing or oxidizing substance depending on the biological receptor system. Electron microscopic studies confirm this hypothesis. As can be seen by the electron micrographs, increasing concentrations of either Cu2+, GSS, H2O2, KMnO4, or GSH will, finally, result in a complete destruction of the virus. Because of structural similarities it might be assumed that other types of viruses behave very similarly.

            Descriptors:  influenza A virus metabolism, Newcastle disease virus metabolism, copper, electron spin resonance spectroscopy, glutathione, hemagglutination, viral, avian metabolism, avian ultrastructure, human metabolism, human ultrastructure, Newcastle disease virus ultrastructure, oxidation reduction, peroxides, potassium permanganate, time factors.

Lohmeyer, J. and H.D. Klenk (1979). A mutant of influenza virus with a temperature-sensitive defect in the posttranslational processing of the hemagglutinin. Virology 93(1): 134-45.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  endoplasmic reticulum metabolism, hemagglutinins viral immunology, influenza A virus avian metabolism, viral proteins metabolism, carbohydrates metabolism, cell line, hemagglutination, viral, avian genetics, mutation, neuraminidase metabolism, temperature.

Lohmeyer, J., L.T. Talens, and H.D. Klenk (1979). Biosynthesis of the influenza virus envelope in abortive infection. Journal of General Virology 42(1): 73-88.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Synthesis and processing of the envelope proteins of influenza A virus (fowl plague virus) have been analysed in BHK, HeLa and L cells, in which the virus undergoes abortive replication and does not form virus particles, and in the productive chick embryo fibroblast system. In abortive infection, synthesis of the M protein is specifically inhibited. The extent of this defect varies depending on the host cell and the amount of virus particles formed closely reflects the amount of M synthesized. Cell fractionation experiments demonstrated that the haemagglutinin glycoprotein HA is synthesized in abortive as well as in productive cells at the rough endoplasmic reticulum, that it migrates via smooth internal membranes to the plasma membrane and that it is cleaved by proteolysis into fragments HA1 and HA2 in the course of migration. Immune electron  microscopy using monospecific antibodies against haemagglutinin and neuraminidase showed that both glycoproteins are exposed at the cell surface. Thus, synthesis and processing of the virus glycoproteins does not depend on the formation of the M protein. However, the M protein appears to be necessary for budding and thus for particle formation.

            Descriptors:  influenza A virus avian growth and development, viral proteins biosynthesis, cell line, cell membrane analysis, cultured cells, endoplasmic reticulum metabolism, glycoproteins biosynthesis, hemagglutinins viral analysis, neuraminidase biosynthesis, viral proteins analysis.

Lomniczi, B., F.X. Bosch, A.J. Hay, and J.J. Skehel (1977). Influenza virus infection of a cell-cycle mutant of Chinese hamster ovary cells. Journal of General Virology 35(1): 187-90.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  cell line, influenza A virus avian growth and development, mutation, cell division, DNA biosynthesis, hamsters, avian metabolism, ovary, peptide synthesis, temperature, viral proteins biosynthesis, virus replication.

Long, W. and D.C. Burke (1968). The effect of infection with fowl-plague virus on protein synthesis in chick-embryo cells. Biochemical Journal  110(3): 41.  ISSN: 0264-6021.

            NAL Call Number:  QP501,B64

            Descriptors:  chick embryo metabolism, influenza A virus avian metabolism, avian radiation effects, orthomyxoviridae infections metabolism, proteins biosynthesis, depression, chemical, interferons biosynthesis, RNA viral biosynthesis, ultraviolet rays, viral proteins biosynthesis, virus replication drug effects.

Long, W.F. (1971). Effect of metabolic inhibitors on viral and polynucleotide induction of chick cell interferon. Microbios  4(15): 253-9.  ISSN: 0026-2633.

            NAL Call Number:  QR1.M54

            Descriptors:  cycloheximide pharmacology, dactinomycin pharmacology, influenza A virus avian radiation effects, interferons biosynthesis, poly I C pharmacology, puromycin pharmacology,  reoviridae, chick embryo, radiation effects, tissue culture, ultraviolet rays.

Long, W.F. and D.C. Burke (1970). The effect of infection with fowl plague virus on protein synthesis in chick embryo cells. Journal of General Virology 6(1): 1-14.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian metabolism, proteins biosynthesis, carbon isotopes, chick embryo, cycloheximide pharmacology, dactinomycin pharmacology, avian drug effects, avian radiation effects, interferons pharmacology, phenylalanine pharmacology, puromycin pharmacology, RNA biosynthesis, RNA viral biosynthesis, radiation effects, time factors, tritium, ultraviolet rays, uridine metabolism, valine metabolism, virus cultivation.

Long, W.F. and J. Olusanya (1972). Adamantanamine and early events following influenza virus infection. Archiv Fur Die Gesamte Virusforschung 36(1): 18-22.  ISSN: 0003-9012.

            NAL Call Number:  448.3 Ar23

            Descriptors:  amantadine pharmacology, influenza A virus avian drug effects, RNA viral antagonists and inhibitors, carbon isotopes, cultured cells drug effects, cultured cells metabolism, chick embryo, cycloheximide pharmacology, dactinomycin pharmacology, depression, chemical, electrophoresis, disc, avian growth and development, avian metabolism, avian radiation effects, interferons biosynthesis, proteins biosynthesis, RNA analysis, RNA biosynthesis, viral biosynthesis, radiation effects, time factors, tritium, ultraviolet rays, uridine metabolism, virus replication drug effects.

Lu, B.L., R.G. Webster, and V.S. Hinshaw (1982). Failure to detect hemagglutination-inhibiting antibodies with intact avian influenza virions. Infection and Immunity 38(2): 530-5.  ISSN: 0019-9567.

            NAL Call Number:  QR1.I57

            Descriptors:  antibodies, viral analysis, hemagglutinins viral immunology, influenza A virus avian immunology, orthomyxoviridae infections immunology, ducks immunology, ferrets immunology, hemagglutination inhibition tests, avian physiology, mice, mice inbred BALB c immunology, T lymphocytes, cytotoxic immunology, virus replication.

Lu, H. and A.E. Castro (2004). Evaluation of the infectivity, length of infection, and immune response of a low-pathogenicity H7N2 avian influenza virus in specific-pathogen-free chickens. Avian Diseases 48(2): 263-70.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The H7N2 subtype of avian influenza virus (AIV) field isolate (H7N2/chicken/PA/3779-2/97), which caused the 1997-98 AIV outbreak in Pennsylvania, was evaluated for its infectivity, length of infection, and immune response in specific-pathogen-free (SPF) chickens. The composite findings of three clinical trials with various concentrations of virus indicated that this H7N2 subtype contained minimal pathogenicity for chickens. The concentration of the virus in the inoculum proved critical in the establishment of a productive infection in a chicken. Seven-day-old SPF chickens were not infected when inoculated with 10(0.7-2.0) mean embryo lethal dose (ELD50) of the H7N2 virus per bird. At this dose level, the immune response to this virus was not detected by the hemagglutination-inhibition (HI) test. Nonetheless, chickens at ages of 5 and 23 wk old tested were successfully infected when exposed to 10(4.7-5.7) ELD50 of H7N2 infectious doses per bird by various routes of administration and also by direct contact. Infected birds started shedding virus as early as 2 days postinoculation, and the period of virus shedding occurred mostly within 1 or 2 wk postinoculation (WPI). This H7N2 subtype of AIV induced a measurable immune response in all birds within 2 wk after virus exposure. Antibody titers were associated with AIV infectious doses and age of exposure of birds. Challenge of these infected birds with the same H7N2 virus at 5 and 10 WPI indicated the infective virus was recoverable from cloacal swabs at 3 days postchallenge and disappeared thereafter. In these challenged birds, the antibody levels as measured by the HI test spiked within 1-2 wk.

            Descriptors:  antibodies, viral analysis, chickens virology, influenza A virus, avian pathogenicity, avian virology, poultry diseases virology, antibody formation, cloaca virology, hemagglutination inhibition tests methods, hemagglutination inhibition tests veterinary, immunophenotyping, avian immunology, avian isolation and purification, avian immunology, poultry diseases immunology, specific pathogen free organisms, virus shedding.

Lu, J., Peng DaXin, Wu YanTao, Zhang RuKuan, and Liu XiuFan (2003). Amplification of full-length hemagglutinin and neuraminidase genes of H9N2 avian influenza virus and gene sequence comparison. Journal of Yangzhou University, Agricultural and Life Sciences Edition, Yangzhou China 24(1): 18-22.  ISSN: 1671-4652.

            NAL Call Number:  S19.Y36

            Descriptors:  amino acid, complementary DNA, hemagglutinins, strains, avian influenza virus, China.

Lyon, J.A. and V.S. Hinshaw (1993). Inhibition of nitric oxide induction from avian macrophage cell lines by influenza virus. Avian Diseases 37(3): 868-73.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The virulent avian influenza virus A/Ty/Ont/7732/66 (H5N9) (Ty/Ont) causes a rapid destruction of lymphoid cells in infected birds. Avian macrophage cell lines, HD11 and MQ-NCSU, support productive replication of Ty/Ont and other influenza viruses. Therefore, the ability of these cell lines to produce nitric oxide (NO), a potentially cytotoxic mediator, in response to infection with Ty/Ont was examined. Although treatment with bacterial lipopolysaccharides (LPS) resulted in high NO levels, infection of macrophages with Ty/Ont resulted in NO levels lower than NO levels in untreated cells. Furthermore, Ty/Ont was able to inhibit the positive response to LPS in cultures simultaneously treated with LPS and virus. However, inactivated influenza virus did not exhibit this inhibitory effect. Different strains of influenza virus varied in their ability to inhibit NO production by the macrophages; this may be related to the level of virus replication in these cells. These data suggest that the ability of the avian macrophage to activate the NO synthesis pathway is seriously impaired by infection with virulent influenza viruses such as Ty/Ont.

            Descriptors:  influenza A virus avian pathogenicity, macrophages metabolism, macrophages microbiology, nitric oxide biosynthesis, amino acid oxidoreductases antagonists and inhibitors, arginine analogs and derivatives, arginine pharmacology, cell line, chickens, fowl plague etiology, avian physiology, macrophages immunology, mice, nitric oxide synthase,  orthomyxoviridae pathogenicity, orthomyxoviridae physiology, species specificity, virus replication, omega n methylarginine.

Lyon, J.A. and V.S. Hinshaw (1991). Replication of influenza A viruses in an avian macrophage cell line.  Journal of General Virology 72(Pt. 8): 2011-3.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The virulent avian influenza virus A/Ty/Ont/7732/66 (H5N9) (Ty/Ont) causes severe destruction of the lymphoid cells in infected birds. Previous studies have suggested that viral infection of macrophages may be involved. However, Ty/Ont failed to replicate productively in primary cultures of chicken macrophages. Therefore, in an effort to develop an in vitro system for our studies, we examined the susceptibility of an avian macrophage cell line, HD11, to Ty/Ont. We found that Ty/Ont replicated in the HD11 cells to high titres, as measured by haemagglutination (HA) assays and infectivity yields. To determine whether this property was unique to Ty/Ont, we also examined the replication of influenza viruses representative of all 13 HA subtypes and an attenuated variant of Ty/Ont. All of the tested viruses replicated in HD11 cells; the avirulent strains required the presence of trypsin in the culture medium whereas virulent viruses and the attenuated variant of Ty/Ont did not. These results suggest that the HD11 cells can support the replication of a wide variety of influenza viruses and that this continuous avian cell line may prove useful for in vitro studies on these viruses.

            Descriptors:  influenza A virus avian physiology, macrophages microbiology, virus replication, cell line, chickens.

Machavariani, A.T. (1970 ). Primenenie zhivykh vaktsin protiv psevdochumy ptits. [Use of live vaccine against fowl pseudoplague]. Veterinariia (2): 49-52.  ISSN: 0042-4846.

            NAL Call Number:  41.8 V6426

            Descriptors:  fowl plague immunology, avian influenza virus, viral vaccines, aerosols, chickens.

Madeley, C.R., W.H. Allan, and A.P. Kendal (1971). Studies with avian influenza A viruses: serological relations of the hemagglutinin and neuraminidase antigens of ten virus isolates. Journal of General Virology 12(Pt. 2): 69-78.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  avian influenza A virus, strain comparisons, hemagglutinin, neuraminidase anitgens, chickens.

Mahy, B.W., T. Barrett, D.J. Briedis, J.M. Brownson, and A.J. Wolstenholme (1980). Influence of the host cell on influenza virus replication. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 288(1029): 349-57.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  The replication of influenza virus is characterized by a unique dependence upon host cell nuclear function. In contrast to all other negative strand RNA viruses, transcription from host cellular DNA is a prerequisite for the synthesis of virus-specific messenger RNA; new DNA synthesis is not required. We have analysed the distribution of each of the nine virus-specified proteins between the nucleus and cytoplasm of virus-infected cells, and find that in addition of the NP and the NS1 proteins, two of the three P proteins show preferential migration into the nucleus. This subgroup of virus proteins may be involved in the early transcription of the viral genome which probably occurs in the nucleus. In non-permissive cell lines and in cells whose DNA function has been impaired by treatment with ultraviolet light, N-acetoxyacetaminofluorene or low doses of actinomycin D, production of some late virus proteins is inhibited. The specific host function required for this switch to late protein synthesis is unknown but in the cells treated with actinomycin D an abnormal accumulation of virus-specific mRNA occurs in the nucleus. In all cases studied, synthesis of new vRNA ceases when production of these late proteins has been blocked.

            Descriptors:  influenza A virus avian genetics, RNA viral biosynthesis, virus replication drug effects, biological transport drug effects, cell nucleus physiology, cultured cells, cytoplasm metabolism, dactinomycin pharmacology, poly A metabolism, messenger metabolism, transcription, genetic, viral proteins metabolism.

Mahy, B.W. and P.A. Bromley (1969). Synthesis of ribonuclease-resistant ribonucleic acid by fowl-plague-virus-induced ribonucleic acid polymerase. Biochemical Journal 114(4): 64.  ISSN: 0264-6021.

            NAL Call Number:  QP501,B64

            Descriptors:  influenza A virus avian, RNA biosynthesis, RNA nucleotidyltransferases metabolism, ribonucleases, chick embryo, fibroblasts metabolism, tissue culture, virus cultivation.

Mahy, B.W., N.J. Cox, S.J. Armstrong, and R.D. Barry (1973). Multiplication of influenza virus in the presence of cordycepin, an inhibitor of cellular RNA synthesis. Nature New Biology 243(127): 172-4.  ISSN: 0090-0028.

            NAL Call Number:  QH301.N33

            Descriptors:  deoxyadenosines pharmacology, influenza A virus avian drug effects, Newcastle disease virus drug effects, RNA biosynthesis, virus replication drug effects, cell nucleolus metabolism, cell nucleus metabolism, cultured cells, chick embryo, depression, chemical, kinetics, tritium, uridine metabolism.

Makarova, K.S., Y.I. Wolf, E.P. Tereza, and V.A. Ratner (1998). Different patterns of molecular evolution of influenza A viruses in avian and human populations. Genetika 34(7): 890-896.  ISSN: 0016-6758.

            NAL Call Number:  QH431.A1G4

            Abstract:  Patterns of molecular evolution of the influenza virus proteins and genes are discussed. The subsets of all viral genes corresponding to statistically significant clusters on dendrogram were shown to fall into two distinct groups. The first group was characterized by the presence of an exact linear relationship between the year of the strain isolation and the evolutionary distance. The subsets of human influenza virus genes belong to this group. A method for eliminating the "frozen" strains from the subsets and for calculating the evolutionary rates without construction of phylogenetic trees has been elaborated. The substitution rates calculated according to this technique agreed with the data obtained previously. A linear relationship was not observed in the second group. This group was predominantly composed of avian influenza virus genes. The lack of linear correlation pointed to the cocirculation of a large amount of different influenza virus genomic segments in the avian population. An approach for an examination of the role of intragenic recombination in the development of the antigenic subtypes of hemagglutinin is suggested. Our results suggest that recombination did not play a considerable role in this process, and that all modern subtypes of this protein were probably formed before the introduction of the influenza viruses into the human population. These findings are consistent with the hypothesis that influenza viruses penetrated into human population from their pools in avian populations.

            Descriptors:  evolution and adaptation, genetics, influenza virus, human, avian.

Makarova, N.V., N.V. Kaverin, S. Krauss, D. Senne, and R.G. Webster (1999). Transmission of Eurasian avian H2 influenza virus to shorebirds in North America. Journal of General Virology 80(Pt. 12): 3167-71.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Influenza A virus of the H2 subtype caused a serious pandemic in 1957 and may cause similar outbreaks in the future. To assess the evolution and the antigenic relationships of avian influenza H2 viruses, we sequenced the haemagglutinin (HA) genes of H2 isolates from shorebirds, ducks and poultry in North America and derived a phylogenetic tree to establish their interrelationships. This analysis confirmed the divergence of H2 HA into two geographical lineages, American and Eurasian. One group of viruses isolated from shorebirds in North America had HA belonging to the Eurasian lineage, indicating an interregional transmission of the H2 gene. Characterization of HA with a monoclonal antibody panel revealed that the antigenicity of the Delaware strains differed from the other avian strains analysed. The data emphasizes the importance of avian influenza surveillance.

            Descriptors:  fowl plague transmission, fowl plague virology, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, Asia, birds virology, Europe, genes viral, hemagglutination inhibition tests, avian isolation and purification, North America, phylogeny, poultry virology.

Mandler, J., K. Muller, and C. Scholtissek (1991). Mutants and revertants of an avian influenza A virus with temperature-sensitive defects in the nucleoprotein and PB2. Virology 181(2): 512-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  ts19 is a temperature-sensitive (ts) mutant of the influenza A fowl plague virus with a defect in the nucleoprotein (NP). In ts19-infected chicken embryo cells all viral components are synthesized in normal yields at the nonpermissive temperature, but infectious virus is not formed. Under these conditions the migration of the NP and M of ts19 from the cell nucleus to the cytoplasm is affected. This ts defect is due to a single amino acid replacement (R162K) in a completely conserved region of the NP. Another mutant with a different defect in the NP is ts81. After infection with ts81 at 40 degrees no vRNA is being synthesized. By backcross of a revertant derived from ts81 many isolates with a ts defect in the PB2 protein were obtained. This ts defect seems to extragenically suppress the ts defect in the NP gene and to be dominant in a wild-type background.

            Descriptors:  genes viral, influenza A virus avian genetics, nucleoproteins genetics, suppression, genetic, viral core proteins genetics, amino acid sequence, chick embryo, crosses, genetic, avian growth and development, molecular sequence data, nucleoproteins chemistry, sensitivity and specificity, temperature, viral core proteins chemistry, virus replication genetics.

Mandler, J. and C. Scholtissek (1989). Localisation of the temperature-sensitive defect in the nucleoprotein of an influenza A/FPV/Rostock/34 virus. Virus Research 12(2): 113-21.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The nucleotide sequences of the nucleoprotein (NP) genes of fowl plague virus (FPV) and of a temperature-sensitive (ts) mutant (ts81) derived therefrom have been determined. The ts81-NP nucleotide sequence possesses a single nucleotide substitution in comparison to the wild type. This causes an amino acid exchange at position 332 of the NP. An alanine in the wild type-NP is substituted by a threonine in ts81-NP. This substitution leads to a significant difference in the secondary structure prediction. Although this mutation is located within the karyophilic region of the NP, the accumulation of the NP in ts81-infected cells is not significantly affected at 40 degrees C. Therefore, we assume that the cooperation with one of the polymerase proteins (P) is interfered with at 40 degrees C, leading to the loss of viral vRNA or replicative cRNA synthesis. The comparison of the FPV-NP nucleotide sequence to a previously published sequence of the same strain (Tomley and Roditi, 1984) highlights ten nucleotide differences, four of them leading to amino acid substitutions.

            Descriptors:  influenza A virus avian genetics, nucleoproteins genetics, viral core proteins, viral proteins genetics, amino acid sequence, base sequence, cell nucleus metabolism, DNA, viral genetics, avian metabolism, avian ultrastructure, molecular sequence data, mutation, nucleoproteins biosynthesis, RNA viral genetics, temperature, viral proteins biosynthesis.

Manvell, R.J., P.H. Jorgensen, O.L. Nielsen, and D.J. Alexander (1998). Experimental assessment of the pathogenicity of two avian influenza A H5 viruses in ostrich chicks (Struthio camelus) and chickens. Avian Pathology 27(4): 400-404.  ISSN: 0307-9457.

            NAL Call Number:  SF995.A1A9

            Abstract:  Virus excretion, immune response, and, for chickens, deaths were recorded in 3-week-old ostriches and chickens inoculated by either the intramuscular or intranasal route with one of two influenza A viruses of subtype H5. One of the viruses, A/turkey/England/50-92/91 (H5N1) (50/92), was highly pathogenic for chickens causing 5/5 deaths by each route of inoculation. The other virus, A/ostrich/Denmark-Q/72420/96 (H5N2) (72420/96), isolated from ostriches in quarantine in Denmark during 1996, was of low pathogenicity for chickens, causing no clinical signs by either route of inoculation. No significant clinical signs were seen in any of the ostriches infected with either of the viruses by either route of infection. Both viruses were recoverable from both species up to 12 days post-infection, and low serological responses were detected in surviving infected ostriches and chickens at 21 days after inoculation.

            Descriptors:  ostriches, chickens, chicks, avian influenza virus, susceptibility, experimental infections, pathogenicity, clinical aspects, antibody formation, mortality, application methods, intramuscular injection, virus shedding, intranasal administration.

Markushin, S., H. Ghiasi, N. Sokolov, A. Shilov, B. Sinitsin, D. Brown, A. Klimov, and D. Nayak (1988). Nucleotide sequence of RNA segment 7 and the predicted amino sequence of M1 and M2 proteins of FPV/Weybridge (H7N7) and WSN (H1N1) influenza viruses. Virus Research 10(2-3): 263-71.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Since the gene products (M1 and M2) of influenza virus RNA segment 7 have been implicated in host range restriction, sensitivity to the drug amantadine, virus yield in chicken embryos as well as in virus assembly and morphology, we have determined the nucleotide sequence of this RNA segment for an avian [A/FPV/Weybridge (H7N7)] and a human [A/WSN/33 (H1N1)] virus and compared it to that of the other influenza A virus strains. The results show that all ten strains of influenza A virus contain an identical number of nucleotides (1027 bases) in RNA segment 7 and an identical number of amino acids in M1 (252 aa) and M2 (97 aa) proteins. The observed amino acid changes are conservative in nature suggesting the requirement of a critical structure of both proteins in virus assembly. Furthermore, the presence of some consistent amino acid substitutions among different human and avian strains also supports the possible existence of host range and drug resistance determinants in M1 and M2 proteins.

            Descriptors:  influenza A virus avian genetics, human genetics, RNA viral genetics, viral matrix proteins genetics, amino acid sequence, base sequence, avian analysis, human analysis, molecular sequence data.

Markushin, S.G. and I.U.Z. Gendon (1981). Izuchenie reguliatsii virusspetsificheskikh polipeptidov ortomiksovirusov na modeli ts-mutanta virusa chumy, imeiushchego narushenie protsessa transkriptsii. [Study of regulation of orthomyxovirus virus-specific polypeptides using the ts-mutant of fowl plague virus having a transcription abnormality as a model]. Voprosy Virusologii (5): 604-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The synthesis of virus-specific polypeptides in cells infected with a ts-mutant of fowl plague virus with disturbed process of secondary transcription was studied. Synthesis of all virus-specific proteins was shown to occur under conditions providing for synthesis of polyA+ cRNA at the stage of primary transcription but with disturbance of the secondary transcription and blocking of polyA- cRNA and vRNA synthesis. No time regulation of virus-specific polypeptide synthesis was in effect.

            Descriptors:  influenza A virus avian metabolism, peptide synthesis, transcription, genetic, viral proteins biosynthesis, avian genetics, mutation.

Markushin, S.G. and Y.Z. Ghendon (1973). Genetic classification and biological properties of temperature-sensitive mutants of fowl plague virus. Acta Virologica 17(5): 369-76.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  influenza A virus avian classification, cultured cells, chick embryo, fluorouracil pharmacology, genetic complementation test, hydroxylamines pharmacology, avian pathogenicity, mutagens pharmacology, mutation drug effects, nitrites pharmacology, nitrosourea compounds pharmacology, plaque assay, recombination, genetic, temperature, virus replication drug effects.

Markushin, S.G. and Y.Z. Ghendon (1984). Studies of fowl plague virus temperature-sensitive mutants with defects in synthesis of virion RNA. Journal of General Virology 65(Pt. 3): 559-75.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Three different types of impairment in the synthesis of virion RNA (vRNA) were detected in three groups of temperature-sensitive (ts) mutants of fowl plague virus (FPV) having ts mutations in genes 1, 3 and 5 respectively. Normal synthesis of poly-(A+) cRNA, poly(A-) cRNA and vRNA was observed under non-permissive conditions early in infection in cells infected with the ts43 mutant having a ts mutation in gene 1 coding for the PB2 protein. However, 4 h after infection synthesis of vRNA ceased, synthesis of poly(A+) cRNA was reduced drastically, but the rate of poly(A-) cRNA synthesis was the same as that in cells infected with wild-type FPV. In cells infected with the ts 166 mutant having a ts mutation in gene 3, coding for the PA polypeptide, a drastic reduction was observed in poly(A+) cRNA synthesis under non-permissive conditions. Synthesis of poly(A-) cRNA was also reduced and synthesis of vRNA was not detected. The ts 60 mutant, having a ts mutation in gene 5 coding for the NP polypeptide, induced synthesis of all types of virus-specific RNA under non-permissive conditions, but the regulation of synthesis of vRNA and poly(A+) cRNA was affected, there being predominant syntheses of RNA segments 5 and 8 late in infection. In cells infected with mutants ts43 and ts 166 synthesis of virus-specific proteins was impaired, which reflected defects in the synthesis of virus-specific RNAs. The data obtained suggest that the PB2 protein may be contained in an enzyme complex responsible for synthesis of vRNA, that different enzyme complexes may be involved in the synthesis of poly(A-) cRNA and vRNA, and that the NP protein plays a significant role in the regulation of vRNA synthesis.

            Descriptors:  influenza A virus avian genetics, mutation, RNA viral biosynthesis, cycloheximide pharmacology, avian metabolism, peptide synthesis, recombination, genetic, ribonucleoproteins biosynthesis, temperature.

Markushin, S.G. and D.B. Ghenkina (1976). Principles of complementation interaction of ts mutants of orthomyxoviruses. Acta Virologica 20(6): 449-54.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The possibility of complementation between ts mutants of fowl plague virus (FPV) belonging to 5 different complementation groups was studied using various time intervals between inoculation of the cells with two complementation partners. The structural proteins of virions formed on complementation of individual ts mutants with wild virus were analysed by polyacrylamide gel electrophoresis after amino acid pulse label followed by pulse chase. The features of complementation interactions between the mutants are discussed.

            Descriptors:  influenza A virus avian growth and development, avian metabolism, mutation, genetic complementation test, peptide synthesis, temperature, viral proteins biosynthesis, virus replication.

Markushin, S.G., V.P. Ginzburg, A.M. Khaider, V.V. Iarosh, E.A. Ivas'ko, and A.I. Klimov (1992). Faktory, vyzyvaiushchie izmenenie antigennoi struktury gemaggliutinina viursa grippa. [Factors that cause a change in the antigenic structure of of the influenza virus hemagglutinin]. Voprosy Virusologii 37(4): 196-9.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Crossing of norakin-resistant mutant NR1 of A/Waybridge (H7N7) strain of fowl plague virus (FPV) with human influenza virus strains produced recombinants inheriting the hemagglutinin (HA) gene of the NR1 mutant and neuraminidase (NA) genes of human influenza virus strains. The R120 recombinant produced by crossing of NR1 with A/Taiwan/1/86 (H1N1) strain, unlike other recombinants and NR1 mutant, lost the capacity of reacting in H1 test with two monoclonal antibodies (MCA) to HA7: 71/4 and 46/6. The ts mutant A/FPV/Rostok which has ts-mutation in HA-gene also had changes in the antigenic specificity of HA. The RA and RB recombinants produced by crossing R120 with the A/Krasnodar/101/59 strain and inheriting HA-gene from R120 and NA-gene from A/Krasnodar/101/59 strain recovered the initial HA antigenic structure. No changes in the antigenic properties of HA were observed in the recombinants produced by crossing the original A/FPV/Waybridge strain with A/Taiwan/1/86 strain and inheriting HA-gene from the original A/FPV/Waybridge strain and NA-gene from A/Taiwan/1/86 strain. It is concluded that ts mutations in influenza virus HA-gene may be accompanied by changes in the antigenic specificity of this virus HA. The possibilities of manifestation of phenotypic suppression at the level of influenza virus virion membrane proteins and the causes of changes in the HA antigenic structure in this virus recombinants are discussed.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, human immunology, antiviral agents antagonists and inhibitors, chick embryo, crosses, genetic, drug resistance, microbial, epitopes genetics, epitopes immunology, genes viral immunology, hemagglutinins viral genetics, avian genetics, human genetics, mutation immunology, piperidines antagonists and inhibitors, recombination, genetic genetics, recombination, genetic immunology, temperature.

Markushin, S.G., V.A. Isachenko, E.V. Molibog, L.Y.A. Zakstelskaya, and Y.U.Z. Ghendon (1981). Gene homology and antigenic specificity of envelope proteins of avian influenza virus strains possessing haemagglutinin Havl.  Acta Virologica 25(2): 65-70.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Comparison of some avian influenza virus strains possessing haemagglutinin Havl revealed the greatest differences in strains A/FPV/Weybridge and A/FPV/Rostock/34. These strains differed in the degree of homology of eight genome fragments, electrophoretic mobility of the majority of proteins, size of plaques and rct42 marker and displayed significant differences in antigenic specificity of haemagglutinin. Strains A/FPV/Weybridge and A/FPV/Dobson proved to be more close in the degree of genome homology but differed in three genes, electrophoretic mobility of some proteins, size of plaques, rct42 marker and antigenic specificity of haemagglutinin. The data obtained indicate that avian influenza virus strains of the Havl subtype may differ from each other in the degree of gene homology and some other properties including antigenic specificity of haemagglutinin like influenza viruses with other haemagglutinin subtypes.

            Descriptors:  genes viral, hemagglutinins viral immunology, influenza A virus avian genetics, electrophoresis, polyacrylamide gel, epitopes, avian immunology, avian physiology, neuraminidase immunology, nucleic acid hybridization, plaque assay, temperature, viral envelope proteins, viral proteins immunology.

Marois, P., A. Boudreault, E. DiFranco, and V. Pavilanis (1971). Response of ferrets and monkeys to intranasal infection with human, equine and avian influenza viruses. Canadian Journal of Comparative Medicine Revue Canadienne De Medecine Comparee 35(1): 71-6.  ISSN: 0008-4050.

            NAL Call Number:  41.8 C162

            Descriptors:  Carnivora, influenza veterinary, monkey diseases microbiology, nose microbiology, orthomyxoviridae pathogenicity, respiratory tract infections microbiology, antigen antibody reactions, birds, cross reactions, haplorhini, hemagglutination inhibition tests, horses, immune sera, influenza immunology, orthomyxoviridae isolation and purification, respiratory tract infections immunology, turkeys, virus replication.

Massin, P., S. van der Werf, and N. Naffakh (2001). Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. Journal of Virology 75(11): 5398-404.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Human influenza A viruses replicate in the upper respiratory tract at a temperature of about 33 degrees C, whereas avian viruses replicate in the intestinal tract at a temperature close to 41 degrees C. In the present study, we analyzed the influence of low temperature (33 degrees C) on RNA replication of avian and human viruses in cultured cells. The kinetics of replication of the NP segment were similar at 33 and 37 degrees C for the human A/Puerto-Rico/8/34 and A/Sydney/5/97 viruses, whereas replication was delayed at 33 degrees C compared to 37 degrees C for the avian A/FPV/Rostock/34 and A/Mallard/NY/6750/78 viruses. Making use of a genetic system for the in vivo reconstitution of functional ribonucleoproteins, we observed that the polymerase complexes derived from avian viruses but not human viruses exhibited cold sensitivity in mammalian cells, which was determined mostly by residue 627 of PB2. Our results suggest that a reduced ability of the polymerase complex of avian viruses to ensure replication of the viral genome at 33 degrees C could contribute to their inability to grow efficiently in humans.

            Descriptors:  influenza A virus avian metabolism, human metabolism, RNA viral metabolism, viral proteins metabolism, cell line, mutation, viral genetics, temperature, time factors, transcription, genetic, viral proteins genetics, virus replication.

Masunaga, K., K. Mizumoto, H. Kato, A. Ishihama, and T. Toyoda (1999). Molecular mapping of influenza virus RNA polymerase by site-specific antibodies. Virology 256(1): 130-41.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  antibodies, viral, immunoglobulin G, influenza A virus avian enzymology, RNA replicase chemistry, base sequence, binding sites, antibody, chick embryo, enzyme linked immunosorbent assay, genome, viral, avian genetics, mutagenesis, site directed, oligodeoxyribonucleotides, RNA replicase metabolism, sequence deletion.

Matlin, K.S., H. Reggio, A. Helenius, and K. Simons (1981). Infectious entry pathway of influenza virus in a canine kidney cell line. Journal of Cell Biology 91(3, Pt. 1): 601-13.  ISSN: 0021-9525.

            NAL Call Number:  442.8 J828

            Abstract:  The entry of fowl plague virus, and avian influenza A virus, into Madin-Darby canine kidney (MDCK) cells was examined both biochemically and morphologically. At low multiplicity and 0 degrees C, viruses bound to the cell surface but were not internalized. Binding was not greatly dependent on the pH of the medium and reached an equilibrium level in 60-90 min. Over 90% of the bound viruses were removed by neuraminidase but not by proteases. When cells with prebound virus were warmed to 37 degrees C, part of the virus became resistant to removal b neuraminidase, with a half-time of 10-15 min. After a brief lag period, degraded viral material was released into the medium. The neuraminidase-resistant virus was capable of infecting the cells and probably did so by an intracellular route, since ammonium chloride, a lysosomotropic agent, blocked both the infection and the degradation of viral protein. When the entry process was observed by electron microscopy, viruses were seen bound primarily to microvilli on the cell surface at 0 degrees C and, after warming at 37 degrees C, were endocytosed in coated pits, coated vesicles, and large smooth-surfaced vacuoles. Viruses were also present in smooth-surfaced invaginations and small smooth-surfaced vesicles at both temperatures. At physiological pH, no fusion of the virus with the plasma membrane was observed. When prebound virus was incubated at a pH of 5.5 or below for 1 min at 37 degrees C, fusion was, however, detected by ferritin immunolabeling. t low multiplicity, 90% of the prebound virus became neuraminidase-resistant and was presumably fused after only 30 s at low pH. These experiments suggest that fowl plague virus enters MDCK cells by endocytosis in coated pits and coated vesicles and is transported to the lysosome where the low pH initiates a fusion reaction ultimately resulting in the transfer of the genome into the cytoplasm. The entry pathway of fowl plague virus thus resembles tht earlier described for Semliki Forest virus.

            Descriptors:  kidney microbiology, cell line, dogs, endocytosis, hydrogen-ion concentration, lysosomes microbiology, membrane fusion, microscopy, electron, temperature.

Matlin, K.S. and K. Simons (1983). Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation. Cell 34(1): 233-43.  ISSN: 0092-8674.

            NAL Call Number:  QH573.C42

            Abstract:  The transport kinetics of the influenza virus hemagglutinin from its site of synthesis to the apical plasma membrane of Madin-Darby canine kidney cells, a polarized epithelial cell line, were studied by a sensitive tryptic assay. Hemagglutinin acquired terminal sugars, as judged by sensitivity to endo-beta-N-acetylglucosaminidase H, 10-15 min after synthesis, and first appeared on the apical domain 15 min later. None of the pulse-labeled hemagglutinin accumulated on the basolateral domain. At 20 degrees C, terminal glycosylation continued, but no hemagglutinin was detected on the cell surface within 2 hr. If the incubation temperature was raised from 20 degrees C to 37 degrees C, hemagglutinin was quickly externalized, demonstrating that the inhibition at low temperature was reversible.

            Descriptors:  cell membrane metabolism, hemagglutinins viral, influenza A virus avian metabolism, oligosaccharides metabolism, viral proteins metabolism, biological transport, cell line, dogs, kinetics, temperature, viral envelope proteins.

Matrosovich, M., A. Tuzikov, N. Bovin, A. Gambaryan, A. Klimov, M.R. Castrucci, I. Donatelli, and Y. Kawaoka (2000). Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. Journal of Virology 74(18): 8502-12.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Interspecies transmission of influenza A viruses circulating in wild aquatic birds occasionally results in influenza outbreaks in mammals, including humans. To identify early changes in the receptor binding properties of the avian virus hemagglutinin (HA) after interspecies transmission and to determine the amino acid substitutions responsible for these alterations, we studied the HAs of the initial isolates from the human pandemics of 1957 (H2N2) and 1968 (H3N2), the European swine epizootic of 1979 (H1N1), and the seal epizootic of 1992 (H3N3), all of which were caused by the introduction of avian virus HAs into these species. The viruses were assayed for their ability to bind the synthetic sialylglycopolymers 3'SL-PAA and 6'SLN-PAA, which contained, respectively, 3'-sialyllactose (the receptor determinant preferentially recognized by avian influenza viruses) and 6'-sialyl(N-acetyllactosamine) (the receptor determinant for human viruses). Avian and seal viruses bound 6'SLN-PAA very weakly, whereas the earliest available human and swine epidemic viruses bound this polymer with a higher affinity. For the H2 and H3 strains, a single mutation, 226Q-->L, increased binding to 6'SLN-PAA, while among H1 swine viruses, the 190E-->D and 225G-->E mutations in the HA appeared important for the increased affinity of the viruses for 6'SLN-PAA. Amino acid substitutions at positions 190 and 225 with respect to the avian virus consensus sequence are also present in H1 human viruses, including those that circulated in 1918, suggesting that substitutions at these positions are important for the generation of H1 human pandemic strains. These results show that the receptor-binding specificity of the HA is altered early after the transmission of an avian virus to humans and pigs and, therefore, may be a prerequisite for the highly effective replication and spread which characterize epidemic strains.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian metabolism, receptors, virus metabolism,  amino acid sequence, amino acid substitution, disease outbreaks, ducks virology, hemagglutinin glycoproteins, influenza virus chemistry, avian isolation and purification, models, molecular, molecular sequence data, mutation, missense, phylogeny, protein binding, seals virology, sequence alignment, sialic acids metabolism, species specificity, swine virology.

Matrosovich, M., N. Zhou, Y. Kawaoka, and R. Webster (1999). The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties. Journal of Virology 73(2): 1146-55.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In 1997, 18 confirmed cases of human influenza arising from multiple independent transmissions of H5N1 viruses from infected chickens were reported from Hong Kong. To identify possible phenotypic changes in the hemagglutinin (HA) and neuraminidase (NA) of the H5 viruses during interspecies transfer, we compared the receptor-binding properties and NA activities of the human and chicken H5N1 isolates from Hong Kong and of H5N3 and H5N1 viruses from wild aquatic birds. All H5N1 viruses, including the human isolate bound to Sia2-3Gal-containing receptors but not to Sia2-6Gal-containing receptors. This finding formally demonstrates for the first time that receptor specificity of avian influenza viruses may not restrict initial avian-to-human transmission. The H5N1 chicken viruses differed from H5 viruses of wild aquatic birds by a 19-amino-acid deletion in the stalk of the NA and the presence of a carbohydrate at the globular head of the HA. We found that a deletion in the NA decreased its ability to release the virus from cells, whereas carbohydrate at the HA head decreased the affinity of the virus for cell receptors. Comparison of amino acid sequences from GenBank of the HAs and NAs from different avian species revealed that additional glycosylation of the HA and a shortened NA stalk are characteristic features of the H5 and H7 chicken viruses. This finding indicates that changes in both HA and NA may be required for the adaptation of influenza viruses from wild aquatic birds to domestic chickens and raises the possibility that chickens may be a possible intermediate host in zoonotic transmission.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian metabolism, human metabolism, alpha globulins metabolism, amino acid sequence, carbohydrates metabolism, chickens, fowl plague virology, Hong Kong, horseradish peroxidase metabolism, influenza veterinary, influenza virology, avian classification, avian isolation and purification, human classification, human isolation and purification, molecular sequence data, neuraminidase metabolism, ovomucin metabolism, phenotype, receptors, virus metabolism, sequence homology, amino acid.

Matrosovich, M.N., S. Krauss, and R.G. Webster ( 2001). H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity. Virology 281(2): 156-62.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, poultry virology, receptors, virus metabolism, amino acid substitution, Asia, binding sites, fowl plague transmission, fowl plague virology, hemagglutinin glycoproteins, influenza virus genetics, hemagglutinin glycoproteins, influenza virus metabolism, avian classification, avian genetics, human classification, human genetics, human metabolism, mutation, neuraminidase genetics, neuraminidase metabolism, phylogeny, viral envelope proteins genetics, viral envelope proteins metabolism.

Matrosovich, M.N., T.Y. Matrosovich, T. Gray, N.A. Roberts, and H.D. Klenk (2004). Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proceedings of the National Academy of Sciences of the United States of America 101(13): 4620-4.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  The recent human infections caused by H5N1, H9N2, and H7N7 avian influenza viruses highlighted the continuous threat of new pathogenic influenza viruses emerging from a natural reservoir in birds. It is generally believed that replication of avian influenza viruses in humans is restricted by a poor fit of these viruses to cellular receptors and extracellular inhibitors in the human respiratory tract. However, detailed mechanisms of this restriction remain obscure. Here, using cultures of differentiated human airway epithelial cells, we demonstrated that influenza viruses enter the airway epithelium through specific target cells and that there were striking differences in this respect between human and avian viruses. During the course of a single-cycle infection, human viruses preferentially infected nonciliated cells, whereas avian viruses as well as the egg-adapted human virus variant with an avian virus-like receptor specificity mainly infected ciliated cells. This pattern correlated with the predominant localization of receptors for human viruses (2-6-linked sialic acids) on nonciliated cells and of receptors for avian viruses (2-3-linked sialic acids) on ciliated cells. These findings suggest that although avian influenza viruses can infect human airway epithelium, their replication may be limited by a nonoptimal cellular tropism. Our data throw light on the mechanisms of generation of pandemic viruses from their avian progenitors and open avenues for cell level-oriented studies on the replication and pathogenicity of influenza virus in humans.

            Descriptors:  influenza A virus, avian pathogenicity, human pathogenicity, respiratory mucosa microbiology, bronchi, cell line, dogs, avian isolation and purification, avian physiology, human isolation and purification, human physiology, kidney, lectins, microscopy, confocal, nasal mucosa microbiology, sialic acids analysis, trachea.

Matrosovich, M.N., T.Y. Matrosovich, T. Gray, N.A. Roberts, and H.D. Klenk (2004). Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. Journal of Virology 78(22): 12665-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza virus neuraminidase (NA) plays an essential role in release and spread of progeny virions, following the intracellular viral replication cycle. To test whether NA could also facilitate virus entry into cell, we infected cultures of human airway epithelium with human and avian influenza viruses in the presence of the NA inhibitor oseltamivir carboxylate. Twenty- to 500-fold less cells became infected in drug-treated versus nontreated cultures (P < 0.0001) 7 h after virus application, indicating that the drug suppressed the initiation of infection. These data demonstrate that viral NA plays a role early in infection, and they provide further rationale for the prophylactic use of NA inhibitors.

            Descriptors:  bronchi virology, nasal mucosa virology, neuraminidase physiology, orthomyxoviridae physiology, trachea virology, acetamides pharmacology, orthomyxoviridae enzymology.

Matsuda, K., C.H. Park, Y. Sunden, T. Kimura, K. Ochiai, H. Kida, and T. Umemura (2004). The vagus nerve is one route of transneural invasion for intranasally inoculated influenza A virus in mice. Veterinary Pathology 41(2): 101-7.  ISSN: 0300-9858.

            NAL Call Number:  41.8 P27

            Abstract:  Intranasally inoculated neurotropic influenza viruses in mice infect not only the respiratory tract but also the central nervous system (CNS), mainly the brain stem. Previous studies suggested that the route of invasion of virus into the CNS was via the peripheral nervous system, especially the vagus nerve. To evaluate the transvagal transmission of the virus, we intranasally inoculated unilaterally vagectomized mice with a virulent influenza virus (strain 24a5b) and examined the distribution of the viral protein and genome by immunohistochemistry and in situ hybridization over time. An asymmetric distribution of viral antigens was observed between vagal (nodose) ganglia: viral antigen was detected in the vagal ganglion of the vagectomized side 2 days later than in the vagal ganglion of the intact side. The virus was apparently transported from the respiratory mucosa to the CNS directly and decussately via the vagus nerve and centrifugally to the vagal ganglion of the vagectomized side. The results of this study, thus, demonstrate that neurotropic influenza virus travels to the CNS mainly via the vagus nerve.

            Descriptors:  brain stem virology, influenza A virus, avian, orthomyxoviridae infections virology, vagus nerve virology, immunohistochemistry, in situ hybridization, lung virology, mice, nodose ganglion virology, respiratory mucosa virology.

Matsuura, Y., R. Yanagawa, and H. Noda (1979). Experimental infection of mink with influenza A viruses. Brief report. Archives of Virology 62(1): 71-6.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Mink were found to be susceptible to the intranasal inoculation of human, swine, equine and avian influenza A viruses. The viruses were recovered until the 7th post inoculation (p.i.) day from the respiratory tract. The inoculated mink showed antibody response against these viruses. Contact infection in mink with A/Kumamoto/22/77 (H3N2) was possible.

            Descriptors:  influenza A virus pathogenicity, orthomyxoviridae infections microbiology, antibodies, viral biosynthesis, disease models, animal, hemagglutination inhibition tests, influenza A virus immunology, influenza A virus isolation and purification, orthomyxoviridae infections immunology, orthomyxoviridae infections transmission, respiratory system microbiology.

McCahon, D. and G.C. Schild (1971). An investigation of some factors affecting cross-reactivation between influenza A viruses. Journal of General Virology 12(3): 207-19.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  genetics, microbial, influenza A virus avian pathogenicity, orthomyxoviridae pathogenicity, recombination, genetic, antigens, viral analysis, azirines pharmacology, chick embryo, fetal membranes, fibroblasts, heat, hemagglutination inhibition tests, hemagglutinins viral analysis, horses, immune sera, avian drug effects, avian immunology, avian radiation effects, neuraminidase analysis, orthomyxoviridae immunology, orthomyxoviridae radiation effects, quinones pharmacology, rabbits, radiation effects, tissue culture, ultraviolet rays, virus cultivation.

McCauley, J.W., B.W. Mahy, and S.C. Inglis (1982). Nucleotide sequence of fowl plague virus RNA segment 7. Journal of General Virology 58(Pt. 1): 211-5.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Nucleotide sequence analysis of a recombinant DNA clone of RNA segment 7 from FPV/Rostock/34 has shown it to be highly conserved in comparison with RNA segment 7 from two human strains (Allen et al., 1980; Winter & Fields, 1980; Lamb & Lai, 1981). FPV RNA segment 7 contains the coding capacity for two polypeptide chains. The sequence homology between RNA segment 7 of avian and human viruses was greater than 90%, and most of the changes did not result in amino acid substitutions.

            Descriptors:  influenza A virus avian genetics, RNA viral analysis, base sequence, cloning, molecular,  DNA restriction enzymes, DNA, recombinant analysis, Escherichia coli genetics, plasmids.

McCauley, J.W. and C.R. Penn (1990). The critical cut-off temperature of avian influenza viruses. Virus Research 17(3): 191-8.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  We have measured the pathogenicity for 6-week-old chicks of infection by H7 avian influenza viruses. One virus, strain S3 from A/FPV/Rostock/34(H7N1) showed a temperature sensitive phenotype at 41.5 degrees C and reduced pathogenicity. By analysis of reassortants made between virus S3 and A/FPV/Dobson/27(H7N7), a fully pathogenic virus, two conclusions arise. (1) The critical cut-off temperature for avian influenza virus in 6-week-old chicks is 41.5 degrees. (2) RNA segment 1 of virus S3 is responsible for the lack of pathogenicity in reassortant viruses. Nucleotide sequencing of RNA segment 1 from S3 and its parent, A/FPV/Rostock/34 has revealed a single mutation at nucleotide 1561. This results in a substitution of isoleucine for leucine at amino acid position 512 in the cap-binding protein, PB2.

            Descriptors:  carrier proteins genetics, fowl plague microbiology, influenza A virus avian pathogenicity, RNA caps metabolism, amino acid sequence, base sequence, carrier proteins metabolism, chickens, avian genetics, avian growth and development, molecular sequence data, mutation, phenotype, plaque assay, RNA cap binding proteins, RNA viral genetics,  temperature.

McDowell, W., A. Tlusty, R. Rott, J.N. BeMiller, J.A. Bohn, R.W. Meyers, and R.T. Schwarz (1988). Inhibition of glycoprotein oligosaccharide processing in vitro and in influenza-virus-infected cells by alpha-D-mannopyranosylmethyl-p-nitrophenyltriazene. Biochemical Journal 255(3): 991-8.  ISSN: 0264-6021.

            NAL Call Number:  QP501,B64

            Abstract:  The effects of alpha-D-mannopyranosylmethyl-p-nitrophenyltriazene (MMNT) on mannosidases involved in asparagine-linked oligosaccharide processing were investigated. MMNT was found to inhibit the activity of rat liver Golgi alpha-mannosidase I in a concentration-dependent manner (50% inhibition with 0.18 mM-MMNT), whereas rat liver endoplasmic-reticulum alpha-mannosidase appeared to be resistant (less than 5% inhibition at 1 mM-MMNT). Jack-bean alpha-mannosidase was also sensitive to inhibition by MMNT (50% inhibition with 0.32 mM-MMNT). Treatment of influenza-virus-infected chick-embryo cells with 1 mM-MMNT led to a decrease in the formation of complex-type asparagine-linked oligosaccharides and an accumulation of high-mannose-type oligosaccharides with the composition Man8(GlcNAc)2 and Man7(GlcNAc)2 on the viral glycoproteins. The biological activities of influenza-virus haemagglutinin and neuraminidase synthesized in the presence of 1 mM-MMNT remained unchanged, but the virus was less infectious than the control.

            Descriptors:  glycoproteins metabolism, mannosidases antagonists and inhibitors, oligosaccharides metabolism, triazenes pharmacology, chick embryo, endoplasmic reticulum drug effects, endoplasmic reticulum metabolism, fabaceae drug effects, fabaceae enzymology, Golgi apparatus drug effects, Golgi apparatus enzymology, influenza A virus avian physiology, liver drug effects, liver enzymology, mannans metabolism, plants, medicinal, rats, alpha mannosidase.

McGeoch, D., P. Fellner, and C. Newton (1976). Influenza virus genome consists of eight distinct RNA species. Proceedings of the National Academy of Sciences of the United States of America 73(9): 3045-9.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  The genomic RNA of the avian influenza A virus, fowl plague, was fractionated into eight species by electrophoresis in polyacrylamide-agarose gels containing 6 M urea. The separated 32P-labeled RNA species were characterized by digestion with RNase T1 and fractionation of the resulting oligonucleotides by two-dimensional gel electrophoresis; this demonstrated that each species has a distinct nucleotide sequence. A tentative correlation of each genome RNA species with the virus protein that it encodes was made.

            Descriptors:  influenza A virus avian analysis, RNA viral analysis, base sequence, genes, structural, molecular weight, oligoribonucleotides analysis, viral isolation and purification, viral proteins biosynthesis.

McKimm Breschkin, J.L.,  A. Sahasrabudhe, T.J. Blick, M. McDonald, P.M. Colman, G.J. Hart, R.C. Bethell, and J.N. Varghese (1998). Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors. Journal of Virology 72(3):  2456-62.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The influenza virus neuraminidase (NA)-specific inhibitor zanamivir (4-guanidino-Neu5Ac2en) is effective in humans when administered topically within the respiratory tract. The search for compounds with altered pharmacological properties has led to the identification of a novel series of influenza virus NA inhibitors in which the triol group of zanamivir has been replaced by a hydrophobic group linked by a carboxamide at the 6 position (6-carboxamide). NWS/G70C variants generated in vitro, with decreased sensitivity to 6-carboxamide, contained hemagglutinin (HA) and/or NA mutations. HA mutants bound with a decreased efficiency to the cellular receptor and were cross-resistant to all the NA inhibitors tested. The NA mutation, an Arg-to-Lys mutation, was in a previously conserved site, Arg292, which forms part of a triarginyl cluster in the catalytic site. In enzyme assays, the NA was equally resistant to zanamivir and 4-amino-Neu5Ac2en but showed greater resistance to 6-carboxamide and was most resistant to a new carbocyclic NA inhibitor, GS4071, which also has a hydrophobic side chain at the 6 position. Consistent with enzyme assays, the lowest resistance in cell culture was seen to zanamivir, more resistance was seen to 6-carboxamide, and the greatest resistance was seen to GS4071. Substrate binding and enzyme activity were also decreased in the mutant, and consequently, virus replication in both plaque assays and liquid culture was compromised. Altered binding of the hydrophobic side chain at the 6 position or the triol group could account for the decreased binding of both the NA inhibitors and substrate.

            Descriptors:  conserved sequence, enzyme inhibitors pharmacology, influenza A virus human enzymology, mutation, N-acetylneuraminic acid analogs and derivatives, neuraminidase antagonists and inhibitors, neuraminidase genetics,  acetamides chemistry, acetamides pharmacology, adsorption, binding sites, birds, cell line, dogs, drug resistance, microbial, enzyme inhibitors chemistry, heating, hemagglutinin glycoproteins, influenza virus genetics, avian enzymology, human growth and development, human metabolism, kinetics, molecular structure, N-acetylneuraminic acid chemistry, N-acetylneuraminic acid pharmacology, phenotype, plaque assay, sialic acids chemistry, sialic acids pharmacology, substrate specificity, virus replication.

Medvedeva, T.E., K.V. Lisovskaya, F.I. Polezhaev, L.M. Garmashova, G.I. Alexandrova, and Y.Z. Ghendon (1984). Location of ts defects in the genome of cold-adapted recombinant influenza A virus vaccine strains. Acta Virologica 28(3): 204-11.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The ts phenotype and location of ts mutations were studied in the genome of parent viruses and those obtained by recombination of cold-adapted strains A/Leningrad/134/17/57 or A/Leningrad/134/47/57 with epidemic H1N1 and H3N2 influenza A virus strains. The epidemic H1N1 and H3N2 strains under study possessed a ts phenotype and contained ts mutations in one or two genes. The ts phenotype was lost following three clonings at 40 degrees C, suggesting that influenza virus strains isolated from humans may be heterogeneous and contain virions either carrying or not carrying the ts mutations in their genomes. Two cold-adapted strains possessing a distinct ts phenotype contained ts mutations in three (A/Leningrad/134/17/57 virus after 17 passages at 25 degrees C) or in five (A/Leningrad/134/47/57 variant after 30 additional passages at 25 degrees C) genes coding for non-glycosylated proteins. When compared with cold-adapted donor strains, the recombinants had either the same set or additional ts mutations. However, no ts mutation was detected in a gene which had been inherited from the donor strain. It is suggested that, in addition to the analysis of the genome composition, in cold-adapted recombinant influenza virus strains recommended as vaccine candidates it is necessary to control the number of genes containing ts mutations.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, mutation, vaccines, attenuated, acclimatization, adult, child, cold, avian immunology, avian pathogenicity, human immunology, human pathogenicity, phenotype, recombination, genetic, variation genetics, virulence.

Meijer, A., J.A. van der Goot, G. Koch, M. van Boven, and T.G. Kimman (2004). Oseltamivir reduces transmission, morbidity, and mortality of highly pathogenic avian influenza in chickens. International Congress Series 1263: 495-498.

            Abstract:  The effect of the neuraminidase inhibitors zanamivir and oseltamivir on the transmission of highly pathogenic avian influenza (HPAI) in chickens was studied. Per group, five chickens inoculated with HPAI A/Chicken/Pennsylvania/1370/83 H5N2 virus were placed 1 day post-inoculation (p.i.) in one cage with five contact chickens. Inoculated and contact chickens were treated twice daily from 1 day before inoculation up to day 7 p.i. All untreated inoculated and contact chickens became infected and four inoculated and two contact chickens died. Similarly, all of the zanamivir-treated inoculated and contact chickens became infected and all inoculated and four contact chickens died. Obviously, locally active zanamivir has no effect. In contrast, although oseltamivir could not prevent tracheal infection of the inoculated chickens, none had an infected cloaca and only one died. More important, only after stopping treatment three contact chickens became positive, suggesting limited transmission within or after the treatment period. In conclusion, treatment with systemically active oseltamivir limits to a large extent a severe outcome and chicken-to-chicken transmission of HPAI virus.

            Descriptors:  highly pathogenic avian influenza virus, chicken, transmission, antiviral treatment, antiviral prophylaxis, neuraminidase inhibitors, zanamivir, oseltamivir.

Melnikov, S.Y.A., A.V. Mikheeva, and Y.Z. Ghendon (1982). Studies on polysomes synthesizing influenza virus haemagglutinin. Archives of Virology 74(4): 299-310.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A fraction of polysomes synthesizing fowl plague virus (FPV) haemagglutinin (HA) was isolated from an infected chick embryo fibroblast (CEF) culture using a double immunoprecipitation assay. In an immunoprecipitate of HA-synthesizing polysomes (HA precipitate) the content of the HA polypeptide was increased with respect to the M1 + NS1 polypeptides as compared to a preparation of unprecipitated polysomes. In the HA precipitate, besides mRNA coding for HA synthesis, we have detected mRNAs corresponding to genes 1, 2 and 3 coding for high molecular weight P proteins. Studies of a cytoplasmic extract (CE) from FPV-infected CEF cultures in a sucrose density gradient revealed a fraction of polysomes with a sedimentation value of about 500S; the composition of virus-specific polypeptides and mRNA of the fraction was similar to that of the HA precipitate. It is thought that P proteins are synthesized on membrane-bound polysomes located closely to HA-synthesizing polysomes.

            Descriptors:  hemagglutinins isolation and purification,  influenza A virus avian metabolism, polyribosomes metabolism, viral proteins biosynthesis, cultured cells, chick embryo, fowl plague immunology, fowl plague metabolism, avian immunology, RNA, messenger metabolism.

Melnikov, S.Y.A., A.V. Mikheeva, I.A. Leneva, and Y.Z. Ghendon (1985). Interaction of M protein and RNP of fowl plague virus in vitro. Virus Research 3(4): 353-65.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The ability of the fowl plague virus (FPV) M protein to form a complex with FPV RNP and to inhibit the RNP transcriptase activity in vitro depended on NaCl concentration and did not depend on the concentration of nonionic detergents. The results obtained indicate that the M protein-RNP links formed were of an electrostatic rather than a hydrophobic nature. As demonstrated using individual RNP components, vRNA and RNA-free protein structures, M protein formed complexes only with vRNA, and the complex formation was salt-dependent. Analysis of products formed in the in vitro system containing RNP of FPV in the presence of the M protein showed impairment in the transcription of all RNA segments. The degree of inhibition correlated with the size of a segment, transcription of high molecular weight RNA segments being inhibited significantly more than that of low molecular weight RNA segments.

            Descriptors:  influenza A virus avian metabolism, ribonucleoproteins metabolism, viral proteins metabolism, cultured cells, chick embryo, avian genetics, RNA replicase metabolism, RNA viral isolation and purification, ribonucleoproteins isolation and purification, transcription, genetic, viral matrix proteins, viral proteins isolation and purification.

Meloni, G.A., L. Conventi, F. Busolo, and G. Bertolini (1980). Effect of Mycoplasma contamination on replication of some DNA and RNA viruses in cultured cells. Microbiologica  3(4): 461-469.  ISSN: 0391-5352.

            NAL Call Number:  QR1.M57

            Descriptors:  Mycoplasma, contamination, viruses, DNA, RNA, arginine, cell culture.

Men'shikh, L.K., I.A. Rudneva, G.V. Kornilaeva, M.I. Sokolov, and V.M. Zhdanov (1975). Infektsionnost' RNK virusa istinnoi chumy ptits v protsesse infektsii [Infectivity of fowl  plague virus RNA in the process of infection]. Voprosy Virusologii (6): 722-5.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The conditions for isolation and detection of the infectious properties of nucleic acid preparations extracted from cells infected with fowl plague virus were studied. It is suggested that double-stranded virus-specific RNAs possess the infectious properties.

            Descriptors:  influenza A virus avian growth and development, RNA, viral, virus replication, cultured cells.

Meulemans, G., M.C. Carlier, M. Gonze, and P. Petit (1987). Comparison of hemagglutination-inhibition, agar gel precipitin, and enzyme-linked immunosorbent assay for measuring antibodies against influenza viruses in chickens. Avian Diseases 31(3): 560-3.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Individual variations in serological response to avian influenza virus infection were demonstrated after experimental infection of specific-pathogen-free chickens with H6N2 influenza virus. Homologous antibodies were detected from the 6th to the 157th day after infection using hemagglutination-inhibition or enzyme-linked immunosorbent assay and from the 11th to the 157th day by agar gel precipitation test.

            Descriptors:  antibodies, viral analysis, chickens immunology, fowl plague immunology, influenza A virus avian immunology, chick embryo, enzyme linked immunosorbent assay, hemagglutination inhibition tests veterinary, precipitin tests veterinary, specific pathogen free organisms.

Mikheeva, A. and Y.Z. Ghendon (1982). Intrinsic interference between influenza A and B viruses. Archives of Virology 73(3-4): 287-94.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Reproduction and synthesis of virus-specific macromolecules were studied in chick embryo fibroblast cultures co-infected with influenza viruses type A (FPV) and B (B/Japan/73). When a multiplicity of infection (MOI) of B/Japan/73 virus (10 EID50/cell and higher) was equal to, or exceeded that of FPV, formation of infectious FPV virions in coinfected cells was suppressed significantly. At equal MOI of FPV and B/Japan/73 synthesis of all proteins of one partner and some proteins of the other was observed. However, when a MOI of one virus was 10 times higher than that of the other, proteins of the virus used at a higher MOI were formed. Studies of the synthesis of virus-specific cRNAs formed in the presence of cycloheximide have shown that at equal MOI. cRNAs were detected that corresponded only to one of the partners involved in the reproduction. The data obtained suggest that intrinsic interference between A and B viruses occurs at a stage of primary transcription.

            Descriptors:  influenza A virus avian physiology, orthomyxoviridae physiology, viral interference, cultured cells, chick embryo, cycloheximide pharmacology, RNA viral biosynthesis, transcription, genetic, viral proteins biosynthesis.

Mikheeva, A.V., A.Y.A. Melnikov, and E. Anisimova (1989). Action of rimantadine on the structure of influenza A virus haemagglutinin. Acta Virologica 33(2): 131-6.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Rimantadine prevents the conformational changes of influenza virus haemagglutinin (HA) caused by acid pH and the acquisition of sensitivity to trypsin, protects the haemolytic activity from inactivation and prevents the morphological changes of HA spikes on the virus surface.

            Descriptors:  adamantane analogs and derivatives, hemagglutinins viral analysis, influenza A virus avian drug effects, membrane fusion drug effects, rimantadine pharmacology, chick embryo, hemagglutinin glycoproteins, influenza virus, hydrogen-ion concentration, avian immunology, avian physiology, protein conformation drug effects, trypsin, virion drug effects, virion ultrastructure.

Miller Podraza, H., L. Johansson, P. Johansson, T. Larsson, M. Matrosovich, and K.A. Karlsson (2000). A strain of human influenza A virus binds to extended but not short gangliosides as assayed by thin-layer chromatography overlay. Glycobiology 10(10): 975-82.  ISSN: 0959-6658.

            NAL Call Number:  QP552.G59G593

            Abstract:  A human strain of influenza virus (A, H1N1) was shown to bind in an unexpected way to leukocyte and other gangliosides when compared with avian virus (A, H4N6) as assayed on TLC plates. The human strain bound only to species with about 10 or more sugars, while the avian strain bound to a wide range of gangliosides including the 5-sugar gangliosides. By use of specific lectins, antibodies, and FAB and MALDI-TOF mass spectrometry an attempt was done to preliminary identify the sequences of leukocyte gangliosides recognized by the human strain. The virus binding pattern did not follow binding by VIM-2 monoclonal antibody and was not identical with binding by anti-sialyl Lewis x antibody. There was no binding by the virus of linear NeuAcalpha3- or NeuAcalpha6-containing gangliosides with up to seven monosaccharides per mol of ceramide. Active species were minor NeuAcalpha6-containing molecules with probably repeated HexHexNAc units and fucose branches. This investigation demonstrates marked distinctions in the recognition of gangliosides between avian and human influenza viruses. Our data emphasize the importance of structural factors associated with more distant parts of the binding epitope and the complexity of carbohydrate recognition by human influenza viruses.

            Descriptors:  gangliosides metabolism, influenza A virus human metabolism, carbohydrate sequence, chromatography, thin layer methods, avian metabolism, leukocytes chemistry, molecular sequence data, species specificity, spectrometry, mass, fast atom bombardment, spectrometry, mass, matrix assisted laser desorption ionization.

Miller Podraza, H., T. Larsson, J. Nilsson, S. Teneberg, M. Matrosovich, and L. Johansson (1998). Epitope dissection of receptor-active gangliosides with affinity for Helicobacter pylori and influenza virus. Acta Biochimica Polonica 45(2): 439-49.  ISSN: 0001-527X.

            NAL Call Number:  385 AC85

            Abstract:  Receptor-active gangliosides with affinity for Helicobacter pylori and influenza virus were chemically modified and analyzed by negative ion fast atom bombardment mass spectrometry (FAB MS) or electron ionization mass spectrometry (EI MS) after permethylation. Derivatizations included mild periodate oxidation of the sialic acid glycerol tail or conversion of the carboxyl group to primary alcohol or amides. The modified gangliosides were then tested for binding affinity using thin-layer plates overlaid with labeled microbes or microbe-derived proteins. Mild periodate oxidation, which shortens sialic acid tail without destruction of sugar cores, abolished or drastically reduced binding of H. pylori and avian influenza virus to sialyl-3-paragloboside (S-3-PG). The same effect was observed in the case of binding of the human influenza virus to receptor-active gangliosides of human leukocytes. Conversion of S-3-PG or leukocyte gangliosides to primary alcohols or amides also abolished the binding. However, mild periodate oxidation had no effect on binding of NAP (neutrophil-activating protein of H. pylori) to the active ganglioside.

            Descriptors:  gangliosides metabolism, Helicobacter pylori metabolism, orthomyxoviridae metabolism, binding sites, gangliosides chemistry, methylation, receptors, cell surface chemistry, receptors, cell surface metabolism, spectrum analysis.

Minor, P.D. and N.J. Dimmock (1979). The coupling of transcription from influenza virions to translation in vitro. Archives of Virology 59(3): 201-12.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The optimum conditions for the coupling of fowl plague virus (FPV) transcription to an in vitro reticulocyte translation system have been established and shown to be close to those required for maximum RNA synthesis by purified FPV virions. Products have been characterized by the peptides they yield on limited proteolysis in SDS and it has been shown that virus nucleoprotein (NP) and matrix (M) protein are made. The smallest virus coded polypeptide, the non-structural protein (NS), is made in only small amounts in the coupled system although it is a major virus coded product of infected cells early in infection.

            Descriptors:  influenza A virus avian metabolism, RNA viral biosynthesis, viral proteins biosynthesis, cell free system, fluorometry, avian genetics, peptide synthesis, rabbits, reticulocytes metabolism, transcription, genetic, translation, genetic.

Minor, P.D. and N.J. Dimmock (1975). Inhibition of synthesis of influenza virus proteins: evidence of two host-cell-dependent events during multiplication. Virology 67(1): 114-23.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, viral proteins biosynthesis, virus replication, amanitins pharmacology, camptothecin pharmacology, cell line, cell nucleus metabolism, dactinomycin pharmacology, hemagglutinins viral analysis, avian growth and development, avian immunology, neuraminidase biosynthesis, RNA viral biosynthesis.

Minor, P.D. and N.J. Dimmock (1976). The multiplication of influenza virus in enucleated BHK cells fused with chicken erythrocytes. Virology 69(1): 336-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cell nucleus metabolism, influenza A virus avian growth and development, virus replication, antigens, viral analysis, cell fractionation, cell fusion, cycloheximide pharmacology, dactinomycin pharmacology, hemagglutinins viral, hybrid cells, neuraminidase biosynthesis, neuraminidase immunology, ribonucleoproteins biosynthesis, ribonucleoproteins immunology, viral proteins biosynthesis, viral proteins immunology.

Minor, P.D. and N.J. Dimmock (1977). Selective inhibition of influenza virus protein synthesis by inhibitors of DNA function. Virology 78(2): 393-406.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian drug effects, viral proteins biosynthesis, 4 nitroquinoline 1 oxide pharmacology, camptothecin pharmacology, cell line, dactinomycin pharmacology, daunorubicin pharmacology, echinomycin pharmacology, ethidium pharmacology, hemagglutinins viral, avian growth and development, avian metabolism, neuraminidase biosynthesis, Newcastle disease virus drug effects, Newcastle disease virus growth and development, Newcastle disease virus metabolism, nogalamycin pharmacology, plicamycin pharmacology, proflavine pharmacology, virus replication drug effects.

Mitchell, B.W. and M. Brugh (1982). Comparison of electrocardiograms of chickens infected with viscerotropic velogenic Newcastle disease virus and virulent avian influenza virus. American Journal of Veterinary Research 43(12): 2274-8.  ISSN: 0002-9645.

            NAL Call Number:  41.8 Am3A

            Abstract:  Electrocardiograms of chickens infected with viscerotropic velogenic Newcastle disease virus (NDV) or virulent avian influenza virus (AIV) were characterized and compared. The ECG were monitored by radiotelemetry and were recorded twice daily before virus infection and during the course of the infection. Thirteen lead II intervals, segments, and amplitudes were measured and analyzed. The ECG of NDV-infected chickens were characterized by lengthened (P less than or equal to 0.05) ST segments and increased (P less than or equal to 0.05) P amplitudes. The ECG of AIV-infected chickens were characterized by lengthened (P less than or equal to 0.05) RS intervals, ST segments, TP intervals, and PR segments and by increased (P less than or equal to 0.05) P amplitudes. The TP intervals and PR segments of ECG of AIV-infected chickens were significantly (P less than or equal to 0.05) longer than those of NDV-infected chickens. The pronounced conduction delays indicated in the ECG of AIV-infected chickens may have diagnostic importance.

            Descriptors:  chickens, fowl plague physiopathology, heart physiopathology, Newcastle disease physiopathology, electrocardiography veterinary, influenza A virus avian pathogenicity, Newcastle disease virus pathogenicity, specific pathogen free organisms, virulence.

Mitchell, B.W. and M.L. Perdue (1991). Automated monitoring system for determining embryo movement and death times following virus infection. Avian Diseases 35(4): 840-6.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Design and performance information is presented on an automated embryo-monitoring system for intact eggs. The computer-based system has been used successfully for several months to characterize viral pathogenicity in embryonated eggs. Features include electronic sensing of embryo movement, automatic quantification of the amount of movement, and automatic recording of the results on electronic media. The system does not require that eggs be removed from the incubator or that the incubator be opened during the course of an experiment, as is necessary with the manual candling technique. It has greatly improved discrimination of viral pathogenicity effects in fertile eggs because of its sensitivity and reduced intervals between observations. One important potential application involves using the system to measure the effects on virulence of mixing closely related variants of the same strain of virus that differ in pathogenicity, which is the biological scenario most likely approximating a natural disease outbreak.

            Descriptors:  chick embryo microbiology, influenza A virus avian pathogenicity, microcomputers, chick embryo physiology, lethal dose 50, movement, software.

Molibog, E.V., I. Konstantinov Zibelist, G. Starke, and L.I.A. Zakstel'skaia (1979). Shtammovaia spetsifichnost' antineiraminidaznykh antitel serotipa N2 shtammov virusa grippa u perebolevshikh. [Strain specificity of the antineuraminidase antibodies of influenza virus serotype N2 strains in convalescents]. Voprosy Virusologii (6): 631-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Antineuraminidase antibody was determined in the subjects who had suffered influenza during the epidemics of 1970-1975 in the GDR. As early as 1970 the highest titers of antibody (greater than or equal to 1:60) were found not only to the prototype A/Hong Kong/1/68 strain but also to its subsequent drift variants A/England/42/72, A/Port Chalmers/1/73. Some subjects had antineuraminidase antibody to avian influenza virus.

            Descriptors:  antibodies, viral analysis, influenza immunology, influenza A virus human immunology, neuraminidase immunology, adult, child, child, preschool, convalescence, disease outbreaks epidemiology, Germany, East, influenza epidemiology, human enzymology, neuraminidase antagonists and inhibitors.

Molibog, E.V., T.V. Pysina, and A.S. Gorbunova ( 1968). Sootnoshenie mezhdu eliuikuiushchei i neiraminidaznoi aktivost'iu virusov gruppa tipa A cheloveka, mlekopitaiushchikh i ptits. [Relationship between eluting and neuraminidase activity of human, mammalian and avian influenza type A viruses]. Voprosy Virusologii 13(5):  623-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  neuraminidase analysis, orthomyxoviridae enzymology, orthomyxoviridae physiology.

Molotkovskii, I.u.G., E.M. Manevich, V.I. Shvets, M.M. Smirnova, and V.N. Krylova (1983).  Issledovanie stroeniia membran remantadinchuvstvitel'nogo i remantadinustoichivogo virusa grippa s pomoshch'iu fliuorestsentnykh fosfolipidnykh zondov. [Membrane structure of remantadine-sensitive and remantadine-resistant influenza virus studied with fluorescent phospholipid probes]. Voprosy Virusologii (2): 182-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Significant differences in the molecular organization of lipid bilayer in remantadin-resistant and remantadin-sensitive strains of influenza virus were demonstrated by means of fluorescent phospholipid probes, analogues of phosphatidylcholine and sphingomyelin. The data on fluorescence polarization and transfer of excitation energy from protein tryptophanes on probe fluorophores showed phosphatidylcholine and sphingomyelin to be segregated in influenza virion membrane. Gradients of mobility of lipid chains in virion membrane and in phospholipid vesicles have opposite directions. The results indicate that M protein coming inside virion into contact with the lipid bilayer does not penetrate further than its middle. In virions of the resistant strain remantadin destroys the array of the entire bilayer whereas in the sensitive strain the addition of remantadin results in a marked decrease of mobility of the chains in the surface area. It is suggested that the molecular organization of lipids is one of the factors determining influenza virus sensitivity to remantadin.

            Descriptors:  adamantane analogs and derivatives, capsid analysis, influenza A virus avian ultrastructure, membrane proteins analysis, rimantadine pharmacology, viral proteins analysis,  drug resistance, microbial, energy transfer, fluorescent dyes analysis, avian drug effects, lipid bilayers analysis, phosphatidylcholines analysis, spectrometry, fluorescence, sphingomyelins analysis.

Moore, J.T., L.M. Spence, T.D. Sanders, and A.K. Adams (1999). Human influenza: viral mutations and altered tropisms. Clinical Laboratory Science Journal of the American Society for Medical Technology 12(2): 67-9.  ISSN: 0894-959X.

            NAL Call Number:  RB37.A1C5

            Abstract:  Influenza is a virus that is capable of causing a pandemic of the human race. Influenza has the ability to infect humans by mutating and altering its pathogenic characteristics. Efforts must be made worldwide to educate people about the possibilities of a potential outbreak. Awareness of optimal conditions which could lead to viral mutation and human to human transmission of a neogenetic strain of influenza appears to be a key deterrent against future cases.

            Descriptors:  influenza genetics, influenza transmission, influenza A virus genetics, mutation, adolescent, adult, birds, child, preschool, disease outbreaks, Hong Kong epidemiology, infant, influenza physiopathology, influenza virology, influenza A virus avian genetics, middle aged, species specificity.

Moran, T.M., H. Park, A. Fernandez Sesma, and J.L. Schulman (1999). Th2 responses to inactivated influenza virus can Be converted to Th1 responses and facilitate recovery from heterosubtypic virus infection. Journal of Infectious Diseases 180(3): 579-85.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Immunization with live influenza virus expands Th1 memory cells and facilitates more rapid recovery after heterosubtypic virus challenge. Immunization with inactivated virus generates a Th2 response and does not lead to heterosubtypic immunity. Creation of a Th1 priming environment by the inclusion of interleukin (IL)-12 with antibodies to IL-4 converted the response against inactivated virus to a Th1 response that was able to facilitate virus clearance upon heterosubtypic virus challenge. Evaluation of memory responses of mice immunized by the various protocols demonstrated that the type of immunization imprints T cell memory, dictating the nature of the response to subsequent infection. After live virus challenge, expansion of Th1 cells seems to facilitate the generation of cytotoxic T lymphocytes from naive precursors. This latter finding may be the mechanism by which inactivated virus immunization in a Th1 cytokine context mediates heterosubtypic immunity.

            Descriptors:  influenza immunology, influenza A virus avian physiology, human physiology, influenza vaccine, Th1 cells immunology, Th2 cells immunology, virus latency physiology, cell line, cytokines biosynthesis, dogs, immunologic memory, avian radiation effects,  human radiation effects, mice, inbred BALB c,  spleen immunology, T lymphocytes, cytotoxic immunology, Th1 cells virology, Th2 cells virology, ultraviolet rays.

Morgan, D.J., C. Kurts, H.T. Kreuwel, K.L. Holst, W.R. Heath, and L.A. Sherman (1999). Ontogeny of T cell tolerance to peripherally expressed antigens. Proceedings of the National Academy of Sciences of the United States of America 96(7): 3854-8.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Transgenic expression of the influenza virus hemagglutinin (HA) in the pancreatic islet beta cells of InsHA mice leads to peripheral tolerance of HA-specific T cells. To examine the onset of tolerance, InsHA mice were immunized with influenza virus A/PR/8 at different ages, and the presence of nontolerant T cells was determined by the induction of autoimmune diabetes. The data revealed a neonatal period wherein T cells were not tolerant and influenza virus infection led to HA-specific beta cell destruction and autoimmune diabetes. The ability to induce autoimmunity gradually waned, such that adult mice were profoundly tolerant to viral HA and were protected from diabetes. Because cross-presentation of islet antigens by professional antigen-presenting cells had been reported to induce peripheral tolerance, the temporal relationship between tolerance induction and activation of HA-specific T cells in the lymph nodes draining the pancreas was examined. In tolerant adult mice, but not in 1-week-old neonates, activation and proliferation of HA-specific CD8(+) T cells occurred in the pancreatic lymph nodes. Thus, lack of tolerance in the perinatal period correlated with lack of activation of antigen-specific CD8(+) T cells. This work provides evidence for the developmental regulation of peripheral tolerance induction.

            Descriptors:  aging immunology, hemagglutinin glycoproteins, influenza virus immunology, influenza A virus immunology, islets of langerhans immunology, receptors, antigen, T cell immunology, T lymphocytes immunology, animals, newborn, diabetes mellitus, type I immunology, diabetes mellitus, type I pathology, hemagglutinin glycoproteins, influenza virus genetics, immune tolerance, influenza A virus avian immunology, islets of langerhans growth and development, islets of langerhans pathology, lymphocyte activation, mice, mice inbred BALB c, mice, transgenic, receptors, antigen, T cell genetics.

Moya, P., M.L. Alonso, E. Baixeras, and E. Ronda (1984). Immunomodulatory activity of isoprinosine on experimental viral infections in avian models. International Journal of Immunopharmacology 6(4): 339-43.  ISSN: 0192-0561.

            NAL Call Number:  QR180.I52

            Abstract:  The immunomodulatory activity of Isoprinosine treatments have been experimentally verified on chicken infected by three different viruses: Newcastle disease, fowl plague and avian infectious bronchitis. In protection tests, positive variations in the mean day of death rather than in the mortality rate were found depending on the modality of treatment. A stimulatory influence on primary anti-Newcastle disease virus antibody response was observed. In the avian model the Isoprinosine antiviral effect appears as due mainly to the enhancement of interferon production and to a synergistic interferon-isoprinosine interaction.

            Descriptors:  adjuvants, immunologic pharmacology, inosine analogs and derivatives, inosine pranobex pharmacology, virus diseases immunology, antibodies, viral biosynthesis, chickens, hemagglutination inhibition tests, infectious bronchitis virus immunology, influenza A virus avian immunology, interferons therapeutic use, kinetics, Newcastle disease virus immunology, vesicular stomatitis Indiana virus immunology, virus diseases drug therapy.

Mucke, K. and C. Scholtissek (1987). Extragenic and intragenic suppression of a transport mutation in the hemagglutinin gene of an influenza A virus as revealed by backcross and sequence determination. Virology 158(1): 112-7.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Cooperation of viral proteins, or functional domains within a protein, can be studied by analyzing temperature-sensitive (ts) mutants and revertants carrying suppressor mutations. Accordingly, we have sequenced the hemagglutinin (HA) genes of a ts mutant of fowl plague virus (FPV), with a transport defect in the HA, and of five independent ts+ revertants (R1, R3, R4, R5, and R9). The amino acid replacement in position 480 from Thr to Ile, leading to the loss of a complex carbohydrate side chain, is responsible for the ts phenotype. R3, R4, and R5 are true revertants in that they have Thr in position 480, while R1 and R9 have kept Ile. The sequence of the HA of R1 is exactly the same as that of the ts mutant, while the R9 HA has two additional amino acid replacements in positions 91 (Lys-Thr) and 104 (Gly-Val). By doing a backcross with wild-type virus, it was shown that R1 carries an extragenic suppressor mutation, while R9 is intragenically suppressed. We conclude that the HA is transported from the site of its synthesis in the rough endoplasmic reticulum (RER) to the plasma membrane along with another viral gene product, which by mutation can complement the ts defect. An alternative interpretation is that the ts mutation results from a change in HA which allows an interacting protein to bind HA too soon, holding it back in the RER. The suppressor mutation may remove this premature interaction.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, suppression, genetic, base sequence, biological transport, cultured cells, crosses, genetic, avian immunology, avian metabolism, mutation, temperature.

Munk, K., E. Pritzer, E. Kretzschmar, B. Gutte, W. Garten, and H.D. Klenk (1992). Carbohydrate masking of an antigenic epitope of influenza virus haemagglutinin independent of oligosaccharide size. Glycobiology 2(3): 233-40.  ISSN: 0959-6658.

            NAL Call Number:  QP552.G59G593

            Abstract:  Comparison of the haemagglutinins (HA) of the pathogenic avian influenza viruses A/FPV/Dutch/27 (H7N7) and A/FPV/Rostock/34 (H7N1) revealed 94.7% nucleotide and 93.8% amino acid sequence homologies. Six of the seven N-glycosidic oligosaccharides of the Rostock HA are at the same positions as the six carbohydrates of the Dutch strain. The additional oligosaccharide side chain of the Rostock strain, which is of the complex type, is attached to asparagine149 in antigenic epitope B. The accessibility of this antigenic epitope has been analysed by using rabbit antisera raised against synthetic peptides comprising amino acids 143-162. The carbohydrates of the HA of the Rostock strain have been modified (i) to truncated cores by expression in insect cells using a baculovirus vector, (ii) to oligomannosidic side chains by growth in the presence of the trimming inhibitor methyldeoxynojirimycin and (iii) to a single N-acetylglucosamine residue by removal of the oligomannosidic sugar with endo-beta-N-acetylglucosaminidase H. Neither the authentic nor the modified oligosaccharides allowed antibody binding, as indicated by enzyme-linked immunosorbent assay (ELISA) and Western blot analyses. Reactivity was observed, however, after complete removal of the carbohydrate from HA of the Rostock strain by digestion with peptide-N-glycosidase F. HA of the Dutch strain was reactive without prior peptide-N-glycosidase F treatment. These results demonstrate that a single N-acetyl-glucosamine at asparagine149 is sufficient to prevent recognition of the peptide epitope.

            Descriptors:  hemagglutinins viral chemistry, influenza A virus avian chemistry, avian immunology, oligosaccharides chemistry, oligosaccharides immunology, amino acid sequence, antigens, viral chemistry, epitopes chemistry, hemagglutinins viral immunology, models, molecular, molecular conformation, molecular sequence data, sequence homology, nucleic acid, species specificity.

Murakami, M., T. Towatari, M. Ohuchi, M. Shiota, M. Akao, Y. Okumura, M.A. Parry, and H. Kido (2001). Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus. European Journal of Biochemistry FEBS 268(10):  2847-55.  ISSN: 0014-2956.

            NAL Call Number:  QP501.E8

            Abstract:  Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. Here we report a protease present in the airway that, like tryptase Clara, can process influenza A virus haemagglutinin and Sendai virus envelope fusion glycoprotein. This protease was extracted from the membrane fraction of rat lungs, purified and then identified as a mini-plasmin. Mini-plasmin was distributed predominantly in the epithelial cells of the upward divisions of bronchioles and potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. In comparison with plasmin, its increased hydrophobicity, leading to its higher local concentrations on membranes, and decreased molecular mass may enable mini-plasmin to gain ready access to the cleavage sites of various haemagglutinins and fusion glycoproteins after expression of these viral proteins on the cell surface. These findings suggest that mini-plasmin in the airway may play a pivotal role in the spread of viruses and their pathogenicity.

            Descriptors:  bronchi cytology, epithelial cells chemistry, infection, influenza A virus metabolism, peptide fragments chemistry, plasmin chemistry, respirovirus metabolism, amino acid sequence, blotting, western, bronchi metabolism, bronchi pathology, bronchi virology, cell membrane metabolism, dose response relationship, drug, electrophoresis, polyacrylamide gel, immunohistochemistry, isoflurophate pharmacology, lung metabolism, lung pathology, lung virology, molecular sequence data, rats, rats, wistar, sequence analysis, protein, sequence homology, amino acid, substrate specificity, viral envelope proteins chemistry, viral envelope proteins metabolism.

Murakami, Y., K. Nerome, Y. Yoshioka, S. Mizuno, and A. Oya (1988). Difference in growth behavior of human, swine, equine, and avian influenza viruses at a high temperature. Archives of Virology 100(3-4): 231-44.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Growth characteristics of a wide range of influenza A viruses from different mammals and bird species were examined in an established line of canine kidney (MDCK) cells at an ordinary (37 degrees C) and a high temperature (42 degrees C). Although all viruses employed in the present study possessed a capability of replicating at 37 degrees C, virus growth at 42 degrees C showed considerable variation and reflected differences in the natural hosts of the isolates. All reference strains and isolates from bird species grew well in the MDCK cells maintained at 42 degrees C, but human viruses did not, showing an asymmetrical growth behavior. In contrast to this, growth of swine and equine viruses showed growth characteristics intermediate between human and avian viruses. Of the two swine viruses examined, replication of one strain occurred equally well at both temperatures and another failed to grow at 42 degrees C. Similarly, two of the three equine viruses tested belonging to H3N8 antigenic subtypes grew at 42 degrees C. However, the results obtained from comparison of plaque sizes and growth curves indicated that the replication of the above swine and equine viruses was restricted under a stringent temperature when compared to avian viruses. The detailed analysis of cloned viruses revealed that some of the swine and equine viruses contained two variants which are readily distinguished by growth behavior at 42 degrees C. Genome analysis of parental and virus clones by oligonucleotide mapping and migration profiles of RNA segments did not detect any differences among the above variants exhibiting the asymmetrical growth characteristics at 42 degrees C.

            Descriptors:  influenza A virus avian growth and development, human growth and development, influenza A virus growth and development, cell line, genes viral, horses, avian genetics, human genetics, porcine genetics, porcine growth and development, influenza A virus genetics, plaque assay, RNA viral genetics, temperature.

Murphy, B.R., A.J. Buckler White, W.T. London, J. Harper, E.L. Tierney, N.T. Miller, L.J. Reck, R.M. Chanock, and V.S. Hinshaw (1984). Avian-human reassortant influenza A viruses derived by mating avian and human influenza A viruses.  Journal of Infectious Diseases 150(6): 841-50.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Reassortant influenza A viruses were produced by mating an avian virus (A/Mallard/NY/78, A/Mallard/Alberta/78, or A/Pintail/Alberta/79) with a wild-type human influenza A virus. From each mating a reassortant virus was obtained that contained the genes coding for the hemagglutinin and neuraminidase surface antigens of the human influenza A wild-type virus and the six other RNA segments ("internal genes") of the avian influenza A virus parent. The avian-human reassortant influenza viruses produced resembled their avian virus parent in that they produced plaques on MDCK monolayers at 42 C, a temperature restrictive for the human influenza viruses. In the trachea of squirrel monkeys, each avian-human reassortant influenza virus was as restricted in its replication as was its avian influenza virus parent. Thus, one or more of the six internal genes of each avian parent virus was responsible for restriction of the reassortant virus in monkeys. The A/Washington/80 X A/Mallard/NY/78 reassortant virus retained its phenotype of restricted replication in monkeys after five serial passages in vivo. It also failed to transmit to cagemates or induce resistance to wild-type virus challenge, and it did not initiate a systemic or enteric infection. These findings form the basis for evaluation of these attenuated avian-human reassortant influenza A viruses as live attenuated vaccines for humans.

            Descriptors:  crosses, genetic, influenza A virus avian genetics, human genetics, neuraminidase genetics, chickens, child, ducks, hemagglutinins viral genetics, immunization, avian physiology, human physiology, saimiri, virus replication.

Murphy, B.R., A.J. Buckler White, W.T. London, and M.H. Snyder (1989). Characterization of the M protein and nucleoprotein genes of an avian influenza A virus which are involved in host range restriction in monkeys. Vaccine 7(6): 557-61.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  A reassortant virus possessing RNA segment 7, which codes for the M1 and M2 proteins, of the avian influenza A/Mallard/New York/6750/78 (H2N2) virus and the other seven RNA segments of the human influenza A/Udorn/307/72 (H3N2) virus had been shown previously to be markedly restricted in replication in the respiratory tract of squirrel monkeys. In contrast, a reassortant possessing segment 7 of another avian influenza virus, A/Pintail/Alberta/119/79 (H4N6), and the seven other RNA segments from the A/Udorn/72 virus was not restricted. The nucleotide and deduced amino acid sequence of the RNA segment 7 of each virus was determined to identify the structural basis for the attenuation phenotype specified by RNA segment 7 of the A/Mallard/78 virus. Analysis of the deduced amino acid sequences revealed only two amino acid differences in the M1 protein and one difference in the M2 protein, suggesting that the attenuation phenotype of a reassortant virus possessing segment 7 of the A/Mallard/78 virus may be specified by one to three amino acids. Reassortant viruses possessing RNA segment 6, which codes for the nucleoprotein, of either avian influenza virus and the other seven RNA segments of a human influenza virus were also restricted in replication in squirrel monkeys. A comparison of the deduced amino acid sequences of the two avian nucleopeoteins demonstrated only three amino acid differences indicating that these two avian viruses possess NP genes that are highly related. The high degree of relatedness of both the NP and M proteins of these two avian viruses contrasts with their divergent surface antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

            Descriptors:  genes viral, influenza A virus avian genetics, nucleoproteins genetics, viral core proteins, viral matrix proteins genetics, viral proteins genetics, amino acid sequence, base sequence, human genetics, RNA viral analysis, saimiri, virus replication.

Murphy, B.R., M.L. Clements, E.L. Tierney, R.E. Black, J. Stienberg, and R.M. Chanock (1985). Dose response of influenza A/Washington/897/80 (H3N2) avian-human reassortant virus in adult volunteers. Journal of Infectious Diseases 152(1): 225-9.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  antibodies, viral biosynthesis, influenza A virus avian immunology, human immunology, influenza vaccine immunology, adult, dose response relationship, immunologic, influenza microbiology, influenza transmission, avian genetics, human genetics, recombination, genetic, vaccination, vaccines, attenuated.

Murphy, B.R., D.L. Sly, E.L. Tierney, N.T. Hosier, J.G. Massicot, W.T. London, R.M. Chanock, R.G. Webster, and V.S. Hinshaw (1982). Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys. Science 218(4579): 1330-2.  ISSN: 0036-8075.

            NAL Call Number:  470 Sci2

            Abstract:  An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication is squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistant to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.

            Descriptors:  influenza A virus avian genetics, human genetics, influenza vaccine immunology, antigens, surface genetics, epitopes genetics, epitopes immunology, hamsters, hemagglutinins genetics, hemagglutinins immunology, neuraminidase genetics, neuraminidase immunology, saimiri, vaccines, attenuated immunology.

Naeve, C.W., V.S. Hinshaw, and R.G. Webster (1984). Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. Journal of Virology  51(2): 567-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Avian influenza virus reassortants containing human influenza virus hemagglutinins do not replicate in ducks. Two mutations in the receptor-binding site of a human hemagglutinin at residues 226 and 228 allowed replication in ducks. The mutations resulted in a receptor-binding-site sequence identical to the known avian influenza virus sequences.

            Descriptors:  influenza A virus avian genetics, human genetics, mutation, receptors, immunologic genetics, base sequence, DNA replication, ducks, genes viral, avian immunology, human immunology, species specificity, virus replication.

Naeve, C.W. and R.G. Webster (1983). Sequence of the hemagglutinin gene from influenza virus A/Seal/Mass/1/80. Virology 129(2): 298-308.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  A double-strand DNA copy of the influenza virus A/Seal/Mass/1/80 (H7N7) [seal] hemagglutinin (HA) gene was cloned into the plasmid pAT153/PvuII/8 and sequenced to deduce the primary amino acid sequence. The gene is 1731 nucleotides long and codes for a protein of 560 amino acids with a nonglycosylated molecular weight of 62098 Da. The deduced amino acid sequence displays similarities to all other sequenced hemagglutinins by retaining six of seven potential glycosylation sites, showing conversation in the number and position of cysteine residues, conservation in the fusion and anchor peptides, and conservation in the putative receptor site of the molecule. However, three features of the primary amino acid sequence could be distinguished from the H7 amino acid sequence of A/fowl plague/Rostock/34 (FPV), another avian H7 influenza virus which does not produce disease in mammals. First, the seal HA sequence has three fewer amino acids in the connecting peptide region of the HA than FPV. This lack of multiple basic amino acids in the connecting peptide is similar to that found in avirulent H7 avian strains and to mammalian serotypes H1, H2, and H3. Second, the seal HA has gained four additional proline residues, all in HA1, as compared to FPV. These residues may alter the tertiary structure of the HA and ultimately contribute to the biological features of this virus. Third, the seal HA has lost a potential carbohydrate attachment site at residue 149 which lies at the tip of the HA structure. The loss of this carbohydrate could alter the seal HAs interaction with host cell receptors.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus genetics, amino acid sequence, base sequence, chemistry, DNA,  hemagglutinins viral analysis, influenza A virus avian genetics, influenza A virus immunology, proline analysis, protein conformation, structure activity relationship.

Naeve, C.W., R.G. Webster, and V.S. Hinshaw (1983). Phenotypic variation in influenza virus reassortants with identical gene constellations. Virology 128(2): 331-40.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  To determine which gene segments of influenza A viruses are responsible for the property of tissue tropism, reassortants were produced between the avian influenza strain, A/Mal/NY/6750/78 [H2N2] (Mal/NY), and a human strain, A/Udorn/307/72 [H3N2] (Udorn). The avian strain replicates in the intestinal tract of ducks and the human strain does not. Eight reassortants were shown by hybridization analysis to have the same gene constellation, having received hemagglutinin gene segment 4 from Udorn and the remaining seven gene segments from Mal/NY. With one exception, all reassortants containing the Udorn HA were restricted in their ability to traverse the digestive tract of ducks and replicate therein. The exception, reassortant R2, replicated to high titers in the intestinal tract. The R2 virus was shown to possess a hemagglutinin molecule that was antigenically distinguishable from the Udorn parent with polyclonal and monoclonal antibodies. The virus was "nonavid" in reaction with antihemagglutinin antibodies and was phenotypically similar to avian influenza viruses. The results suggest that the R2 hemagglutinin has undergone mutation(s) altering tissue tropism and antigenic properties of the virus. These studies illustrate the importance of the hemagglutinin gene in determining tissue tropism and present an example of phenotypic variation in a virus population with the same gene constellation but do not exclude a requirement for other gene products.

            Descriptors:  ducks microbiology, genes viral, influenza A virus avian genetics, influenza A virus human genetics, virus replication, hemagglutinins viral genetics, hemagglutinins viral immunology, influenza A virus avian immunology, influenza A virus avian physiology, influenza A virus human immunology, influenza A virus human physiology, intestines microbiology, nucleic acid hybridization, recombination, genetic.

Naffakh, N., P. Massin, N. Escriou, B. Crescenzo Chaigne, and S. van der Werf (2000). Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses. Journal of General Virology 81(Pt. 5): 1283-91.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  In order to determine how efficiently the polymerase proteins derived from human and avian influenza A viruses can interact with each other in the context of a mammalian cell, a genetic system that allows the in vivo reconstitution of active ribonucleoproteins was used. The ability to achieve replication of a viral-like reporter RNA in COS-1 cells was examined with heterospecific mixtures of the core proteins (PB1, PB2, PA and NP) from two strains of human viruses (A/Puerto Rico/8/34 and A/Victoria/3/75), two strains of avian viruses (A/Mallard/NY/6750/78 and A/FPV/-Rostock/34), and a strain of avian origin (A/Hong Kong/156/97) that was isolated from the first human case of H5N1 influenza in Hong Kong in 1997. In accordance with published observations on reassortant viruses, PB2 amino acid 627 was identified as a major determinant of the replication efficiency of heterospecific complexes in COS-1 cells. Moreover, the results showed that replication of the viral-like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins. Furthermore, the PB1 and PB2 proteins from the A/Hong- Kong/156/97 virus exhibited intermediate properties with respect to the corresponding proteins from avian or human influenza viruses, suggesting that some molecular characteristics of PB1 and PB2 proteins might at least partially account for the ability of the A/Hong Kong/156/97 virus to replicate in humans.

            Descriptors:  influenza A virus avian genetics, influenza A virus human genetics, nucleoproteins, RNA replicase, viral core proteins genetics, viral core proteins metabolism, cos cells, chloramphenicol o acetyltransferase, cloning, molecular, DNA, complementary, DNA directed RNA polymerases genetics, DNA directed RNA polymerases metabolism, influenza A virus avian metabolism, influenza A virus human metabolism, molecular sequence data, plasmids genetics, sequence analysis, DNA, transcription, genetic, transfection, viral proteins genetics, viral proteins metabolism, virus replication.

Nakajima, K., E. Nobusawa, and S. Nakajima (1990). Evolution of the NS genes of the influenza A viruses. II. Characteristics of the amino acid changes in the NS1 proteins of the influenza A viruses. Virus Genes 4(1): 15-26.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  We compared the amino acid sequences of the NS1 proteins of human, equine, and avian influenza viruses. The ratios of the amino acid substitutions per nucleotide substitutions in the NS1 proteins were about 27-45%, suggesting the existence of constraints on the amino acid changes of the NS1 protein in evolution. As a measure of constraints exerted on the regions of a protein, a changeability index is proposed. There was a highly conserved region between amino acid residues 30 and 50. The C-terminal region of amino acid residue 165 was a continuously changeable region. We have either introduced several nucleotide substitutions to the NS cDNA of the A/Udorn/72 virus in vitro or constructed the recombinant NS cDNAs between the A/Udorn/72 and A/chick/Japan/24 viruses, and then expressed them in animal cells. We have found that the amino acid substitutions introduced to the low-conserved region of the NS1 protein affected the stability and nuclear localization of the NS1 protein. One of the chimeric proteins between the A/Udorn/72 and A/chick/Japan/24 viruses did not move to the nucleus of the cell and remained in the cytoplasm.

            Descriptors:  capsid genetics, evolution, genes viral, influenza A virus genetics, viral core proteins genetics, amino acid sequence, base sequence, birds, chimera, cytoplasm ultrastructure, DNA, viral analysis, fluorescent antibody technique, horses, molecular sequence data, mutation, structure activity relationship, viral nonstructural proteins.

Nakajima, K., E. Nobusawa, and S. Nakajima (1984). Genetic relatedness between A/Swine/Iowa/15/30(H1N1) and human influenza viruses. Virology 139(1): 194-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The nucleotide sequences of the M and NS1 genes of influenza virus A/Swine/Iowa/15/30 (A/SW/IW/30)(H1N1) were determined with cloned DNAs and compared with reported sequences of human and avian influenza viruses. A/SW/IW/30 virus was found to be closely similar to A/PR/8/34(H1N1) virus in the nucleotide sequences of the M and NS1 genes, the base differences between the two strains being 64 out of 1027 nucleotides in the M gene and 52 out of 740 in the NS1 gene. Based on the assumptions that these two viruses were derived from a common ancestor and that the rate of base changes per year was the same in man and in swine, it was estimated that the progenitor virus was in circulation during the period from 1915 to 1920. This estimation was compatible with the epidemiological findings suggesting that the progenitor of the swine influenza virus was the agent of the 1918 influenza pandemic. Furthermore, the M and NS1 gene sequences of A/FPV/Rostock/34(H7N6) virus were much closer to those of A/SW/IW/30 and A/PR/8/34 viruses than to A/duck/Alberta/60/76(H12N5) virus, but not as close as the A/SW/IW/30 virus was to A/PR/8/34 virus.

            Descriptors:  influenza A virus human genetics, influenza A virus, porcine genetics, influenza A virus genetics, base sequence, evolution, genes viral.

Nakajima, K., E. Nobusawa, T. Ogawa, and S. Nakajima (1990). Evolution of the NS genes of the influenza A viruses. I. The genetic relatedness of the NS genes of animal influenza viruses.  Virus Genes 4(1): 5-13.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  We compared the nucleotide sequences of the NS genes of 13 animal influenza viruses belonging to human, swine, avian, and equine viruses for the study of the genetic relatedness of the NS genes in animal influenza viruses. The NS genes of three virus strains A/chicken/Brescia/02, A/equine/Prague/56, and A/equine/Miami/63 were newly sequenced. The base sequence homologies between the NS genes of avian, human, swine, and the A/equine/Miami/63 viruses were 87.8% or higher. On the other hand, the base sequence of the NS gene of the A/equine/Prague/56 virus differed widely from those of other viruses analyzed in the present study. We constructed a model of the genetic tree of the NS genes of avian and equine influenza viruses by a modified Farris method. For comparison of the NS genes between human and avian viruses, we estimated the speed of the nucleotide substitutions of the avian influenza NS genes. It was roughly constant, even though the substitutions did not occur sequentially. The nucleotide substitution rate of the NS genes of avian influenza viruses was one-third to one-fourth that of human influenza viruses. We deduced the time of separation between the NS genes of human and avian influenza viruses during evolution.

            Descriptors:  base sequence, capsid genetics, evolution, genes viral, influenza A virus genetics, sequence homology, nucleic acid, viral core proteins genetics, DNA, viral analysis, molecular sequence data, viral nonstructural proteins.

Nakajima, K., E. Nobusawa, T. Ogawa, and S. Nakajima (1987). Genetic divergence of the NS genes of avian influenza viruses. Virology 158(2): 465-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The nucleotide sequences of the NS genes of avian influenza A viruses, A/Chicken/Japan/24, A/Duck/England/56, A/Tern/South Africa/61, A/Duck/Ukraine/1/63, and A/Mynah/Haneda-Thai/76, were determined and compared among themselves and with two reported NS sequences of the avian viruses, A/FPV/Rostock/34 and A/Duck/Alberta/60/76. Thirty-six to two hundred forty base differences in the NS genes were found in pairwise comparisons among the viruses. The numbers of base differences in the NS genes increased with time, except A/Duck/Alberta/60/76 virus. However, the NS genes of the avian viruses did not change sequentially with time and were arranged in separate evolutionary lineages. When the NS genes of avian viruses employed in the present study were compared with those of human viruses, sequence similarity was confirmed (M. Baez, R. Taussig, J. J. Zarza, J. F. Young, P. Palese, A. Reisfield, and A. M. Skalka, 1980, Nucleic Acids Res. 8, 5845-5858). The numbers of base differences in the NS genes between avian viruses and the A/PR/8/34 virus were 61 to 83, and the NS gene of the oldest avian isolate, A/Chicken/Japan/24, was most closely related to that of the A/PR/8/34 virus. It was hypothesized that NS genes of human influenza viruses and those of some avian influenza viruses had been derived from a common ancestor gene.

            Descriptors:  antigens, viral genetics, influenza A virus immunology, viral proteins genetics, base sequence, influenza A virus genetics, variation genetics, viral nonstructural proteins.

Naruse, H., C. Scholtissek, and H.D. Klenk (1986). Temperature-sensitive mutants of fowl plague virus defective in the intracellular transport of the hemagglutinin. Virus Research 5(2-3): 293-305.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Nine mutants of fowl plague virus with temperature-sensitive defects in the biosynthesis of the hemagglutinin have been characterized by analyzing the processing and the intracellular location of this glycoprotein in MDCK and chick embryo cells. It was found that with all of these mutants the transport of the hemagglutinin to the cell surface was impeded at the non-permissive temperature. There were differences, however, in the site of the block. With mutants tsl, ts227, ts478 and ts658 the precursor HA was not cleaved and the oligosaccharide side chains remained sensitive to endoglucosaminidase H. When the hemagglutinin was analyzed in permeabilized cells by immunofluorescence, usually only cytoplasmic labeling was seen. Immunofluorescence of non-permeabilized cells and hemadsorption revealed that the hemagglutinin did not reach the cell surface. In contrast, the hemagglutinin of mutants ts79, ts482, ts532, ts546 and ts651 was cleaved and oligosaccharides were processed to the endoglucosaminidase H-resistant form at non-permissive temperature. In permeabilized cells, the cytoplasm and juxtanuclear regions typical for the Golgi apparatus were labeled by immunofluorescence. Except for ts482, ts532 and ts546 which were leaky, hemagglutinin could not be detected at the cell surface. These observations indicate that, with the first group of mutants, hemagglutinin transport is usually arrested already in the rough endoplasmic reticulum, whereas with the second group it is inhibited at a late stage between the Golgi apparatus and the plasma membrane.

            Descriptors:  defective viruses genetics, hemagglutinins viral, influenza A virus avian genetics, mutation, cell line, chick embryo, defective viruses growth and development, hemagglutination, influenza A virus avian growth and development, temperature.

Neighbor, N.K., L.A. Newberry, G.R. Bayyari, J.K. Skeeles, J.N. Beasley, and R.W. McNew (1994). The effect of microaerosolized hydrogen peroxide on bacterial and viral poultry pathogens. Poultry Science (USA) 73(10): 1511-1516.  ISSN: 0032-5791.

            NAL Call Number:  47.8 Am33P

            Abstract:  The effect of microaerosolized H2O2 on bacterial and viral poultry pathogens was investigated. Bacterial cultures and viruses were dried on sterile glass Petri dishes and subjected to direct and indirect 5% (H2O2) microaerosol mist. In the trials using Escherichia coli and Staphylococcus aureus, there was complete inactivation following exposure to H2O2. Using Salmonella typhimurium, indirect exposure resulted in only partial inactivation whereas direct exposure to H2O2 gave complete inactivation. For the viruses studied, 5% H2O2 microaerosol mist completely inactivated infectious laryngotracheitis virus. Newcastle disease virus, infectious bronchitis virus, and avian influenza virus showed reduced infectivity but were not completely inactivated. Avian reovirus susceptibility varied with the method of exposure and infectious bursal disease virus was highly resistant. The use of 10% H2O2 mist, however, resulted in total inactivation of infectious bursal disease virus. The effect of 10% H2O2 on equipment and selected materials representative of a hatcher or poultry house was investigated. A solar cell calculator, a thermostat containing a microswitch, and samples of uncoated steel, galvanized steel, and uncoated aluminum were subjected to 10 fumigation cycles. No damage was detected in the calculator and the thermostat. Both the uncoated steel and the galvanized steel showed signs of oxidation. The aluminum did not show signs of oxidation.

            Descriptors:  aerosols, fumigation, hydrogen peroxide, cell counting, bacteria, pathogens, avian infectious bronchitis virus, avian laryngotracheitis virus, avian influenza virus, Newcastle disease virus, Salmonella typhimurium, Staphylococcus aureus, Escherichia coli, reoviridae, avian infectious bursitis, corrosion, application methods, bacteria, biological analysis, colloids, coronaviridae, deterioration, dispersions, enterobacteriaceae, Escherichia, herpetoviridae, infectious diseases, influenza virus, micrococcaceae, oxides, paramyxoviridae, peroxides, physical states, Salmonella, Staphylococcus, viroses, viruses,  inactivation, avian reovirus, infectious bursal disease virus.

Nerome, K., Y. Yoshioka, S. Sakamoto, H. Yasuhara, and A. Oya (1985). Characterization of a 1980-swine recombinant influenza virus possessing H1 hemagglutinin and N2 neuraminidase similar to that of the earliest Hong Kong (H3N2) virus. Archives of Virology 86(3-4): 197-211.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A recombinant (H1N2, formerly Hsw 1N2), A/swine/Ehime/1/80 was found to possess antigenic, biological and genomic characteristics different from those of a previous A/swine/Kanagawa/2/78 (H1N2) strain. Five monoclonal antibodies to A/NJ/8/76 definitely differentiated the hemagglutinin molecules of the former virus from the latter, showing that these viruses differed, at least, at two antigenic determinants. Neuraminidase-inhibition tests with monoclonal antibodies to different H2N2 and H3N2 viruses revealed that the A/swine/Ehime/1/80 strain contained a neuraminidase very similar to that of the late human Asian (H2N2) and the earliest Hong Kong (H3N2) viruses. Growth comparison of swine and human isolates indicated that A/swine/Ehime/1/80 and A/swine/Shizuoka/1/78 (H1N1) failed to grow at 42 degrees C, while A/swine/Kanagawa/2/78 and its possible parental virus, A/swine/Kanagawa/4/78 (H1N1) replicated efficiently at this stringent temperature. These results revealed that the viruses having growth characteristics similar to those of avian influenza virus were present in the swine population. RNA analysis by oligonucleotide mapping suggested that A/swine/Ehime/1/80 may be a recombinant between A/swine/Shizuoka/1/78-like and A/Aichi/2/68 (H3N2)-like viruses. To further determine the gene constellation of this recombinant virus, DNA-RNA hybridization was performed by using DNA segments complementary for swine (H1N1) virus RNA and the entire RNAs of three viruses. The molecular hybridization could define the genomic composition of the recombinant, indicating that only the neuraminidase gene of this virus is derived from the earliest Hong Kong (H3N2)-like virus and remaining seven genes from swine (H1N1) virus.

            Descriptors:  hemagglutinins viral analysis, influenza A virus human immunology, influenza A virus, porcine immunology, influenza A virus immunology, neuraminidase analysis, hemagglutination, viral, influenza A virus human enzymology, influenza A virus, porcine enzymology, influenza A virus, porcine genetics, nucleic acid hybridization, oligonucleotides analysis, RNA viral analysis, recombination, genetic, swine, temperature, virus replication.

Nerome, K., Y. Yoshioka, C.A. Torres, A. Oya, P. Bachmann, K. Ottis, and R.G. Webster (1984). Persistence of Q strain of H2N2 influenza virus in avian species: antigenic, biological and genetic analysis of avian and human H2N2 viruses. Archives of Virology 81(3-4): 239-50.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The characteristics of an avian influenza virus were compared in detail with those of human Asian (H2N2) influenza viruses. Antigenic analysis by different antisera against H2N2 viruses and monoclonal antibodies to both the hemagglutinin and neuraminidase antigens showed that an avian isolate, A/duck/Munchen/9/79 contained hemagglutinin and neuraminidase subunits closely related to those of the early human H2N2 viruses which had been prevalent in 1957. However, this avian virus gave low HI titers with absorbed and non-absorbed antisera to different human H2N2 viruses isolated in 1957. Like human Q phase variant, such as A/RI/5-/57 (H2N2), hemagglutination of the above avian strain was not inhibited by the purified non-specific gamma-inhibitor from guinea pig serum. Growth behavior at restrictive temperature (42 degrees C) clearly differentiate the avian H2N2 virus from human influenza viruses, showing that the former virus grew well in MDCK cells at 42 degrees C but not the latters. Genomic analysis of these viruses revealed that the oligonucleotide map of H2N2 virus isolated from a duck was quite different from those of human H2N2 viruses from 1957 to 1967. The oligonucleotide mapping also indicated that different H2N2 influenza virus variants had co-circulated in humans in 1957.

            Descriptors:  influenza A virus avian immunology, influenza A virus human immunology, hemagglutinins viral immunology, influenza A virus avian genetics, influenza A virus human genetics, influenza A virus growth and development, neuraminidase immunology, RNA viral genetics.

Nestorowicz, A., Y. Kawaoka, W.J. Bean, and R.G. Webster (1987). Molecular analysis of the hemagglutinin genes of Australian H7N7 influenza viruses: role of passerine birds in maintenance or transmission? Virology 160(2): 411-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  In 1985 a fowl plague-like disease occurred in chickens in Lockwood, Victoria, Australia and caused high mortality. An H7N7 influenza virus was isolated from the chickens (A/Chicken/Victoria/1/85); additionally, an antigenically similar virus was isolated from starlings (A/Starling/Victoria/5156/85) and serological evidence of H7N7 virus infection was found in sparrows. Antigenic analysis with monoclonal antibodies to H7, oligonucleotide mapping of total vRNA, and sequence analysis of the HA genes established that the chicken and starling influenza viruses were closely related and probably came from the same source. There was high nucleotide sequence homology (95.3%) between the HA genes of A/Chick/Vic/85 and a fowl plague-like virus isolated from chickens in Victoria 9 years earlier [A/Fowl/Vic/76 (H7N7)]. The sequence homologies indicated that the A/Chick/Vic/85 and A/Fowl/Vic/76 were derived from a common recent ancestor, while another recent H7N7 virus, Seal/Mass/1/80 originated from a different evolutionary lineage. Experimental infection of chickens and starlings with A/Chick/Vic/1/85 (H7N7) was associated with high mortality (100%), transmission to contact birds of the same species, and virus in all organs. In sparrows one-third of the birds died after infection and virus was isolated from most organs; transmission to contact sparrows did not occur. In contrast, the H7N7 virus replicated in ducks and spread to contact ducks but caused no mortality. These studies establish that the host species plays a role in determining the virulence of avian influenza viruses, and provide the first evidence for transmission of virulent influenza viruses between domestic poultry and passerine birds. They support the hypothesis that potentially virulent H7N7 influenza viruses could be maintained in ducks where they cause no apparent disease and may sometimes spread to other wild birds and domestic poultry.

            Descriptors:  birds microbiology, hemagglutinins viral genetics, influenza A virus avian genetics, amino acid sequence, animals, wild microbiology, Australia, base sequence, chickens microbiology, disease reservoirs, genes viral, molecular sequence data, nucleotide mapping, RNA viral genetics, species specificity, virus replication.

Netesov, S.V., S.I.A. Golovin, I.V. Frolov, T.P. Mikriukova, and P.F. Safronov (1989). Pervichnaia struktura gena gemaggliutinina virusa grippa ptits A/FPV/Weybridge. [Primary structure of the avian influenza virus A/FVP/Weybridge hemagglutinin gene]. Molekuliarnaia Genetika, Mikrobiologiia i Virusologiia (5): 26-34.  ISSN: 0208-0613.

            NAL Call Number:  QH506.M65F2

            Abstract:  The complete primary structure of cDNA for hemagglutinin gene of influenza virus A/FPV/weybridge/27 subtype H7 has been determined. Its comparison with the structures of analogous genes from other strains of the same subtype has shown 75% of base changes resulting in silent mutations. This suggests the weak immunological pressing in course of evolution of this subtype strains. The reason for apathogenicity of this avian strain is supposed to be elimination of a glycosylation site present in the strain A/FPV/Rostock/34. The possibility of using the obtained data for construction of the new generation of vaccines is discussed.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, amino acid sequence, base sequence, molecular sequence data.

Neumann, G., M. Hatta, and Y. Kawaoka (2003). Reverse genetics for the control of avian influenza. Avian Diseases 47(Special Issue): 882-887.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Avian influenza viruses are major contributors to viral disease in poultry as well as humans. Outbreaks of high-pathogenicity avian influenza viruses cause high mortality in poultry, resulting in significant economic losses. The potential of avian influenza viruses to reassort with human strains resulted in global pandemics in 1957 and 1968, while the introduction of an entirely avian virus into humans claimed several lives in Hong Kong in 1997. Despite considerable research, the mechanisms that determine the pathogenic potential of a virus or its ability to cross the species barrier are poorly understood. Reverse genetics methods, i.e., methods that allow the generation of an influenza virus entirely from cloned cDNAs, have provided us with one means to address these issues. In addition, reverse genetics is an excellent tool for vaccine production and development. This technology should increase our preparedness for future influenza virus outbreaks.

            Descriptors:  epidemiology, infection, molecular genetics, avian influenza, genetics, infectious disease, prevention and control, respiratory system disease, viral disease, disease control, economic losses, global pandemics, reverse genetics, viral outbreaks, viral pathogenicity.

Neumann, G., T. Watanabe, H. Ito, S. Watanabe, H. Goto, P. Gao, M. Hughes, D.R. Perez, R. Donis, E. Hoffmann, G. Hobom, and Y. Kawaoka (1999). Generation of influenza A viruses entirely from cloned cDNAs. Proceedings of the National Academy of Sciences of the United States of America 96(16): 9345-50.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  We describe a new reverse-genetics system that allows one to efficiently generate influenza A viruses entirely from cloned cDNAs. Human embryonic kidney cells (293T) were transfected with eight plasmids, each encoding a viral RNA of the A/WSN/33 (H1N1) or A/PR/8/34 (H1N1) virus, flanked by the human RNA polymerase I promoter and the mouse RNA polymerase I terminator-together with plasmids encoding viral nucleoprotein and the PB2, PB1, and PA viral polymerases. This strategy yielded >1 x 10(3) plaque-forming units (pfu) of virus per ml of supernatant at 48 hr posttransfection. The addition of plasmids expressing all of the remaining viral structural proteins led to a substantial increase in virus production, 3 x 10(4)-5 x 10(7) pfu/ml. We also used reverse genetics to generate a reassortant virus containing the PB1 gene of the A/PR/8/34 virus, with all other genes representing A/WSN/33. Additional viruses produced by this method had mutations in the PA gene or possessed a foreign epitope in the head of the neuraminidase protein. This efficient system, which does not require helper virus infection, should be useful in viral mutagenesis studies and in the production of vaccines and gene therapy vectors.

            Descriptors:  DNA, complementary, DNA, viral genetics, influenza A virus genetics, RNA viral genetics, cell line, chick embryo, dogs, hn protein genetics, influenza A virus avian genetics, influenza A virus human genetics, influenza A virus physiology, kidney, mice, plasmids, RNA polymerase I metabolism, reverse transcriptase polymerase chain reaction, transfection, viral structural proteins genetics, virus replication.

Neykova, N., D. Simov, G. Galunska, E. Velichkova, A.S. Galabov, and A. Karparov (1981). Benzoxazolone-5-sulphonanilides, 1-(benzoxazolone-5'-sulphonyl)-benzotriazoles and 4-hydroxy-3,2'-diaminobenzenesulphonanilides with antiviral activity. Arzneimittel Forschung 31(5): 747-52.  ISSN: 0004-4172.

            NAL Call Number:  RS1.A7

            Abstract:  benzoxazolone-5-(2'-nitro)-sulphonanilides were synthesized by acylation of o-nitroanilines with benzoxazolone-5-sulphochloride or 3-methylbenzoxazolone-5-sulphochloride. The nitro group in these compounds was subjected to reduction and the resulting amino derivatives were cyclysed to yield the corresponding 1-(benzoxazolone-5'-sulphonyl)-benzotriazoles. Decyclization of the oxazolone cycle of benzoxazolone-5-(2'-amino)-sulphonanilides resulted in 4-hydroxy-3,2'-diaminobenzenesulphonanilides. In vitro testing of the antiviral activity of the compounds obtained during successive synthetic steps revealed that some of them exhibited marked antiviral effect against toga, orthomixo, oncorna and herpes viruses.

            Descriptors:  antiviral agents chemical synthesis, benzoxazoles chemical synthesis, sulfanilamides chemical synthesis, antiviral agents pharmacology, benzoxazoles pharmacology, chemistry, cytopathogenic effect, viral drug effects, herpesvirus 1, suid drug effects, influenza A virus avian drug effects, mice, mice inbred BALB c, moloney murine leukemia virus drug effects, Semliki Forest virus drug effects, sulfanilamides pharmacology, triazoles chemical synthesis, triazoles pharmacology.

Nichol, S.T., C.R. Penn, and B.W. Mahy (1981). Evidence for the involvement of influenza A (fowl plague Rostock) virus protein P2 in ApG and mRNA primed in vitro RNA synthesis. Journal of General Virology 57(Pt. 2): 407-13.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Eleven temperature-sensitive (ts) mutants of influenza A (fowl plague, Rostock) virus were analysed for in vitro RNA transcriptase activity in reactions primed by ApG or globin mRNA at 31 degrees C or at 40.5 degrees C, the restrictive temperature for ts mutant growth. Only those ts mutants studied which were defective in RNA segment 1, coding for the virion P2 protein, were defective in RNA transcriptase activity when compared to wild-type virus. Mutants having a defect in the P2 protein had no significant RNA transcriptase activity in reactions at 40.5 degrees C primed by globin mRNA. However, one mutant showed RNA transcriptase activity similar to wild-type virus at 40.5 degrees C when ApG (0.3 mM) was used as primer. The results suggest that influenza (fowl plague, Rostock) P2 protein is directly involved in the mRNA priming reaction, as well as in the RNA transcription reaction in vitro.

            Descriptors:  dinucleoside phosphates, influenza A virus avian metabolism, RNA nucleotidyltransferases metabolism, RNA replicase metabolism, RNA viral biosynthesis, viral proteins physiology, adenosine monophosphate analogs and derivatives, adenosine monophosphate physiology, globins, guanosine analogs and derivatives, guanosine physiology, influenza A virus avian genetics, mutation, RNA, messenger physiology, transcription, genetic.

Nicolau, C., H.D. Klenk, A. Reimann, K. Hildenbrand, and H. Bauer (1978). Molecular events during the interaction of envelopes of myxo- and RNA-tumor viruses with cell membranes. A 270 MHz H nuclear magnetic resonance study. Biochimica Et Biophysica Acta 511(1): 83-92.  ISSN: 0006-3002.

            NAL Call Number:  381 B522

            Descriptors:  cell membrane physiology, cell transformation, viral, influenza A virus avian, influenza A virus, Newcastle disease virus, sarcoma viruses, avian, cell membrane ultrastructure, chick embryo, fibroblasts physiology,  magnetic resonance spectroscopy.

Niemann, H., J. Dabrowski, U. Dabrowski, R. Geyer, W. Keil, H.D. Klenk, and S. Stirm (1985). The major oligosaccharides in the large subunit of the hemagglutinin from fowl plague virus, strain Dutch. Structure elucidation by one-dimensional and two-dimensional 1H nuclear magnetic resonance and by methylation analysis. European Journal of Biochemistry FEBS 146(3): 523-32.  ISSN: 0014-2956.

            NAL Call Number:  QP501.E8

            Abstract:  The N-glycosidically linked glycans in the large subunit (HA1) of the hemagglutinin from fowl plague virus, strain Dutch (containing about 15%, w/w, of carbohydrates), were liberated by alkaline hydrolysis, and were filtrated through Bio-Gel as the re-N-acetylated oligosaccharide alditols. One major fraction (90%, mol/mol) was obtained. It was subfractionated by concanavalin A affinity chromatography and was analyzed by methylation/capillary gas chromatography/mass fragmentography and especially by one-dimensional and two-dimensional 1H nuclear magnetic resonance. The major HA1 glycans, which are not sialylated, were thus found to comprise about 40%, 30% and 20% (mol/mol), respectively, of biantennary intersected, biantennary, and triantennary N-acetyllactosaminic ('complex') oligosaccharides. About two thirds of the internal GlcNAc residues in these glycans are substituted by Fuc(alpha 1----6), all the triantennary species carry the third Gal(beta 1----4)GlcNAc(beta 1----unit at the Man(alpha 1----6)-branch, and roughly one fourth of the N-acetyllactosamine units in the non-intersected biantennary oligosaccharides are incomplete.

            Descriptors:  hemagglutinins viral, influenza A virus avian analysis, oligosaccharides analysis, amino acids analysis, chemistry, hemagglutination tests, hemagglutinin glycoproteins, influenza virus, hexosamines analysis, magnetic resonance spectroscopy methods, mass fragmentography, methylation, polysaccharides analysis.

O'Neill, R.E., R. Jaskunas, G. Blobel, P. Palese, and J. Moroianu (1995). Nuclear import of influenza virus RNA can be mediated by viral nucleoprotein and transport factors required for protein import. Journal of Biological Chemistry 270(39): 22701-4.  ISSN: 0021-9258.

            NAL Call Number:  381 J824

            Abstract:  We have fluorescently labeled one of the eight genomic segments of influenza virus RNA and a recombinant influenza viral protein, the nucleoprotein (NP), to investigate the requirement for their uptake into nuclei of digitonin-permeabilized cells. We found that the influenza viral NP behaves like a nuclear localization sequence (NLS) containing protein. Thus, at 0 degrees C it docks at the nuclear envelope only in the presence of the heterodimeric karyopherin (either karyopherin alpha 1 beta or karyopherin alpha 2 beta), and docking is competitively inhibited by an unlabeled NLS containing substrate. Like other NLS-containing proteins, at 20 degrees C NP is imported into the nucleus after further addition of the GTPase Ran and of p10. In contrast, the fluorescently labeled, 890-nucleotide-long viral RNA segment does not dock to the nuclear envelope or enter the nucleus either in the presence of exogenous cytosol or of karyopherin heterodimer, Ran, and p10. However, in the presence of NP the RNA is able to dock and enter the nucleus with transport requirements indistinguishable from those for docking and entry of NP. These data indicate that uptake of the influenza virus RNA segment is not via a signal in the RNA but via an NLS of a viral protein such as NP.

            Descriptors:  cell nucleus metabolism, influenza A virus avian physiology, nuclear proteins metabolism, RNA viral metabolism, binding, competitive, cell nucleus virology, digitonin, kinetics, liver virology, macromolecular systems, nuclear envelope metabolism, rats, rats, inbred buf.

Obrosova Serova, N.P., N.L. Pushkarskaia, S.V. Lavrov, and A.I. Kuznetsov (1976). Deistvie proizvodnykh adamantana na reproduktsiiu virusa grippa A v kul'ture tkani i na zhivotnykh [Effect of adamantan derivatives on reproduction of influenza A virus in tissue culture and in animals]. Voprosy Virusologii (6): 689-92.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  amantadine analogs and derivatives, antiviral agents, influenza prevention and control, influenza A virus avian drug effects, amantadine pharmacology, amantadine therapeutic use, mice, virus replication drug effects.

Ogawa, T. and M. Ueda (1981). Genes involved in the virulence of an avian influenza virus. Virology 113(1): 304-13.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, influenza A virus genetics, brain, chick embryo, chickens, electrophoresis, genotype, influenza A virus growth and development, influenza A virus pathogenicity, RNA viral genetics, recombination, genetic.

Ohuchi, M., A. Cramer, M. Vey, R. Ohuchi, W. Garten, and H.D. Klenk (1994). Rescue of vector-expressed fowl plague virus hemagglutinin in biologically active form by acidotropic agents and coexpressed M2 protein. Journal of Virology 68(2): 920-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The hemagglutinin of the Rostock strain of fowl plague virus was expressed in CV-1 cells by a simian virus 40 vector, and its stability in the exocytotic transport process was examined by a fusion assay. A 50-fold increase in the fusion activity of the hemagglutinin was observed when expression occurred in the presence of ammonium chloride, Tris-HCl, or high doses of amantadine. When chloroquine, another acidotropic agent, was used, the hemagglutinin exposed at the cell surface had to be activated by trypsin, because intracellular cleavage was inhibited by this compound. Hemagglutinin mutants resistant to intracellular cleavage did not require acidotropic agents for full expression of fusion activity, when treated with trypsin after arrival at the cell surface. These results indicate that fowl plague virus hemagglutinin expressed by a simian virus 40 vector is denatured in the acidic milieu of the exocytotic pathway and that cleavage is a major factor responsible for the pH instability. Coexpression with the M2 protein also markedly enhanced the fusion activity of the hemagglutinin, and this effect was inhibited by low doses of amantadine. These results support the concept that M2, known to have ion channel function, protects the hemagglutinin from denaturation by raising the pH in the exocytotic transport system. The data also stress the importance of acidotropic agents or coexpressed M2 for the structural and functional integrity of vector-expressed hemagglutinin.

            Descriptors:  hemagglutinins viral biosynthesis, influenza A virus avian metabolism, viral matrix proteins pharmacology, ammonium chloride pharmacology, base sequence, biological transport, cell fusion drug effects, cultured cells, Cercopithecus aethiops, fluorescent antibody technique, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, hemagglutinins viral isolation and purification, hydrogen-ion concentration, influenza A virus avian genetics, membrane proteins biosynthesis, molecular sequence data, recombinant proteins biosynthesis, simian virus 40 genetics, viral fusion proteins biosynthesis, viral fusion proteins genetics, viral matrix proteins biosynthesis, viral matrix proteins genetics.

Ohuchi, M., A. Feldmann, R. Ohuchi, and H.D. Klenk (1995). Neuraminidase is essential for fowl plague virus hemagglutinin to show hemagglutinating activity. Virology 212(1): 77-83.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  When hemagglutinin (HA) of fowl plague virus (FPV) was expressed in CV-1 cells by a simian virus 40 vector, hemadsorption was barely detectable, although HA was exposed at the cell surface. However, treatment of HA-expressing cells with Vibrio cholerae neuraminidase (VCNA) resulted in extensive hemadsorption. VCNA treatment enhanced the electrophoretic mobility of the HA1 subunit of HA, indicating the removal of sialic acid. When two oligosaccharides in the vicinity of the receptor binding site of FPV HA were deleted by site-specific mutagenesis, VCNA treatment was not required for hemadsorption. Mutants which retained one of these oligosaccharides and mutants in which oligosaccharides not adjacent to the receptor binding site were deleted needed VCNA treatment to show hemadsorption. VCNA treatment also enhanced hemadsorption of vector-expressed HA of the WSN strain, which had a complex-type oligosaccharide in the vicinity of the receptor binding site, but had no effect on hemadsorption of Hong Kong type HA, which has a high-mannose type oligosaccharide adjacent to the receptor binding site. These results indicate that sialic acid on oligosaccharides near the receptor binding site interferes with hemadsorption. Thus, the neuraminidase is essential for FPV HA to show hemagglutinating activity.

            Descriptors:  hemagglutination, hemagglutinins viral metabolism, influenza A virus avian immunology, neuraminidase pharmacology, glucosaminidase, glycosylation, hemagglutinins viral chemistry, N-acetylneuraminic acid, sialic acids chemistry.

Ohuchi, M., C. Fischer, R. Ohuchi, A. Herwig, and H.D. Klenk (1998). Elongation of the cytoplasmic tail interferes with the fusion activity of influenza virus hemagglutinin. Journal of Virology 72(5): 3554-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The hemagglutinin (HA) of fowl plague virus was lengthened and shortened by site-specific mutagenesis at the cytoplasmic tail, and the effects of these modifications on HA functions were analyzed after expression from a simian virus 40 vector. Elongation of the tail by the addition of one to six histidine (His) residues did not interfere with intracellular transport, glycosylation, proteolytic cleavage, acylation, cell surface expression, and hemadsorption. However, the ability to induce syncytia at a low pH decreased dramatically depending on the number of His residues added. Partial fusion (hemifusion), assayed by fluorescence transfer from octadecylrhodamine-labeled erythrocyte membranes, was also reduced, but even with the mutant carrying six His residues, significant transfer was observed. However, when the formation of fusion pores was examined with hydrophilic fluorescent calcein, transfer from erythrocytes to HA-expressing cells was not observed with the mutant carrying six histidine residues. The addition of different amino acids to the cytoplasmic tail of HA caused an inhibitory effect similar to that caused by the addition of His. On the other hand, a mutant lacking the cytoplasmic tail was still able to fuse at a reduced level. These results demonstrate that elongation of the cytoplasmic tail interferes with the formation and enlargement of fusion pores. Thus, the length of the cytoplasmic tail plays a critical role in the fusion process.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, histidine metabolism, influenza A virus avian metabolism, membrane fusion physiology, amino acids, biological transport, cell line, cell membrane metabolism, Cercopithecus aethiops, cytoplasm metabolism, hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus genetics, histidine genetics, influenza A virus avian genetics, intracellular fluid, mutagenesis.

Ohuchi, M., R. Ohuchi, A. Feldmann, and H.D. Klenk (1997). Regulation of receptor binding affinity of influenza virus hemagglutinin by its carbohydrate moiety. Journal of Virology 71(11): 8377-84.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The hemagglutinin (HA) of the fowl plague virus (FPV) strain of influenza A virus has two N-linked oligosaccharides attached to Asn123 and Asn149 in the vicinity of the receptor binding site. The effect of these carbohydrate side chains on the binding of HA to neuraminic acid-containing receptors has been analyzed. When the oligosaccharides were deleted by site-specific mutagenesis, HA expressed from a simian virus 40 vector showed enhanced hemadsorbing activity. Binding was so strong under these conditions that erythrocytes were no longer released by viral neuraminidase and that release was significantly reduced when neuraminidase from Vibrio cholerae was used. Similarly, when these oligosaccharides were removed selectively from purified viruses by N-glycosidase F, such virions were unable to elute from receptors, although they retained neuraminidase activity. Thus, release of FPV from cell receptors depends on the presence of the HA glycans at Asn123 and Asn149. On the other hand, receptor binding was abolished when these oligosaccharides were sialylated after expression in the absence of neuraminidase (M. Ohuchi, A. Feldmann, R. Ohuchi, and H.-D. Klenk, Virology 212:77-83, 1995). These observations indicate that the receptor affinity of FPV HA is controlled by oligosaccharides adjacent to the receptor binding site.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, influenza A virus avian metabolism, neuraminidase chemistry, receptors, virus metabolism, binding sites, cell line, cultured cells, dogs, erythrocytes virology, glycosylation, hemagglutinin glycoproteins, influenza virus metabolism, neuraminidase metabolism, structure activity relationship, virion metabolism.

Ohuchi, M., M. Orlich, R. Ohuchi, B.E. Simpson, W. Garten, H.D. Klenk, and R. Rott (1989). Mutations at the cleavage site of the hemagglutinin after the pathogenicity of influenza virus A/chick/Penn/83 (H5N2). Virology 168(2): 274-80.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Six variants that form plaques in chick embryo cells in the absence of trypsin have been isolated from the apathogenic avian influenza virus A/chick/Pennsylvania/1/83 (H5N2). Unlike the wild-type, the plaque variants contain a hemagglutinin that is cleaved in chick embryo cells and MDCK cells. The variants differ also from the wild-type in their pathogenicity for chickens. Nucleotide sequence and oligosaccharide analysis of the hemagglutinin have revealed that, unlike natural isolates with increased pathogenicity (Y. Kawaoka et al., 1984, Virology 139, 303-316; Y. Kawaoka and R. G. Webster, 1985, Virology 146, 130-137), the variants obtained in vitro have retained an oligosaccharide at asparagine 11 that is believed to interfere with the cleavage site of the wild-type. However, all variants showed mutations in the hemagglutinin resulting in an increased number of basic groups at the cleavage site. These observations demonstrate that masking of the cleavage site by an oligosaccharide is overcome by an enhancement of the basic charge at the cleavage site.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian pathogenicity, amino acid sequence, base sequence, cultured cells, chick embryo, chickens, fowl plague microbiology, genes viral, hemagglutinins viral analysis, influenza A virus avian genetics, influenza A virus avian growth and development, molecular sequence data, mutation, oligosaccharides analysis, plaque assay, trypsin pharmacology.

Ohuchi, R., M. Ohuchi, W. Garten, and H.D. Klenk (1991). Human influenza virus hemagglutinin with high sensitivity to proteolytic activation. Journal of Virology 65(7): 3530-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To examine the prerequisites for cleavage activation of the hemagglutinin of human influenza viruses, a cDNA clone obtained from strain A/Port Chalmers/1/73 (serotype H3) was subjected to site-directed mutagenesis and expressed in CV-1 cells by using a simian virus 40 vector. The number of basic residues at the cleavage site, which consists of a single arginine with wild-type hemagglutinin, was increased by inserting two, three, or four additional arginines. Like wild-type hemagglutinin, mutants with up to three additional arginines were not cleaved in CV-1 cells, but insertion of four arginines resulted in activation. When the oligosaccharide at asparagine 22 of the HA1 subunit of the hemagglutinin was removed by site-directed mutagenesis of the respective glycosylation site, only three inserted arginines were required to obtain cleavage. Mutants containing a series of four basic residues were also generated by substituting arginine for uncharged amino acids immediately preceding the cleavage site. The observation that these mutants were not cleaved, even when the carbohydrate at asparagine 22 of HA1 was absent, underscores the fact that the basic peptide had to be generated by insertion to obtain cleavage. The data show that the hemagglutinin of a human influenza virus can acquire high cleavability, a property known to be an important determinant for the pathogenicity of avian influenza viruses. Factors important for cleavability are the number of basic residues at the cleavage site, the oligosaccharide at asparagine 22, and the length of the carboxy terminus of HA1.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus human metabolism, amino acid sequence, arginine chemistry, base sequence, cloning, molecular, DNA mutational analysis, endopeptidases metabolism, glycoproteins metabolism, hemagglutinins viral chemistry, hemagglutinins viral genetics, molecular sequence data, oligonucleotides chemistry, protein processing, post translational, structure activity relationship.

Okazaki, K., Y. Kawaoka, and R.G. Webster (1989). Evolutionary pathways of the PA genes of influenza A viruses. Virology 172(2): 601-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Nucleotide sequences of the PA genes of influenza A viruses, isolated from a variety of host species, were analyzed to determine the evolutionary pathways of these genes and the host specificity of the genes. Results of maximum parsimony analysis of the nucleotide sequences indicate at least five lineages for the PA genes. Those from human strains represent a single lineage, whereas the avian genes appear to have evolved as two lineages--one comprising genes from many kinds of birds (e.g., chickens, turkeys, shorebirds, and ducks) and the other comprising only genes from gulls. H3N2 swine influenza virus PA genes are closely related to the currently circulating duck virus PA gene. By contrast, the H1N1 swine and equine virus PA genes appear to have evolved along independent lineages. Comparison of predicted amino acid sequences disclosed 10 amino acid substitutions in the PA proteins of all avian and H3N2 swine viruses that distinguished them from human viruses. The H1N1 swine viruses seem to be chimeras between human and avian viruses and they contain 8 amino acids not shared by other viruses. The equine viruses also appear to show their own amino acid substitutions. These findings indicate that the PA genes of influenza A viruses have evolved in different pathways defined by apparently unique amino acid substitutions and host specificities. They also indicate that influenza A viruses have been transmitted from avian to mammalian species.

            Descriptors:  genes viral, influenza A virus genetics, RNA replicase, RNA viral genetics, viral proteins genetics, amino acid sequence, base sequence, birds, cloning, molecular, ducks, evolution, horses, influenza A virus avian genetics, influenza A virus human genetics, influenza A virus, porcine genetics,  molecular sequence data, poultry, sequence homology, nucleic acid, species specificity, swine.

Olofsson, S., U. Kumlin, K. Dimock, and N. Arnberg (2005). Avian influenza and sialic acid receptors: more than meets the eye? Lancet Infectious Diseases 5(3): 184-8.  ISSN: 1473-3099.

            Abstract:  Given our recent discoveries that the ocular human pathogens adenovirus serotype 37 and enterovirus serotype 70 use sialic acid linked to galactose via alpha2,3 glycosidic bonds as a cellular receptor, we propose that the presence of this receptor in the eye also explains the ocular tropism exhibited by zoonotic avian influenza A viruses such as subtype H5N1 in Hong Kong in 1997, H7N7 in the Netherlands in 2003, H7N2 in the USA in 2003, and H7N3 in Canada in 2004. We also draw attention to the implications this hypothesis may have for epizootic and zoonotic influenza, and the initiation of future pandemics.

            Descriptors:  Adenoviridae classification, eye diseases virology, avian influenza pathology, cell surface physiology receptors, zoonoses virology, Adenoviridae pathology, birds, avian influenza epidemiology, avian influenza transmission, serotyping, zoonoses transmission, sialic acid.

Orlich, M., D. Khatchikian, A. Teigler, and R. Rott (1990). Structural variation occurring in the hemagglutinin of influenza virus A/turkey/Oregon/71 during adaptation to different cell types. Virology 176(2): 531-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The influenza virus A/turkey/Oregon/71 (H7N3) has been adapted to grow in MDCK or chicken embryo cells (CEC) in the absence of trypsin. Changes occurred in the biological properties of the virus variants selected, depending on the cell type used for adaptation. They coincided with enhanced hemagglutinin (HA) activation by intracellular proteolytic cleavage. In the case of MDCK cell selected variants growth, plaque formation, and HA cleavability were restricted to this cell type, whereas the CEC-derived variants displayed altered activities in a broad range of host cells. Unlike the wild-type virus and its MDCK cell-derived variants, CEC variants had acquired pathogenic properties for chickens. By nucleotide sequence analysis of the HA genes of the MDCK cell variants several point mutations were found, which were localized predominantly at the distal, globular part of the HA molecule. The mechanism by which these point mutations increased HA cleavability has not been defined. In the CEC-derived variants besides point mutations, an insertion of 54 nucleotides adjacent to the cleavage site was observed, which corresponds in its sequence to a region in the 28 S ribosomal RNA. This insertion is probably responsible for the altered cleavability of the CEC variants' HA, leading to increased growth potential and pathogenicity.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, RNA viral genetics, adaptation, physiological, amino acid sequence, base sequence, cell line, DNA, viral genetics, electrophoresis, polyacrylamide gel, glycosylation, hemagglutinins viral metabolism, influenza A virus avian growth and development, influenza A virus avian metabolism, molecular sequence data, mutation, plaque assay.

Osidze, N.G. (1977). Attenuation of avian influenza virus A/fowl/SSSR/315/70. Sbornik Nauchnykh Trudov, Moskovskaya Veterinarnaya Akademiya 93: 60-61.

            Descriptors:  avian influenza virus, cell culture, attenuation, fowl.

Otsuki, K., Y. Kawaoka, T. Nakamura, and M. Tsubokura (1982). Pathogenicity for chickens of avian influenza viruses isolated from whistling swans and a black-tailed gull in Japan. Avian Diseases 26(2): 314-20.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  We isolated 24 Hav1 Neq1 and 18 Hav6 Nav3 influenza viruses from such free-living wild waterfowl as whistling swans, black-tailed gulls, and tufted ducks in western Japan in 1980. Two Hav1 Neq1 viruses isolated from a whistling swan and a black-tailed gull and a Hav6 Nav3 virus from a whistling swan were examined for their pathogenicity for chickens. Five-week-old specific-pathogen-free chickens were inoculated with the viruses intratracheally or intraperitoneally. Virus was recovered successfully from all the organs, including the brain, despite the absence of signs of disease. The intracerebral pathogenicity index scores obtained for the Hav1 Neq1 viruses were 0.43 and 0.87; the score for the Hav6 Nav3 virus was 0.43. No virus produced plaques in cultivated chick embryo fibroblast cells in the absence of trypsin.

            Descriptors:  animal population groups microbiology, animals, wild microbiology, birds microbiology, chickens microbiology, ducks microbiology, influenza A virus avian pathogenicity, chick embryo, Japan, specific pathogen free organisms, terminology.

Ozaki, H., E.A. Govorkova, C. Li, X. Xiong, R.G. Webster, and R.J. Webby (2004). Generation of high-yielding influenza A viruses in African green monkey kidney (Vero) cells by reverse genetics. Journal of Virology 78(4): 1851-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. Recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategies to produce influenza vaccine. Although cell-based systems are being developed, barriers remain that need to be overcome if the potential of these systems is to be fully realized. These barriers include, but are not limited to, potentially poor reproducibility of viral rescue with reverse genetics systems and poor growth kinetics and yields. In this study we present a modified A/Puerto Rico/8/34 (PR8) influenza virus master strain that has improved viral rescue and growth properties in the African green monkey kidney cell line, Vero. The improved properties were mediated by the substitution of the PR8 NS gene for that of a Vero-adapted reassortant virus. The Vero growth kinetics of viruses with H1N1, H3N2, H6N1, and H9N2 hemagglutinin and neuraminidase combinations rescued on the new master strain were significantly enhanced in comparison to those of viruses with the same combinations rescued on the standard PR8 master strain. These improvements pave the way for the reproducible generation of high-yielding human and animal influenza vaccines by reverse genetics methods. Such a means of production has particular relevance to epidemic and pandemic use.

            Descriptors:  influenza A virus avian growth and development, influenza A virus human growth and development, influenza vaccine, reassortant viruses growth and development, vero cells virology, Cercopithecus aethiops, influenza A virus avian genetics, influenza A virus human genetics, reassortant viruses genetics, viral nonstructural proteins genetics, virus cultivation, virus replication.

Padilla, N.R., F.E. Aburto, C.M. Fraire, and N.L. Padilla (2004). Influenza aviar: histopatologia y deteccion viral por rt-pcr en tejidos fijados con formalina e incluidos en parafina. [Avian influenza: histopathology and viral detection in formalin-fixed, paraffin-embedded tissues by RT-PCR]. Veterinaria Mexico 35(1): 1-19.  ISSN: 0301-5092.

            NAL Call Number:  SF604.V485

            Descriptors:  infection, acute renal tubular necrosis, avian influenza, non suppurative encephalitis, vasculitis, reverse transcription polymerase chain reaction, clinical techniques, diagnostic techniques, viral replication, chickens.

Paffenholz, V. and C. Scholtissek (1973). Mode of replication and temperature characteristics of the RNA polymerase of an influenza virus in vitro. Zeitschrift Fur Naturforschung. Teil C Biochemie, Biophysik, Biologie, Virologie 28(3): 208-13.  ISSN: 0341-0471.

            NAL Call Number:  QH301.Z4

            Descriptors:  influenza A virus avian enzymology, DNA directed RNA polymerases biosynthesis, temperature, templates, genetic, virulence.

Pagnini, P., A. Bonaduce, F. Martone, and M. Compagnucci (1969). Profilassi della pseudo-peste aviaria. Ricerche con vaccino inattivato in adiuvante oleoso. [Prevention of avian pseudo-plague. Research with inactivated vaccine in oily adjuvant]. Acta Medica Veterinaria 15(5): 267-311.  ISSN: 0001-6136.

            NAL Call Number:  41.8 AC84

            Descriptors:  fowl plague prevention and control, viral vaccines, influenza A virus avian, vaccination.

Pancheva, S. (1983). Efekt na antibiotika A 23187 vurkhu reproduktsiia na niakoi virusi v kletuchni kulturi. [Effect of antibiotic A-23187 on the reproduction of viruses in cell cultures]. Acta Microbiologica Bulgarica 13: 29-32.  ISSN: 0204-8809.

            NAL Call Number:  QR1.A37

            Descriptors:  calcimycin pharmacology, virus replication drug effects, viruses drug effects, chick embryo, dose response relationship, drug, herpesvirus 1, suid drug effects, influenza A virus avian drug effects, Newcastle disease virus drug effects, vaccinia virus drug effects, virus cultivation, viruses growth and development.

Park, C.H., K. Matsuda, Y. Sunden, A. Ninomiya, A. Takada, H. Ito, T. Kimura, K. Ochiai, H. Kida, and T. Umemura (2003). Persistence of viral RNA segments in the central nervous system of mice after recovery from acute influenza A virus infection. Veterinary Microbiology 97(3-4): 259-68.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  One-hundred thirty-seven BALB/c mice were intranasally inoculated with neurotropic avian influenza A virus (H5N3). Thirty-nine of these mice died within 16 days post-inoculation (PID) and 98 of the mice recovered from the infection. To investigate whether viral antigens and genomes persist in the central nervous system (CNS) of recovered mice, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods were performed. Histopathologically, mild interstitial pneumonia and non-suppurative encephalomyelitis restricted to the basal part of the frontal lobe of the cerebrum, brain stem and thoracic spinal cord were observed in BALB/c mice until 40 PID. Small amounts of viral antigens were detected in the brain and spinal cord and some viral RNA segments (NA, NP, M, PA, HA, NS, PB1) were intermittently detected in the CNS until 48 PID. Immunosuppression of these mice by dexamethazone (DEX) treatment did not increase the frequency of detection of the lesions, viral antigens or genomes. These findings suggest that viral genomes of neurovirulent influenza virus persist with restricted transcriptive activity in the CNS of the mice even after clinical recovery from the infection.

            Descriptors:  central nervous system virology, fowl plague virology, influenza A virus avian isolation and purification, RNA viral analysis, brain pathology, brain virology, central nervous system pathology, disease models, animal, fowl plague mortality, fowl plague pathology, immunohistochemistry veterinary, influenza A virus avian genetics, mice, mice inbred BALB c, random allocation, reverse transcriptase polymerase chain reaction veterinary, specific pathogen free organisms.

Penn, C. (1989). The role of RNA segment 1 in an in vitro host restriction occurring in an avian influenza virus mutant. Virus Research 12(4): 349-59.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  A temperature sensitive mutant, ts C47, derived from A/FPV/Rostock/34 and with a ts mutation in RNA segment 8, fails to form plaques in MDCK cells. From data obtained with reassortant viruses using the human influenza isolate A/FM/1/47 it was apparent that more than one mutation contributed to the temperature-sensitive (ts) and host range (hr) phenotypes of ts C47, and the phenotype of reassortants containing RNA segment 1 from A/FM/1/47 indicated that this segment was involved. A single nucleotide substitution at nucleotide 1961, resulting in valine instead of methionine in the predicted amino acid sequence of polypeptide PB2, was found in RNA segment 1 of ts C47, but this mutation did not segregate with the attenuated phenotype on gene reassortment. The following conclusions are drawn: (a) that ts C47 has at least two mutations in addition to that already known to exist in RNA segment 8, one of which (that in RNA segment 1) does not contribute to the observed ts hr phenotypes and (b) that the hr phenotype can be suppressed by substitution of RNA segment 1 by that of another strain.

            Descriptors:  influenza A virus avian genetics, RNA viral physiology, amino acid sequence, base sequence, cultured cells, chick embryo, dogs, influenza A virus avian growth and development, influenza A virus human genetics, kidney, phenotype, plaque assay, RNA viral genetics, recombination, genetic, temperature.

Penn, C.R., D. Blaas, E. Kuechler, and B.W. Mahy (1982). Identification of the cap-binding protein of two strains of influenza A/FPV. Journal of General Virology 62(Pt. 1): 177-80.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  We have identified the cap-recognizing protein of two strains of influenza A fowl plague virus (FPV) by photoaffinity labelling of virion proteins with a photoreactive analogue of the 5'-methyl cap structure of messenger RNA. The cap-recognizing protein of influenza A/FPV/Rostock/34 is the P2 polypeptide, and that of influenza A/FPV/Dutch/27 (Dobson) is the P3 polypeptide. In each case the cap-recognizing protein is the product of RNA segment 1.

            Descriptors:  carrier proteins analysis, influenza A virus avian analysis, viral proteins analysis, affinity labels, carrier proteins genetics, influenza A virus avian genetics, RNA cap binding proteins, RNA viral genetics, viral proteins genetics.

Perdue, M.L. (1992). Naturally occurring NS gene variants in an avian influenza virus isolate. Virus Research 23(3): 223-40.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The A/Turkey/Wisconsin/68 (H5N9) isolate of avian influenza (AI) consists of two virus populations which have different NS genes and differ in their biological responses in chicken embryos. They were classified as being either rapidly embryo-lethal (REL) or slowly embryo-lethal (SEL), (Avian Dis., 33 (1989) 695-706). In this study, sequence analysis identified only two nucleotide differences between the two NS genes, creating single amino acid differences in both the NS1 and the NS2 protein. The difference in the NS1 protein appears to be neutral, while the differences in the NS2 places a phenylalanine at position 48. This amino acid has not been previously demonstrated at this position in an NS2 sequence and its presence results in a distinct hydrophobic shift in the region. The sequence specifying the phenylalanine also creates an EcoRI site in the cDNA of the REL NS gene. Analysis of several clones showed that this site appears to co-segregate with the REL characteristic. Molecular differences between the two NS gene variants were reflected by differences in the kinetics of early protein synthesis in infected cells. In particular, the NS2 protein is in higher concentration (relative to the NS1) in SEL-infected cells than in REL-infected cells. No differences were detectable, however, in the rates of viral replication, either in cell culture or in embryos. Also, the REL or SEL rate was established early during infection of the embryo and could not be competed out by the other variant population 3 h after inoculation. Thus, these two natural NS gene variants appear to specify early differences which influence the time of death of an infected embryo but the differences do not appear to influence virus replication.

            Descriptors:  capsid genetics, influenza A virus avian genetics, viral core proteins genetics, amino acid sequence, base sequence, capsid metabolism, chick embryo, cloning, molecular, DNA restriction enzymes, embryo, nonmammalian microbiology, gene expression regulation, viral, genetic vectors, influenza A virus avian classification, influenza A virus avian pathogenicity, molecular sequence data,  polymerase chain reaction, RNA viral isolation and purification, sequence homology, nucleic acid, variation genetics genetics, viral core proteins metabolism, viral nonstructural proteins, virus replication.

Perdue, M.L., M. Garcia, J. Beck, M. Brugh, and D.E. Swayne (1996). An Arg-Lys insertion at the hemagglutinin cleavage site of an H5N2 avian influenza isolate. Virus Genes 12(1): 77-84.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  Recent isolations of H5N2 subtype avian influenza (AI) viruses in North America have raised questions concerning their origin, transmission to commercial poultry, and potential for virulence. One ratite-origin isolate of low pathogenicity, A/emu/TX/39924/93 (H5N2), was subjected to a procedure that rapidly selects and/or amplifies highly pathogenic (HP) strains. The resulting highly virulent derivative had an altered hemagglutinin (HA) gene containing an additional six nucleotides at position 970-975 in the HA1 coding region. This resulted in an arg-lys insertion near the proteolytic cleavage site of the HA protein. The remainder of the HA sequence differed by an additional seven amino acids from the parent. The HA precursor of the derivative, but not the parent, was readily cleaved during replication in cell culture without addition of trypsin. In experimentally infected chickens, the derivative produced lesions typical of highly pathogenic avian influenza. A reverse transcriptase-polymerase chain reaction (RT-PCR) primer set was designed to amplify exclusively from molecules with the inserted six nucleotides. The set yielded product only from the selected derivative samples and not the parent. Thus, the levels of the HP variants in the parent stock were undetectable, or the insertion occurred rapidly during the selection process.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, arginine, base sequence, chickens, fowl plague genetics, fowl plague virology, lysine, molecular sequence data, mutation, phylogeny, polymerase chain reaction, RNA viral genetics.

Perdue, M.L., M. Garcia, J. Crawford, and J. Latimer (1996). Heterogeneity in the hemagglutinin protein among the H5N2 avian influenza isolates from central Mexico. Proceedings of the Western Poultry Diseases Conference 45: 8-13.

            NAL Call Number:  SF995.W4

            Descriptors:  avian influenza virus, Mexico, America, influenza virus, Latin America, North America, orthomyxoviridae, viruses.

Perdue, M.L., M. Garcia, D. Senne, and M. Fraire (1997). Virulence-associated sequence duplication at the hemagglutinin cleavage site of avian influenza viruses. Virus Research 49(2): 173-86.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Recent highly pathogenic (HP) field isolates of avian influenza (AI) virus from Mexico all possess an insertion of at least two basic amino acids (arg-lys) at the cleavage site of the hemagglutinin (HA) glycoprotein. One HP isolate has additional information which yields a 4 amino acid insert (arg-lys-arg-lys). We present here the nucleotide sequence of the HA gene of this unique isolate and compare it to recent H5N2 and other avian influenza isolates. The complete HA nucleotide sequence of the isolate and phylogenetic relationship suggest that it was derived in direct succession from a non-pathogenic strain isolated about 1 month earlier. The unique insertion sequence is a direct duplication of part of the purine-rich region preceding the arginine codon at the HA cleavage site. This evidence along with other data in this report provide compelling support for a proposed model explaining the mechanism of spontaneous, virulence-related insertions in type A influenza viruses.

            Descriptors:  hemagglutinins chemistry, hemagglutinins genetics, influenza A virus avian genetics, influenza A virus avian pathogenicity, repetitive sequences, nucleic acid, amino acid sequence, base sequence, chick embryo, chickens, endopeptidases, fowl plague virology, hydrolysis, influenza A virus avian chemistry, models, molecular, molecular sequence data, nucleic acid conformation, protein structure, secondary, sequence alignment, structure activity relationship, virulence.

Perdue, M.L., J. Latimer, C. Greene, and P. Holt (1994). Consistent occurrence of hemagglutinin variants among avian influenza virus isolates of the H7 subtype. Virus Research 34(1): 15-29.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Several field isolates of avian influenza virus of the H7 subtype were analyzed for the presence of hemagglutinin variants by labeling proteins in cells infected with virus clones, and reacting with monoclonal antibodies. Each strain was shown to contain two distinct electrophoretic variants of the uncleaved hemagglutinin. In the A/Tk/Ore/71 (H7N3) isolate, two variants remained in the population through 35 laboratory passages, indicating both are stable and may be important to expression of the viral phenotype. Nucleotide sequence analysis of the HA gene of these two variants demonstrated differences at several amino acid positions in the HA1 subunit including one glycosylation site. Three additional recent North American isolates were also each found to contain two electrophoretic variants occurring within populations as few as one embryo passage away from the original clinical specimen. Pulse-chase assays indicated none of the variant HA molecules were cleavable in chick embryo fibroblasts. In the highly pathogenic Australian isolate; A/Ck/Victoria/75, both HA variants are cleavable in fibroblasts, without added trypsin, and the differences are localized within the HA1 region. With all the strains tested, the slower migrating HA variant was associated with a consistently higher hemagglutinin titer in embryos. Finally, recent H7 isolates from imported birds (A/Soft Bill/Ill/92) also exhibit similar variants, indicating their occurrence is not limited to domestic poultry. This consistent presence of two distinct electrophoretic variants in several avian H7 isolates suggests multiple allelic forms of the H7 hemagglutinin.

            Descriptors:  antigenic variation genetics, hemagglutinins viral genetics, influenza A virus avian genetics, antibodies, monoclonal immunology, antibodies, viral immunology, chick embryo, chickens virology, electrophoresis, polyacrylamide gel, genes, structural, viral, glycosylation, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, influenza A virus avian classification, influenza A virus avian immunology, mice, mice inbred BALB c, protein processing, post translational, RNA viral genetics, sequence analysis, RNA.

Perdue, M.L., J.W. Latimer, and J.M. Crawford (1995). A novel carbohydrate addition site on the hemagglutinin protein of a highly pathogenic H7 subtype avian influenza virus. Virology 213(1): 276-281.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The highly pathogenic (HP) avian influenza isolate, A/Fowl/Victoria/76 (H7N7), contains two naturally occurring hemagglutinin (HA) variants. The two hemagglutinin proteins differ only in the possession of a potential asparagine-linked glycosylation site at amino acid position 188-190, which is near the proposed receptor binding region of the HA. Expanded virus plaques which possess the addition site exhibit more slowly migrating HA, subunits and are significantly more lethal in chickens than those which lack the site. When artificial mixtures of the two variants were inoculated in birds, as few as 1 in 1000 particles containing the glycosylation site was sufficient to exhibit 100% lethality in birds. The data raise the possibility that presence of carbohydrate near the receptor site on the H7 avian influenza virus hemagglutinin may influence virulence.

            Descriptors:  chickens, avian influenza virus, agglutinins, chemical composition, pathogenicity, mortality, biological properties, birds, domestic animals, domesticated birds, Galliformes, influenza virus, livestock, microbial properties, orthomyxoviridae, poultry, proteins, useful animals, viruses, glycosylation site, GENBANK z47199, molecular sequence data,  viral hemagglutinins, binding site, amino acid sequences, virulence.

Perdue, M.L. and D.L. Suarez (2000). Structural features of the avian influenza virus hemagglutinin that influence virulence. Veterinary Microbiology 74(1-2): 77-86.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  Analysis of the structure of the avian influenza (AI) virus hemagglutinin (HA) gene and protein has yielded a wealth of information on the virulence mechanisms of influenza viruses. The AI hemagglutinin appears to be unique in its capacity to accept basic amino acids at its proteolytic cleavage site (PCS). The association of multiple basic (MB) amino acids, HA cleavage, tissue spread and virulence by AI strains first proposed in the late 1970s and early 1980s [Klenk, H.D., Rott, R., Orlich, M., 1977. J. Gen. Virol. 36, 151-161; Bosch, F.X., Garten, W., Klenk, H.D., Rott, R., 1981. Virology 113, 725-735] has held fast for two decades now. While other structural characteristics and other genes can certainly influence virulence, the presence of MB amino acids at the PCS has provided a hallmark structural feature which justifies continuing sequence analysis of emerging field isolates of AI strains. In addition to this structural feature, the distal tip of the HA is prone to appearance and disappearance of glycosylation sites, some of which have been associated with virulence.The recent outbreaks of highly pathogenic AI in Mexico, Australia, Pakistan, Hong Kong and in the ongoing outbreak of moderately pathogenic H7 avian influenza in the northeast US have all provided new and useful information regarding the role of HA RNA and protein structure in both virulence and host adaptation. We have previously noted that stable RNA secondary structure near the PCS is related to the acquisition of virulence and have proposed that the secondary structure may promote the insertion of basic amino acids. In this report we evaluate the phylogenetic relationships for three recent isolates of highly pathogenic avian influenza viruses and the possible virulence factors associated with their primary and secondary structure.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, influenza A virus avian pathogenicity, glycosylation, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian classification, numerical analysis, computer assisted, peptide library, phylogeny, protein structure, secondary, structure activity relationship.

Perdue, M.L., P. Wainright, S. Palmieri, and M. Brugh (1989). In ovo competition between distinct virus populations in an avian influenza isolate. Avian Diseases 33(4): 695-706.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Embryo lethality patterns induced by an avian influenza virus isolate (A/Tk/Ws/68/H5N9) suggested that it contained more than one genetic form. Two different virus populations were recovered from the isolate by plaque isolation and limit-dilution cloning and were characterized with respect to their biological and molecular properties. They were very closely related but exhibited strikingly different mean death times (MDT) in 10-day-old chick embryos. One was rapidly embryo lethal (REL), while the other was slowly embryo lethal (SEL). The REL isolate demonstrated a small but measurable mortality rate in 4-week-old chicks, as did the parental isolate. The SEL isolate, however, was nonlethal to 4-week-old chicks. The embryo MDT induced by the parental isolate revealed a biphasic death pattern reflecting expression of both REL and SEL populations. Mixing experiments, using different amounts of the two cloned populations, demonstrated that expression of their unique phenotypic property (either REL or SEL) was competitive. The number of early or late embryo deaths was directly related to the input levels of each respective virus. The only molecular difference thus far detected between the two populations is in the nonstructural (NS) gene, with the REL clone possessing a faster migrating electrophoretic form of that RNA than the SEL clone. Both forms of the NS gene were present in the original parental isolate. This study thus demonstrates the competitive coexistence of two closely related virus populations within a single natural isolate.

            Descriptors:  orthomyxoviridae growth and development, RNA viral analysis, viral proteins analysis, chick embryo, clone cells, influenza etiology, influenza mortality, influenza veterinary, orthomyxoviridae isolation and purification, orthomyxoviridae pathogenicity, phenotype, plaque assay, virulence.

Perdue, M.L., P.O. Wainright, and M. Brugh (1990). Effects of chicken embryo age on time to death following infection by avian influenza viruses: implications for distinguishing highly pathogenic isolates. Virus Research 16(2): 137-52.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  When white leghorn (WL) chick embryos ranging in age from 8 to 13 days were inoculated with a variety of avian influenza virus (AIV) isolates, strain-specific differences in embryo mean death times (MDT) were observed. Non-highly pathogenic (nHP) strains killed 8 or 9 day-old embryos much more rapidly than 12 or 13 day-old embryos. Highly pathogenic (HP) strains, however, were less sensitive to embryo age resulting in similar MDTs in both older and younger embryos. These observations were consistent over a broad range of virus doses for both HP and nHP strains. When a HP derivative of H5N2 AIV was compared to its nHP parent, the derivative killed older embryos more rapidly than the parent virus, while MDTs in younger embryos were the same for both parent and derivative. The two strains further exhibited clear differences in the structure of their respective hemagglutinin, a previously described pathogenicity determinant for this virus. Thus it may be possible to readily demonstrate the HP phenotype in AIV strains based on MDT measurements in WL embryos.

            Descriptors:  chick embryo microbiology, orthomyxoviridae pathogenicity, orthomyxoviridae infections veterinary, poultry diseases mortality, antibodies, monoclonal immunology, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, orthomyxoviridae infections mortality, specific pathogen free organisms, time factors, viral envelope proteins immunology.

Pereira, H.G., A. Rinaldi, and L. Nardelli (1967). Antigenic variation among avian influenza A viruses. Bulletin of the World Health Organization 37(4): 553-8.  ISSN: 0042-9686.

            NAL Call Number:  449.9 W892B

            Descriptors:  orthomyxoviridae classification, antigens, complement fixation tests, Italy, poultry, serotyping.

Petri, T. and N.J. Dimmock (1981). Phosphorylation of influenza virus nucleoprotein in vivo. Journal of General Virology 57(Pt. 1): 185-90.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Two-dimensional analysis of polypeptides from A/FPV/Rostock/34 (FP/R)-infected chick embryos fibroblast cells using non-equilibrium pH gradient gel electrophoresis followed by polyacrylamide gel electrophoresis, showed that nucleoprotein (NP) was the only detectable virus phosphoprotein and was present in both the nucleus and cytoplasm. The kinetics of accumulation of phosphorylated NP in the nucleus and cytoplasm were similar, suggesting that the presence or absence of phosphate groups did not control the entry of NP into the nucleus. In the course of this study, two-dimensional analysis of [35S]methionine-labelled FP/R-infected cells revealed some major differences from previously published work which are discussed.

            Descriptors:  cell nucleus metabolism, cytoplasm metabolism, influenza A virus avian metabolism, nucleoproteins metabolism, viral proteins metabolism, cultured cells, chick embryo, fibroblasts, nucleoproteins analysis, phosphoproteins analysis, phosphoproteins metabolism, phosphorylation, viral proteins analysis.

Petri, T., S. Patterson, and N.J. Dimmock (1982). Polymorphism of the NS1 proteins of type A influenza virus. Journal of General Virology 61(Pt. 2): 217-31.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The type-specific non-structural protein 1 (NS1) of influenza A viruses was found to be heterogeneous with respect to charge, varying in pI by more than two orders of magnitude, and to phosphorylation. Phosphorylation was strain-specific, variable in extent between strains, and in some strains NS1 proteins were not detectably phosphorylated. Phosphorylation was not responsible for the major variations in charge as, paradoxically, the most acidic NS1 proteins were not phosphorylated. Cytoplasmic inclusions, which are formed between NS1 proteins and cellular RNA in infections with a number of human strains, were absent from A/FP/Rostock-infected cells and do not, therefore, appear to be essential in virus multiplication. We suggest that the acidic nature of the NS1 of A/FP/Rostock may prevent it from binding RNA and hence from forming inclusions. The variation in charge of NS1 proteins which we determined experimentally correlates with the overall differences in charge adduced from published amino acid sequence and implications of this variability to the biological role of NS1 are discussed.

            Descriptors:  influenza A virus avian analysis, influenza A virus human analysis, influenza A virus analysis, viral proteins analysis, cell line, chick embryo, dogs, electrophoresis, polyacrylamide gel, inclusion bodies, viral analysis, influenza A virus growth and development, isoelectric point, phosphoproteins analysis, phosphorylation, species specificity, viral matrix proteins, viral nonstructural proteins, viral proteins metabolism.

Petrov, N.A., L.V. Mamaev, and S.I.A. Golovin (1988). Pervichnaia struktura gena belka PB2 virusa grippa A/FPV Veibridzh. [Primary structure of the gene encoding the PB2 protein in influenza virus A/FPB Weybridge]. Bioorganicheskaia Khimiia 14(4): 548-50.  ISSN: 0132-3423.

            NAL Call Number:  QD415.A1S62

            Abstract:  The complete nucleotide sequence of the cloned full-length DNA copy of the avian influenza virus A/FPV Weybridge PB2 gene has been determined.

            Descriptors:  genes viral, influenza A virus avian genetics, viral proteins genetics, amino acid sequence, base sequence, molecular sequence data.

Philpott, M., B.C. Easterday, and V.S. Hinshaw ( 1989). Neutralizing epitopes of the H5 hemagglutinin from a virulent avian influenza virus and their relationship to pathogenicity. Journal of Virology 63(8): 3453-8.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To define and characterize the major neutralizing epitopes of the H5 hemagglutinin, a panel of monoclonal antibodies specific for the H5 hemagglutinin of the virulent avian influenza virus A/Turkey/Ontario/7732/66 (H5N9) was prepared. Antibodies which neutralized infectivity of the virus were used to select a panel of escape mutants. Reactivity patterns of the panel of monoclonal antibodies against the panel of mutants by both enzyme-linked immunosorbent assay serology and hemagglutination inhibition operationally defined five distinct epitopes on the H5 molecule. The mutants were analyzed in vivo for virulence in chickens, and the findings indicate that viruses with mutations in four of five epitopes were no less virulent than the wild type, producing a rapidly fatal disease, while all viruses with mutations in the fifth epitope (group 1 mutants) were attenuated. These group 1 mutants were unaltered in the cleavage properties of the hemagglutinin, suggesting that the mechanism of attenuation is unrelated to processing of the hemagglutinin. One of the group 1 mutants, 77B1v, was characterized for its ability to produce necrosis of the spleen and was found to produce none of the lesions in the spleen which are characteristic of the wild-type virus, although virus was present in this organ. The results suggest an altered tissue tropism, perhaps sparing a population of cells critical to an effective immune response.

            Descriptors:  epitopes analysis, hemagglutinins viral immunology, influenza A virus avian immunology, antibody specificity, chickens, cross reactions, enzyme linked immunosorbent assay, epitopes genetics, epitopes immunology, fowl plague microbiology, hemagglutination inhibition tests, hemagglutination tests, influenza A virus avian genetics, influenza A virus avian pathogenicity, mutation, neutralization tests, virulence.

Philpott, M., C. Hioe, M. Sheerar, and V.S. Hinshaw (1990). Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus. Journal of Virology 64(6):  2941-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The H5 hemagglutinin (HA) of a highly virulent avian influenza virus, A/Turkey Ontario/7732/66 (H5N9), was previously shown to have five neutralizing epitopes, and escape mutants within one epitope (group 1) were markedly attenuated (M. Philpott, B. C. Easterday, and V. S. Hinshaw, J. Virol. 63:3453-3458, 1989). To define the genetic changes related to these antigenic and biologic properties, the HA genes of mutants within each of the epitope groups were sequenced by using the polymerase chain reaction. The mutations in the attenuated group 1 mutants were located near the distal tip of the HA molecule in close proximity to the receptor-binding site, on the basis of alignment with the three-dimensional structure of the H3 HA. All group 1 mutations involved charged amino acids. The group 1 mutants, similar to the wild-type virus, spread systemically and were recovered from the spleens of infected chickens but, unlike the wild-type virus, failed to produce severe necrosis in the spleens. Viral replication in the spleens was investigated by in situ hybridization of spleen sections from chickens infected with the wild-type or attenuated mutants. Wild-type virus replication was demonstrated in large, mononuclear, macrophagelike cells; however, group 1 mutant virus was detected attached only to erythrocytes within the red pulp. These results suggest that the attenuated mutants differ in their cell tropism within the spleen.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, mutation, amino acid sequence, base sequence, chick embryo, chickens, cloning, molecular, DNA, viral genetics, influenza A virus avian pathogenicity, influenza A virus avian physiology, molecular sequence data, spleen microbiology, virulence genetics, virus replication.

Philpott, M.S., B.C. Easterday, and V.S. Hinshaw (1989). Antigenic and phenotypic variants of a virulent avian influenza virus selected during replication in ducks. Journal of Wildlife Diseases 25(4): 507-13.  ISSN: 0090-3558.

            NAL Call Number:  41.9 W64B

            Abstract:  To evaluate the replication of a highly virulent avian influenza A virus in a potential reservoir host, mallard ducks (Anas platyrhynchos) were inoculated with the virulent strain A/Ty/Ont/7732/66 (H5N9). Viruses recovered from the ducks were analyzed by hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) and found to possess antigenically altered viral hemagglutinins. Plaque formation on the Madin-Darby Canine Kidney (MDCK) cell line and on primary chicken embryo cells was investigated, and isolates recovered from the ducks differed from the wild type by being unable to form plaques on MDCK cells without trypsin. This phenotype did not appear to be due to inefficient cleavage of the hemagglutinin by host cell proteases since hemagglutinin immunoprecipitated from cell lysates was cleaved. Although the plaquing phenotype suggested attenuation of the isolates from the ducks, they were not significantly altered in their virulence for chickens shown by infectivity studies in vivo. These results indicate that replication of influenza A/Ty/Ont/7732/66 virus in ducks can produce antigenic and phenotypic variants which are still highly virulent for domestic poultry.

            Descriptors:  ducks microbiology, fowl plague microbiology, influenza A virus avian pathogenicity, antibodies, monoclonal immunology, antigenic variation, cell line, chickens, enzyme linked immunosorbent assay, fowl plague mortality, hemagglutination inhibition tests, hemagglutinins viral analysis, hemagglutinins viral metabolism, influenza A virus avian growth and development, influenza A virus avian immunology, influenza A virus avian physiology, phenotype, plaque assay, virulence, virus replication.

Pint, L.H. and R.A. Lamb (2004). Viral ion channels as models for ion transport and targets for antiviral drug action. FEBS Letters 560(1-3): 1-2.  ISSN: 0014-5793.

            NAL Call Number:  QD415.F4

            Descriptors:  influenza infection, solid state NMR, laboratory techniques, antiviral drug action targets, immune system, membranes, immune surveillance, ion transport models, proton transfer reaction model, viral life cycle.

Podcherniaeva, R.I.A., V.K. Blinova, N.D. L'vov, N.L. Pusharskaia, and G.A. Galegov (1980). Peredacha rezistentnosti k remantadinu v rezul'tate posledovatel'-nykh rekombinatsii virusov grippa cheloveka i zhivotnykh. [Transmission of remantadine resistance as a result of successive recombinations of human and animal influenza viruses]. Voprosy Virusologii (6): 705-8.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  adamantane analogs and derivatives, influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic drug effects, rimantadine antagonists and inhibitors, antigens, viral genetics, chick embryo, drug resistance, microbial, influenza A virus avian drug effects, influenza A virus human drug effects, microbial sensitivity tests, rabbits.

Podcherniaeva, R.I.A., V.K. Blinova, M.V. Ronina, E.I. Sklianskaia, and N.V. Kaverin (1980). Antigennye rekombinanty virusov grippa cheloveka s virusami, vydelennymi ot dikikh ptits. [Antigenic recombinants of human influenza viruses with viruses isolated from wild birds]. Voprosy Virusologii (4): 419-24.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Antigenic recombinants obtained by crossing of different human and animal influenza viruses were studied for some genetic markers and specific proteins in the resulting recombinants were analyses. In a number of cases the origin of inner virion proteins (NP and M) from one or the other parent and nonstructural NS proteins was established.

            Descriptors:  antigens, viral genetics, birds microbiology, influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic, antigens, viral analysis, genetic markers, species specificity, viral proteins genetics.

Podcherniaeva, R.I.A., I.A. Miasnikova, V.K. Blinova, R.V. Belousova, and V.P. Andreev (1979). Izuchenie svoistv virusov grippa, vydelennykh v 1976 g. ot chaikovykh ptits v Astrakhanskoi oblasti. [Properties of the influenza viruses isolated in 1976 from gulls in Astrakhan Province]. Voprosy Virusologii (3): 227-32.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Investigation of a number of properties of influenza viruses isolated from Laridae birds in the Astrakhan region showed that in one epizootic focus avian influenza viruses with different hemagglutinins and identical neuraminidase may circulate among Laridae birds. Among viruses with the antigenic formula Hav5Nav2 clear-cut differences in virulence and plaque-forming capacity were demonstrated.

            Descriptors:  birds microbiology, influenza A virus isolation and purification, antigens, viral analysis, chick embryo, chickens, cytopathogenic effect, viral, hemagglutination, viral, hemagglutinins viral analysis, influenza A virus immunology, influenza A virus pathogenicity, mice, neuraminidase analysis, plaque assay, Russia, virulence, virus replication.

Podcherniaeva, R.I.A., M.I. Sokolov, V.K. Blinova, A.G. Uzunova, and S.V. Lavrov (1972). Izuchenie mezhvidovoi rekombinatsii virusov grippa AO i istinnoi chumy ptits. [Interspecies recombination of influenza AO and fowl plague viruses]. Voprosy Virusologii 17(5): 559-64.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  influenza A virus avian, orthomyxoviridae drug effects, recombination, genetic, amantadine pharmacology, drug resistance, microbial.

Podchernyaeva, R.J., R.G. Webster, V.V. Skovorodka, A.I. Klimov, and V.M. Zhdanov (1989). Molecular and biological properties of a variant of avian influenza A/Seal/Massachusetts/1/80 (H7N7) virus that is pathogenic for mice. Acta Virologica 33(1): 38-42.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  A/Seal/Mass/80 influenza virus has been shown to be closely related antigenically and genetically to avian influenza H7N7 viruses, however, the virus does not replicate efficiently in avian species but does replicate in most mammals, except mice (Hinshaw et al., Infect. Immun., 34, 351-361, 1981). In order to develop a model defining the molecular changes that occur during acquisition of virulence, the A/Seal/Mass/80 virus was adapted to growth in mouse lungs. The adaptation was accompanied by changes in a number of properties of the haemagglutinin as well as by changes in other genes of the virus as determined by RNA: RNA hybridization.

            Descriptors:  influenza A virus pathogenicity, genes viral, hemagglutinins viral, influenza A virus genetics, lethal dose 50, lung microbiology, mice, neutralization tests, nucleic acid hybridization, RNA viral analysis, serial passage, variation genetics, virulence.

Podchernyaeva, R.Y.A., V.K. Blinova, N.N. Sokolova, V.R. Farashyan, V.M. Zhdanov, S.D. Irzhanov, D.K. Lvov, and Y.u.Z. Ghendon (1983). Comparative studies on biological properties and genome composition of influenza virus recombinants. Acta Virologica 27(3): 209-16.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Some biological properties and the genome composition of antigenic recombinants obtained by crossing of human and animal influenza viruses were studied. Analysis of the recombinants has shown that upon heating of virions in vitro thermostability of the haemagglutinin (HA) does not necessarily correlate with the properties of parent HA; apparently it depended not only on the properties of the HA itself, but also on the peculiarities of other virion proteins. All recombinants obtained by crossing of pathogenic and apathogenic for mice parents either had a reduced pathogenicity for mice or were apathogenic. In some instances, reduction or loss of pathogenicity was observed in recombinants which inherited only one gene from the apathogenic parent; however, the data obtained suggest that pathogenicity involves functions of a number of genes. Human and animal influenza virus strains under study proved to be capable of replication in human embryo tracheal and kidney organ cultures. The degree of reproduction of the recombinants was either lower or higher as compared to the parent strains.

            Descriptors:  genes viral, influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic, chick embryo, hemagglutinins viral immunology, influenza A virus avian immunology, influenza A virus avian physiology, influenza A virus human immunology, influenza A virus human physiology, organ culture, virus replication.

Podchernyaeva, R.Y.A., L. Dohner, R.M. Herrmann, V.K. Blinova, and V.T. Ivanova (1982). Studies on some genetic properties of antigenic recombinants of influenza viruses. Acta Virologica 26(4): 227-33.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Two groups of antigenic recombinants Hav4N1 were obtained by recombination of human influenza virus H0N1 with two avian influenza viruses isolated from ducks in 1956 and terns in 1978 and possessing the same surface antigen Hav4 Nav1. Recombinants obtained by crossing A/PR/8/34 and A/duck/CSSR/56 viruses showed a lower ability to reproduce at optimal and lowered temperatures and differed in the thermosensitivity of haemagglutinin and neuraminidase. An analysis of virus-specific proteins of the recombinants revealed different combinations of genes coding for internal (Pl, NP) and nonstructural (NS1) proteins. Recombinants obtained by crossing A/PR/8/34 and A/tern/Frunze/334/78 viruses possessed a thermostable haemagglutinin; they produced plaques of a size characteristic of avian influenza but, as distinct from the latter, they were practically not eluted from fowl erythrocytes. Polypeptide analysis of these recombinants showed that the genes coding for NP, M and NS1 proteins were inherited from the A/tern/Frunze/334/78 strain.

            Descriptors:  antigens, viral genetics, influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic, antigens, viral analysis, hemagglutinins viral analysis, influenza A virus avian immunology, influenza A virus human immunology, neuraminidase immunology, viral proteins analysis.

Poon, L.L., E. Fodor, and G.G. Brownlee (2000). Polyuridylated mRNA synthesized by a recombinant influenza virus is defective in nuclear export. Journal of Virology 74(1): 418-27.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The poly(A) tail of influenza virus mRNA is synthesized by reiterative copying of a U track near the 5' end of the virion RNA (vRNA) template by the viral RNA polymerase. We have engineered a novel influenza A/WSN/33 virus which contains a neuraminidase (NA) vRNA with its U track mutated into an A track. Instead of synthesizing poly(A)-tailed NA mRNA, this novel virus synthesizes poly(U)-tailed NA mRNA. In infected cells, most poly(U)-tailed NA mRNA was retained in the nucleus, while most control polyadenylated NA mRNA was transported to the cytoplasm. These results suggest that the poly(A) tail is important for efficient nuclear export of NA mRNA. The mutant virus produced a reduced amount of NA and showed an attenuated phenotype, suggesting that poly(A) signal mutants of this type might be useful as potential live attenuated virus vaccines. In addition, this virus mutant might provide a useful model to further elucidate the basic mechanisms of mRNA nuclear export.

            Descriptors:  cell nucleus metabolism, influenza A virus avian genetics, poly U metabolism, RNA, messenger biosynthesis, recombination, genetic, base sequence, biological transport, chick embryo, DNA primers, mutation, neuraminidase genetics, nucleic acid conformation, RNA, messenger chemistry, RNA, messenger metabolism.

Porter, A.G., C. Barber, N.H. Carey, R.A. Hallewell, G. Threlfall, and J.S. Emtage (1979). Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA. Nature 282(5738): 471-7.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Abstract:  A synthetic fowl plague virus (FPV) haemagglutinin gene has been cloned in bacteria and the complete sequence of the RNA gene deduced. It is 1,742 nucleotides long and the mRNA codes for 56.3 amino acids in an uninterrupted sequence. The nature of some of the important domains in the haemagglutinin has been established, and their structure is discussed in relation to their function. Extensive amino acid sequence homologies exist between FPV and human influenza haemagglutinins.

            Descriptors:  genes, structural, genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, viral proteins genetics, amino acid sequence, codon, DNA repair, DNA, recombinant, RNA, messenger genetics.

Porter, A.G., J.C. Smith, and J.S. Emtage (1980). Nucleotide sequence of influenza virus RNA segment 8 indicates that coding regions for NS1 and NS2 proteins overlap. Proceedings of the National Academy of Sciences of the United States of America 77(9): 5074-8.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  The smallest RNA segment of influenza A viruses (vRNA segment 8) has recently been shown to code for two unrelated nonstructural proteins (NS1 and NS2) translated from separate mRNAs. Molecular weight considerations indicated that there might not be enough space on vRNA segment 8 for the two coding regions unless they overlap. We have recently cloned in bacterial plasmids several genes of an avian influenza A virus, fowl plague virus (EPV), and now present the complete nucleotide sequence of FPV RNA segment 8 largely determined from the cloned DNA. The DNA sequence predicts two open protein synthesis reading frames that can be translated into polypeptides of sizes similar to those of NS1 and NS2. The coding regions for these polypeptides overlap by the equivalent of 43-60 amino acids, the exact amount depending on which of several possible methionines initiates the synthesis of NS2.

            Descriptors:  genes, structural, genes viral, influenza A virus avian genetics, viral proteins genetics, amino acid sequence, base sequence, cloning, molecular, codon genetics, DNA restriction enzymes, genes, synthetic, molecular weight, plasmids, RNA viral genetics.

Portincasa, P., G. Conti, and C. Chezzi (1990). Abortive replication of influenza A viruses in HeLa 229 cells. Virus Research 18(1): 29-40.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Several experimental data support the idea that certain mammalian cells are unable to replicate influenza viruses type A, although these viruses can efficiently penetrate the cells. This cannot be attributed to a lack of specific receptors on the cell surface, but depends upon the failure of specific step(s) to occur during viral growth. Here we report a study of abortiveness of human and avian type A influenza viruses in HeLa 229 cells. Viral polypeptide synthesis was monitored by [35S]methionine pulse labelling at several time points after infection, showing that normal amounts of virus-induced components were synthesized. Cellular fractionation of HeLa 229 cells infected by influenza viruses showed that the distribution of viral proteins into nuclear and cytoplasmic compartments was comparable to that seen in the permissive host, chick embryo fibroblasts. Viral HA glycoprotein, produced during the infectious cycle, was entirely found in the cytoplasm of infected HeLa 229 cells. The polypeptide was able to agglutinate red blood cells but did not show positive haemadsorption even at late times of infection. Therefore it seems that during the maturation of viral particles there is a failure of the haemagglutinin to perform a correct insertion into the plasma membrane of infected HeLa 229 cells.

            Descriptors:  fibroblasts microbiology, hemagglutinins viral metabolism, influenza A virus avian growth and development, influenza A virus human growth and development, cell membrane metabolism, chick embryo, HeLa cells, hemadsorption, hemagglutinin glycoproteins, influenza virus, influenza A virus avian metabolism, influenza A virus human metabolism, methionine metabolism, virus replication.

Portincasa, P., G. Conti, and C. Chezzi (1991). Defective insertion of haemagglutinin as a cause of abortivity of influenza A viruses in HeLa 229 cells. Microbiologica 14(4): 351-5.  ISSN: 0391-5352.

            NAL Call Number:  QR1.M57

            Abstract:  A number of experimental data demonstrate that certain mammalian cells are unable to replicate Influenza viruses type A. In these cellular hosts the viruses can efficiently perform their biological as well as biochemical activities but the production of mature viral particles is greatly restricted. Here we report a study of abortiveness of human and avian type A Influenza viruses in HeLa 229 cells in which the final stages of maturation of viral particles seem to be affected. We show that the incorrect insertion of virus-coded haemagglutinin into the plasma membrane might be the cause of the unpermissive condition of infection exhibited by this cellular host.

            Descriptors:  hemagglutinins viral metabolism, influenza A virus avian physiology, influenza A virus human physiology, virus replication, cultured cells, chick embryo, HeLa cells, hemadsorption.

Portnoy, J. and T.C. Merigan (1971). The effect of interferon and interferon inducers on avian influenza. Journal of Infectious Diseases 124(6): 545-52.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  fluorenes therapeutic use, influenza drug therapy, influenza A virus avian drug effects, interferons therapeutic use, polynucleotides therapeutic use, polysaccharides therapeutic use, cultured cells drug effects, chick embryo, chickens, disease models, animal, ethylamines therapeutic use,  injections, intravenous, interferons biosynthesis, interferons blood, poly I C pharmacology, poly I C therapeutic use, polysaccharides pharmacology, temperature, virus replication drug effects.

Possee, R.D., G.C. Schild, and N.J. Dimmock (1982). Studies on the mechanism of neutralization of influenza virus by antibody: evidence that neutralizing antibody (anti-haemagglutinin) inactivates influenza virus in vivo by inhibiting virion transcriptase activity. Journal of General Virology 58(Pt. 2): 373-86.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Influenza viruses, which had lost up to 99.999% infectivity by incubation with antibody (a) specific for the haemagglutinin (HA) or with monoclonal alpha-HA, attached on to and penetrated chick embryo fibroblast (CEF) cells to the same extent as non-neutralized virus. Neutralized virus was also uncoated efficiently as shown by the accumulation of virion RNA in the nucleus and virion envelope in the cytoplasm. Polyacrylamide gel electrophoresis of virion RNA segments recovered from the nucleus or cytoplasm of cells inoculated with neutralized or non-neutralized virus showed that antibody did not potentiate degradation of RNA. However, these RNAs were not expressed since virus-induced proteins were not detected in cells to which neutralized virus had been added. Assay of virion transcriptase of neutralized virus in vitro showed that its activity was reduced up to sevenfold compared with non-neutralized virus, and annealing studies showed that no detectable transcription took place in vivo with neutralized virus. These studies support the conclusion that antibody directed specifically against the HA protein on the outer surface of the influenza virus particle neutralizes infectivity by inactivating virion transcriptase activity and it is suggested that antibody to HA brings about allosteric rearrangements in the HA molecule which are transmitted across the virus envelope to the interior of the particle.

            Descriptors:  antibodies, viral physiology, DNA directed RNA polymerases antagonists and inhibitors, hemagglutinins viral immunology, influenza A virus avian immunology, influenza A virus human immunology, cultured cells, chick embryo, influenza A virus avian enzymology, influenza A virus avian growth and development, influenza A virus human enzymology, influenza A virus human growth and development, neutralization tests, viral proteins biosynthesis.

Pravdina, N.F., T.V. Veselovskaia, N.L. Pushkarskaia, and G.Z. Galegov (1972). Nekotorye metodicheskie voprosy izucheniia belkovogo sostava miksovirusov metodom elektroforeza v poliakrilamidonom gele [Methodological problems of studying the protein composition of myxoviruses by the polyacrylamide gel electrophoresis method]. Voprosy Meditsinskoi Khimii 18(2): 158-61.  ISSN: 0042-8809.

            Descriptors:  electrophoresis, polyacrylamide gel methods, orthomyxoviridae analysis, paramyxoviridae analysis, viral proteins analysis, influenza A virus avian analysis, influenza A virus avian isolation and purification, molecular weight, Newcastle disease virus analysis, Newcastle disease virus isolation and purification, orthomyxoviridae isolation and purification, paramyxoviridae isolation and purification.

Pravdina, N.F., T.V. Veselovskaia, V.D. Smirnov, and G.A. Galegov (1985). Ingibiruiushchee deistvie dezoksiadenilil-(3'-5')-dezoksiguanozina na aktivnost' RNK-polimerazy virusa grippa A. [Inhibitory effect of deoxyadenylyl-(3'-5')-deoxyguanosine on the RNA-polymerase activity of influenza virus A]. Voprosy Meditsinskoi Khimii 31(5): 123-5.  ISSN: 0042-8809.

            Abstract:  Deoxyadenylylguanosine (dAdG, 0.2-0.4 mM), affecting the RNA polymerase activity, caused inhibition of transcription of the influenza A virus in presence of precursor AdG by 50-60% and a 80-85% inhibition in absence of the precursor. The inhibitor exhibited its effect independently on the time of addition into an incubation mixture. Addition of 0.5 mM inhibitor into a cultural medium inhibited reproduction of the influenza A virus in a culture of chicken embryonal fibroblasts.

            Descriptors:  DNA directed RNA polymerases antagonists and inhibitors, deoxyadenine nucleotides, deoxyguanosine, influenza A virus avian enzymology, oligodeoxyribonucleotides pharmacology, virus replication drug effects, cultured cells, chickens, influenza A virus avian physiology.

Prokudina, E.N., N.P. Semenova, V.M. Chumakov, and I.A. Rudneva (2004). Transient disulfide bonds formation in conformational maturation of influenza virus nucleocapsid protein (NP). Virus Research 99(2): 169-75.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  It has been previously shown that influenza virus nucleocapsid protein (NP) forms homooligomers in vivo. Our analyses revealed that the reducing agent dithiothreitol (DTT) introduced in pulse labeling period prevented further formation of native NP-oligomers. The shortly pulse-labeled non-reduced newly synthesized NP possessed a relatively faster mobility in non-reducing PAGE and a higher resistance to protease than the reduced one. These data suggest that there is an early disulfide-dependent step in NP maturation and that the newly synthesized NP possesses the intrachain disulfide bonds. In contrast to the newly synthesized NP, the non-reduced chased NP possessed the same mobility in non-reducing PAGE and the same sensitivity to protease as the reduced NP. DTT introduced in the chase period did not prevent NP-oligomers formation and did not destabilize already formed NP-oligomers. This suggests that the chased NP monomers and NP-oligomers do not contain intrachain nor interchain disulfide bonds. It was also shown that the non-reduced newly synthesized NP could not form NP-NP complexes in vitro, and acquired such ability only after reducing. The possibility is discussed that there are several stages in the maturation of NP: the initial formation of intrachain disulfide-linked NP and conversion into disulfide-free NP, which forms non-covalently stabilized NP-oligomers. Early intrachain disulfide bonds may be necessary for the prevention of early spontaneous NP-NP association.

            Descriptors:  avian influenza A virus chemistry, nucleoproteins chemistry, RNA binding proteins, viral core proteins chemistry, cell line, disulfides chemistry, dithiothreitol metabolism, dogs, electrophoresis, polyacrylamide gel, immunoblotting, avian influenza A virus growth and development, nucleoproteins isolation and purification, oxidation reduction, protein binding, protein conformation, viral core proteins isolation and purification.

Prokudina, E.N., N.P. Semenova, V.M. Chumakov, I.A. Rudneva, and S.S. Yamnikova (2001). Extracellular truncated influenza virus nucleoprotein. Virus Research 77(1): 43-9.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  In the culture medium of MDCK cells infected with influenza A/Duck/Ukraine/1/63(H3N8) virus two kinds of virus nucleoprotein (NP) are detected: full-length 56 kDa NP and truncated 53 kDa NP. However, in infected cells 53 kDa NP may be detected only at short pulse and after 10 min chase it becomes nondetectable. The extracellular truncated 53 kDa NP is detected in free RNP, and not in the virions. Both extracellular free 53 and 56 kDa NP in the virions are completely oligomerized. Several data argue against the possibility of extracellular 53 kDa NP formation being a result of extracellular 56 kDa NP proteolytic degradation. Thus, the accumulation of extracellular 53 kDa NP takes place only in the course of infection, and the amount of 53 kDa NP is not increased during prolonged storage of cell-free culture medium at +37 degrees C. Moreover, all extracellular 56 kDa NP of A/Duck/Ukraine/1/63 influenza virus is present in the oligomeric form, and the latter, in contrast to the mononeric form, is highly resistant to proteases. The possibility is discussed that in the course of A/Duck/Ukraine/1/63 (H3N8) influenza virus infection a fraction of the synthesized 56 kDa monomeric NP undergoes the proteolytic cleavage in the infected cells before oligomerization and forms the 53 kDa NP. This 53 kDa NP is then oligomerized, enters the RNP and is quickly secreted from the cells.

            Descriptors:  influenza A virus avian metabolism, nucleoproteins metabolism, viral core proteins metabolism, cell line, culture media, dogs, ducks, fowl plague virology, influenza A virus avian pathogenicity, nucleoproteins chemistry, viral core proteins chemistry.

Prokudina Kantorovich, E.N. and N.P. Semenova (1996). Intracellular oligomerization of influenza virus nucleoprotein. Virology 223(1): 51-6.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  It has previously been shown that the purified influenza virus nucleoprotein (NP) forms the oligomers in vitro in NP preparations obtained from virions (Wiley et al., 1977, Virology, 79, 446-448; Ruigrok and Baudin, 1995, J. Gen. Virol., 76, 1009-1014) and infected cells (Becht and Weiss, 1991, Behring Inst Mitt., Justus-Liebig Universitat, Giessen, 89, 1-11). We have shown in this report that boiling-sensitive NP oligomers (di- and trimers) are formed in vivo in the course of intracellular influenza virus replication. They are detected by PAGE about 10 min after monomeric 56-kDa NP molecules are synthesized. NP oligomers are formed by different strains of influenza virus in different cell lines. Some influenza virus strains are characterized by complete conversion of NP monomers into oligomers and others by only partial conversion. In the Triton X-114 phase partitioning system NP oligomers show more hydrophobicity than NP monomers. NP oligomers are detected in the sedimentable and soluble fractions of both cell lysate and extracellular medium. The possibility is discussed that oligomeric NP is a native and functionally significant form of influenza virus NP.

            Descriptors:  influenza A virus metabolism, nucleoproteins metabolism, viral core proteins metabolism, cell line, chick embryo, dogs, ducks, influenza A virus avian metabolism, influenza A virus human metabolism, swine.

Pruett, P.S. and G.M. Air (1998). Critical interactions in binding antibody NC41 to influenza N9 neuraminidase: amino acid contacts on the antibody heavy chain. Biochemistry 37(30): 10660-70.  ISSN: 0006-2960.

            NAL Call Number:  381 B523

            Abstract:  Antibody NC41 binds to the subtype N9 neuraminidase (NA) of influenza virus A/tern/Australia/ G70c/75 and inhibits its enzyme activity. To address the molecular mechanisms by which antibodies interact with neuraminidase and the requirements for successful escape from antibody inhibition, we made amino acid substitutions in heavy chain CDRs of NC41. Antibody proteins expressed as a single-chain Fv (scFv) fused with maltose-binding protein were assayed for binding to NA by ELISA. Association constants (Ka) for wild-type and mutant scFvs are as follows: wild type, 2 x 10(7) M-1; Asn31-->Gln, 2 x 10(7) M-1; Glu96-->Asp, 1 x 10(7) M-1; Asp97-->Lys, 6 x 10(6) M-1; and Asn98-->Gln, 8 x 10(6) M-1. The Ka for intact NC41 antibody was 4 x 10(8) M-1 in the same assay, reflecting increased stability compared to that of the scFv. Mutations in the scFv antibody had less of an effect on binding than mutations in their partners on the NA, and modeling studies suggest that interactions involving the mutant antibody side chains occur, even without taking increased flexibility into account. Asp97 forms a salt link with NA critical contact Lys434; of the four mutants, D97K shows the largest reduction in binding to NA. Mutant N98Q also shows reduced binding, most likely through the loss of interaction with NA residue Thr401. Substitution N31Q had no effect on Ka. NC41 residue Glu96 interacts with NA critical contact Ser368, yet E96D showed only a 2-fold reduction in binding to NA, apparently because the H bond can still form. Asp97 and Asn98 provide the most important interactions, but some binding is maintained when they are mutated, in contrast to their partners on the NA. The results are consistent with maturation of the immune response, when the protein epitope is fixed while variation in the antibody paratope allows increasing affinity. Influenza viruses may exploit this general mechanism since single amino acid changes in the epitope allow the virus to escape from the antibody.

            Descriptors:  amino acids metabolism, antibodies, monoclonal metabolism, binding sites, antibody, immunoglobulins, heavy chain metabolism, influenza A virus avian immunology, neuraminidase immunology, amino acid sequence, amino acid substitution genetics, amino acids genetics, amino acids immunology, antibodies, monoclonal biosynthesis, antibodies, monoclonal chemistry, base sequence,  fluorescence polarization, immunoglobulin fragments biosynthesis, immunoglobulin fragments chemistry, immunoglobulin fragments metabolism, immunoglobulin variable region biosynthesis, immunoglobulin variable region chemistry, immunoglobulin variable region metabolism, immunoglobulins, heavy chain chemistry, immunoglobulins, heavy chain genetics, models, molecular, molecular sequence data, mutagenesis, site directed, neuraminidase chemistry, neuraminidase metabolism.

Puertollano, R., F. Martin Belmonte, J. Millan, M.C. de Marco, J.P. Albar, L. Kremer, and M.A. Alonso (1999). The MAL proteolipid is necessary for normal apical transport and accurate sorting of the influenza virus hemagglutinin in Madin-Darby canine kidney cells. Journal of Cell Biology 145(1): 141-51.  ISSN: 0021-9525.

            NAL Call Number:  442.8 J828

            Abstract:  The MAL (MAL/VIP17) proteolipid is a nonglycosylated integral membrane protein expressed in a restricted pattern of cell types, including T lymphocytes, myelin-forming cells, and polarized epithelial cells. Transport of the influenza virus hemagglutinin (HA) to the apical surface of epithelial Madin-Darby canine kidney (MDCK) cells appears to be mediated by a pathway involving glycolipid- and cholesterol- enriched membranes (GEMs). In MDCK cells, MAL has been proposed previously as being an element of the protein machinery for the GEM-dependent apical transport pathway. Using an antisense oligonucleotide-based strategy and a newly generated monoclonal antibody to canine MAL, herein we have approached the effect of MAL depletion on HA transport in MDCK cells. We have found that MAL depletion diminishes the presence of HA in GEMs, reduces the rate of HA transport to the cell surface, inhibits the delivery of HA to the apical surface, and produces partial missorting of HA to the basolateral membrane. These effects were corrected by ectopic expression of MAL in MDCK cells whose endogenous MAL protein was depleted. Our results indicate that MAL is necessary for both normal apical transport and accurate sorting of HA.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, proteolipids physiology,  antibodies, monoclonal pharmacology, biological transport drug effects, cell polarity, detergents pharmacology, dogs, epithelial cells metabolism, kidney, membrane lipids metabolism, membrane proteins metabolism, oligonucleotides, antisense pharmacology, proteolipids antagonists and inhibitors, proteolipids genetics, proteolipids immunology, rats, rats, wistar, transfection.

Purchase, H.G. (1989). Practical application of nucleic acid techniques to avian disease problems. Avian Diseases 33(4): 609-14.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  A workshop in which 17 practicing scientists participated was intended to address primarily people who use or could use biotechnology in their work and was confined to five techniques. Endonuclease fingerprinting and mapping involved cleaving nucleic acid with a specific restriction enzyme and separating the nucleic acid fragments by electrophoresis. Field and vaccine isolates of Pasteurella multocida could be distinguished; Salmonella enteritidis could be divided into three groups; chlamydia could be grouped into seven groups; and vaccinia, quail pox, and fowl pox could be clearly distinguished. Preparation of nucleic acid probes involved producing large amounts of labeled oligonucleotides, usually of unknown sequence. Successful probes had been made for infectious bursal disease virus, avian influenza virus, Newcastle disease virus, and infectious bronchitis virus. In Southern, Northern, and dot blotting, either DNA or RNA fragments were placed on or transferred to a solid substrate and probed. The procedure was able to detect infectious bursal disease virus, infectious bronchitis virus, Mycoplasma gallisepticum, and Marek's disease virus. In situ hybridization involved applying a labeled probe to frozen or fixed sections or to intact cells. In Polymerase chain reaction, two primers, some distance apart, were annealed to a denatured target DNA. Repeated cycles of DNA synthesis with a thermostable polymerase, denaturing, and reannealing resulted in great amplification of a rare sequence. After 30 cycles, a rare gene sequence could be amplified more than 10(6) times. It was used successfully to detect minute quantities of influenza virus and infectious bursal disease virus, and the process was used to facilitate DNA sequencing of coccidiosis gene segments.

            Descriptors:  poultry diseases diagnosis, blotting, northern, blotting, Southern, DNA restriction enzymes genetics, nucleic acid hybridization, nucleic acid probes, peptide mapping, polymerase chain reaction.

Pushkarskaia, N.L., Z.h.A. Shakarian, S.C. Lavrov, and G.A. Galegov (1972). Kombinirovannoe deistvie amantadina i DL-etionina na reproduktsiiu virusa grippa v kul'ture tkani. [Combined effect of amantadine and DL-ethionine on the reproduction of influenza virus in tissue culture]. Voprosy Virusologii 17(3): 267-9.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  amantadine pharmacology, ethionine pharmacology, influenza A virus avian drug effects, antiviral agents pharmacology, chickens, fibroblasts, tissue culture, virus replication drug effects.

Qiao ChuanLing, Jiang YongPing, Yu KangZhen, Tian GuoBin, and Chen HuaLan (2004). Immune efficacy of a recombinant fowlpox virus co-expressing HA and NA genes of avian influenza virus in SPF chickens. Agricultural Sciences in China 3(9): 716-720.  ISSN: 1671-2927.

            NAL Call Number:  S417.C6Z462

            Descriptors:  antibodies, experimental infections, gene expression, immunity, potency, recombinant vaccines, vaccine development, viral hemagglutinins, avian influenza virus, fowl pox virus, chickens, poultry, fowl, mortality.

Qiao ChuanLing, Yu KangZhen, Deng GuoHua, Wang XiuRong, Meng QingWen, Tian GuoBin, and Tang XiuYing (2003). Cloning of NA gene of avian influenza virus A/Goose/Guangdong/3/96(H5N1) and construction of transfer vector of recombinant fowlpox virus. Chinese Journal of Veterinary Science 23(2): 111-114.  ISSN: 1005-4545.

            NAL Call Number:  SF604.C58

            Descriptors:  complementary DNA, DNA cloning, genes, nucleotide sequences, avian influenza virus, fowl pox virus, poultry, geese, China, Guangdong.

Ramalho Santos, J., S. Nir, N. Duzgunes, A.P. de Carvalho, and M.C. de Lima (1993). A common mechanism for influenza virus fusion activity and inactivation. Biochemistry 32(11): 2771-9.  ISSN: 0006-2960.

            NAL Call Number:  381 B523

            Abstract:  The fusion of influenza virus (A/PR/8/34 strain) with PC-12 cells was monitored by a fluorescence assay, and the results were analyzed with a mass-action model which could explain and predict the kinetics of fusion. The model accounted explicitly for the reduction in the fusion rate constant upon exposure of the virus to low pH, either for the virus alone in suspension or for the virus bound to the cells. When the pH was lowered without previous viral attachment to cells, an optimal fusion activity was detected at pH 5.2. When the virus was prebound to the cells, however, reduction of pH below 5.2 resulted in enhanced fusion activity at the initial stages. These results were explained by the fact that the rate constants of both fusion and inactivation increased severalfold at pH 4.5 or 4, compared to those at pH 5.2. At pH 5.2, lowering the temperature from 37 to 20 or 4 degrees C resulted in a decrease in the fusion rate constant by more than 30- or 1000-fold, respectively. Inactivation of the virus when preincubated in the absence of target membranes at pH 5 was found to be rapid and extensive at 37 degrees C, but was also detected at 0 degrees C. Our results indicate a strong correlation between fusion and inactivation rate constants, suggesting that the rate-limiting step in viral hemagglutinin (HA)-mediated fusion, that is, rearrangement of viral glycoproteins at the contact points with the target membrane, is similar to that involved in fusion inactivation.

            Descriptors:  influenza A virus avian physiology, chick embryo, hydrogen-ion concentration, kinetics, mathematics, membrane fusion, PC-12 cells, rats, temperature.

Ratner, L.S., D. Omirzhanov, G.N. Pershin, and N.S. Bogdanova (1971). Izuchenie antivirusnogo deistviia khlozameshchennykh benzokhinona i gidrokhinona. [Study of antiviral effect of chlorine-substituted benzoquinine and hydroquinine]. Farmakologiia i Toksikologiia 34(1): 80-3.  ISSN: 0014-8318.

            Descriptors:  antiviral agents therapeutic use, chlorides administration and dosage, DNA viruses drug effects, hydroquinones administration and dosage, quinones administration and dosage, RNA viruses drug effects, virus diseases prevention and control, aphthovirus drug effects, chick embryo, cytopathogenic effect, viral drug effects, depression, chemical, herpesviridae drug effects, hydroquinones therapeutic use, influenza A virus avian drug effects, mice, quinones therapeutic use, tissue culture, viruses pathogenicity.

Rees, P.J. and N.J. Dimmock (1982). Kinetics of synthesis of influenza virus ribonucleoprotein structures. Journal of General Virology 59(Pt. 2): 403-8.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The synthesis of influenza virus ribonucleoprotein structures (RNPs) in infected chick embryo cells was analysed by polyacrylamide gel electrophoresis (PAGE) in the presence of sodium deoxycholate which resolves the RNPs into five size classes. A relatively small proportion of total RNPs accumulated in the nucleus but free NP protein was found there in large amounts over the period 1.5 to 4 h post-infection. In contrast, by 4 h post-infection, all cytoplasmic NP was complexed into RNP structures. At early times, during at 15 min pulse of (35S]methionine, nearly all the newly synthesized NP was incorporated into RNPs but by 4 h the majority of pulse-labelled NP was present as free protein. However, the proportion of free NP: NP in RNPs remained constant over the 1.5 to 4 h post-infection period, indicating that there was a delay before the NP synthesized later in infection was assembled into RNP structures. Individual RNP size classes were predominantly cytoplasmic and accumulated at similar rates but were not produced in equimolar amounts. The rates of synthesis of individual RNPs were in general agreement with their rates of accumulation with the remarkable exception of RNP d (containing RNA 7, the matrix protein gene). This was synthesized nearly 10-fold faster but accumulated at the same rate as the other RNPs. Possibly RNP d is more rapidly degraded than the other RNPs.

            Descriptors:  bacterial proteins biosynthesis, influenza A virus avian metabolism, nucleoproteins biosynthesis, ribonucleoproteins biosynthesis, cell nucleus metabolism, cultured cells, chick embryo, cytoplasm metabolism, influenza A virus avian growth and development, kinetics.

Reid, A.H., T.G. Fanning, T.A. Janczewski, R.M. Lourens, and J.K. Taubenberger (2004). Novel origin of the 1918 pandemic influenza virus nucleoprotein gene. Journal of Virology 78(22): 12462-70.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The nucleoprotein (NP) gene of the 1918 pandemic influenza A virus has been amplified and sequenced from archival material. The NP gene is known to be involved in many aspects of viral function and to interact with host proteins, thereby playing a role in host specificity. The 1918 NP amino acid sequence differs at only six amino acids from avian consensus sequences, consistent with reassortment from an avian source shortly before 1918. However, the nucleotide sequence of the 1918 NP gene has more than 170 differences from avian strain consensus sequences, suggesting substantial evolutionary distance from known avian strain sequences. Both the gene and protein sequences of the 1918 NP fall within the mammalian clade upon phylogenetic analysis. The evolutionary distance of the 1918 NP sequences from avian and mammalian strain sequences is examined, using several different parameters. The results suggest that the 1918 strain did not retain the previously circulating human NP. Nor is it likely to have obtained its NP by reassortment with an avian strain similar to those now characterized. The results are consistent with the existence of a currently unknown host for influenza, with an NP similar to current avian strain NPs at the amino acid level but with many synonymous nucleotide differences, suggesting evolutionary isolation from the currently characterized avian influenza virus gene pool.

            Descriptors:  nucleoproteins genetics, RNA binding proteins genetics, viral core proteins genetics, amino acid sequence, base sequence, influenza epidemiology, molecular sequence data, nucleoproteins chemistry, orthomyxoviridae classification, phylogeny, RNA binding proteins chemistry, regression analysis, swine, time factors, viral core proteins chemistry.

Reina, J. (2002). Factores de virulencia y patogenicidad en las cepas gripales (virus influenza tipo A) aviares y humanas. [Factors affecting the virulence and pathogenicity of avian and human viral strains (influenza virus type A)]. Enfermedades Infecciosas y Microbiologia Clinica 20(7): 346-53.  ISSN: 0213-005X.

            Abstract:  Most studies performed in avian viral strains seem to indicate that virulence is a polygenic phenomenon. However, hemagglutinin and neuraminidase and the genes codifying these substances (genes 4 and 6) play an essential role in viral pathogenesis. Avian strains can be classified as avirulent or virulent according to the ability of hemagglutinin to be activated by endoproteases of the respiratory tract only or by proteases from other tissues. This ability is based on the progressive development of mutations that lead to the substitution of the normal amino acids at the point of hemagglutinin hydrolysis by the other basic amino acids that determine the amplification of the spectrum of hydrolysis and activation. Neuraminidase participates in the acquisition of virulence through its capacity to bind to plasminogen and by increasing the concentration of activating proteases. Adaptation to the host, through recognition of the cell receptor, is another factor determining the virulence and interspecies transmission of avian strains. From an epidemiological point of view, viral strains should be subtyped and the activating capacity of hemagglutinin should be determined to identify their degree of virulence.

            Descriptors:  influenza A virus avian pathogenicity, influenza A virus human pathogenicity, hemagglutinins, neuraminidase, peptide hydrolases, virulence.

Reinacher, M. (1974). Intracellular maturation of fowl plague virus in chicken-embryo cell monolayers. Naturwissenschaften 61(3): 135.  ISSN: 0028-1042.

            NAL Call Number:  474 N213

            Descriptors:  influenza A virus avian growth and development, cell membrane, chick embryo, microscopy, electron, virus cultivation.

Reinacher, M., J. Bonin, O. Narayan, and C. Scholtissek (1983). Pathogenesis of neurovirulent influenza A virus infection in mice. Route of entry of virus into brain determines infection of different populations of cells. Laboratory Investigation a Journal of Technical Methods and Pathology 49(6): 686-92.  ISSN: 0023-6837.

            NAL Call Number:  448.8 L11

            Abstract:  Coinfection of a cell culture with a human and avian influenza A virus had yielded a recombinant virus with high neurovirulence for mice. This study reports on the comparative pathogenesis of central nervous system infection in mice between the parental human and the recombinant virus using the immunohistologic peroxidase-antiperoxidase method and virus assay of tissue suspensions. The human virus replicated poorly in mice and did not replicate in the brain even after intracerebral inoculation. In contrast, the recombinant virus replicated to high titer in the lung and brain with resulting viremia after inoculation of young mice by the intracerebral, intraperitoneal, or intranasal routes. Different populations of cells in the brain became infected after inoculation by each of the three routes: choroid plexus, and ependymal and subependymal cells after intracerebral inoculation; cells in perivenous areas, neurons in the olfactory bulbs and trigeminal ganglia and nuclear groups in the brainstem and midbrain after intranasal inoculation. Intraperitoneal inoculation resulted almost exclusively in the perivenous spread of the virus. The intranasal inoculation suggested that virus entry into the brain both by spread along nerve cell processes from the nasal mucosa to the brain and trigeminal ganglia and subsequent perivenous spread after viremia developed following virus replication in the lung. To dissect these two mechanisms we inoculated neonatal mice that had acquired high levels of serum antibody by nursing from actively immunized mothers. Intraperitoneal inoculation of these mice failed to cause infection, whereas intranasal inoculation resulted in the same pattern of cellular spread through the olfactory and trigeminal pathways as noted previously. This proved that this recombinant influenza virus could invade the central nervous system after infection via a natural route of infection. This highly neuroinvasive agent provides one example of the extent of virulence which can be acquired by recombination of apathogenic influenza viruses and raises a note of caution for adequate control of those agents generated in the laboratory.

            Descriptors:  brain diseases microbiology, influenza microbiology, influenza A virus avian pathogenicity, influenza A virus human pathogenicity, antigens, viral analysis, birds, brain microbiology, brain pathology, brain diseases immunology, brain diseases pathology, immunization, influenza immunology, influenza pathology, influenza A virus avian genetics, influenza A virus avian immunology, influenza A virus human genetics, influenza A virus human immunology, lung microbiology, lung pathology, mice, plaque assay, recombination, genetic, virulence, virus replication.

Reinacher, M. and E. Weiss (1975). Electron microscopical study of initial and final stages of fowl plague virus-replication in chick embryo cells. Archives of Virology 49(2-3): 187-97.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Cellular uptake of fowl plague virus occurs 10-30 minutes after inoculation of chick embryo cells. The penetration of the virions is by pinocytosis (viropexis); fusion with the cellular membrane has not been observed. After pinocytosis the virions become gradually disintegrated. Budding of newly formed virions from the cellular membrane starts 3 hours post inoculation (p.i.) and reaches its maximum 8 hours p.i. At the same time budding takes place into electron microscopically empty and autophagic vacuoles. Eight hours p.i. about 3 per cent of the infected cells show budding of virions from the surface and into cytoplasmic vacuoles. Labelling of the cellular membrane with ruthenium red demonstrated that these cytoplasmic vacuoles are not simple cross-sections of invaginations of the cellular membrane. Cluster-like structures were found at 6 hours p.i. in the nuclei of infected cells; however, the suggestion that the clusters develop from nucleoli could not be confirmed.

            Descriptors:  influenza A virus avian ultrastructure, virus replication, cell membrane microbiology, cell membrane ultrastructure, chick embryo, influenza A virus avian growth and development, pinocytosis, time factors, tissue culture, vacuoles microbiology, vacuoles ultrastructure.

Reinhardt, J. and T. Wolff (2000). The influenza A virus M1 protein interacts with the cellular receptor of activated C kinase (RACK) 1 and can be phosphorylated by protein kinase C. Veterinary Microbiology 74(1-2): 87-100.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  The M1 protein of influenza A virus has multiple regulatory functions during the infectious cycle, which include mediation of nuclear export of viral ribonucleoproteins, inhibition of viral transcription and a crucial role in virus assembly and budding. The only known modification of the M1 protein is by phosphorylation through yet-to-be-identified kinases. We postulated that at least some of the M1 functions are exerted or regulated through interactions with cellular components. In a screen for such cellular mediators, the protein receptor of the activated C-kinase (RACK 1) was identified by its interaction with the viral M1 protein in the yeast two hybrid system. The physical M1-RACK 1 interaction was confirmed in glutathione-S-transferase-based coprecipitation assays for the diverged M1 proteins of avian, swine and human influenza A virus strains. This conservation suggests that the M1-RACK 1 interaction is of general importance during influenza A virus infections. RACK 1 has previously been identified to specifically bind the activated form of protein kinase C (PKC) and is assumed to anchor the kinase at membranes in the vicinity of its substrates. Since the M1 protein becomes phosphorylated during influenza virus infection, we examined if PKC could catalyze the phosphate transfer. We demonstrate that virion-derived and recombinant M1 protein can indeed be efficiently phosphorylated by purified PKC. Moreover, in cell extracts, we detected M1 phosphorylation activity that was strongly reduced in the presence of the PKC-specific inhibitor compound GF109203X. These data suggest that PKC is the main M1-phosphorylating activity in the cell. Since both, the M1 protein and PKC have been shown to interact with RACK 1, we suggest that the M1-RACK 1 interaction is involved in M1 phosphorylation.

            Descriptors:  ion channels metabolism, peptides metabolism, protein kinase c metabolism, viral matrix proteins metabolism, binding sites,  chick embryo, electrophoresis, polyacrylamide gel, enzyme inhibitors pharmacology, indoles pharmacology, influenza A virus avian,  influenza A virus human, influenza A virus, porcine, maleimides pharmacology, phosphorylation, recombinant proteins metabolism, serine metabolism, software, structure activity relationship, threonine metabolism.

Rimmelzwaan, G.F., T. Kuiken, A.G. van, T.M. Bestebroer, R.A.M. Fouchier, and A.D.M.E. Osterhaus (2003). A primate model to study the pathogenesis of influenza A (H5N1) virus infection. Avian Diseases 47(Special Issue): 931-933.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Cynomolgus macaques (Macaca fascicularis) infected with influenza virus A/HongKong/156/97 (H5N1) developed acute respiratory distress syndrome (ARDS) with fever. Reverse transcriptase/polymerase chain reaction (RT/PCR) and virus isolation showed that the respiratory tract is the major target of the virus. The main lesion observed upon necropsy, performed 4 or 7 days postinfection, was a necrotizing bronchointerstitial pneumonia, similar to that found in primary influenza pneumonia in human beings. By immunohistochemistry, influenza virus antigen proved to be limited to pulmonary tissue and tonsils. The data indicate that ARDS and multiple organ dysfunction syndrome (MODS), observed in both humans and monkeys infected with this virus, are caused by diffuse alveolar damage from virus replication in the lungs alone.

            Descriptors:  infection, acute respiratory distress syndrome (ARDS), respiratory system disease, avian influenza, infectious disease, respiratory system disease, viral disease, bronchointerstitial pneumonia, respiratory system disease, multiple organ dysfunction syndrome (MODS), disease miscellaneous, immunohistochemistry immunologic techniques, laboratory techniques, necropsy clinical techniques, reverse transcriptase polymerase chain reaction (RT PCR) genetic techniques, laboratory techniques, viral isolation laboratory techniques, influenza pathogenesis viral replication.

Robertson, J.S. (1979). 5' and 3' terminal nucleotide sequences of the RNA genome segments of influenza virus. Nucleic Acids Research 6(12): 3745-57.  ISSN: 0305-1048.

            NAL Call Number:  QD341.A2N8

            Abstract:  EXtensive nucleotide sequence analysis of the 5' and the 3' terminal of the RNA segments of the genome of fowl plague virus, an avian strain of influenza virus, confirms the presence of a common sequence at the 5' terminus of each segment and a common sequence at the 3' terminus of each segment. Between the ends of each individual segment there is a complementary sequence which may be important in the control of transcription and replication of the genome. In addition, the probable sites of initiation of translation of fowl plague virus mRNA are indicated along with the corresponding NH2-terminal amino acid sequences of the virus polypeptides.

            Descriptors:  influenza A virus avian analysis, RNA viral analysis, base sequence, electrophoresis, polyacrylamide gel, genes viral.

Robertson, J.S. (1980). Nucleotide sequences from the terminal regions of fowl plague virus genome RNA. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 288(1029): 371-4.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Descriptors:  influenza A virus, RNA viral genetics, base sequence.

Robertson, J.S., E. Robertson, I. Roditi, J.W. Almond, and S.C. Inglis (1983). Sequence analysis of fowl plague virus mutant ts47 reveals a nonsense mutation in the NS1 gene. Virology 126(1): 391-4.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  A mutant of fowl plague virus, ts47, induces the synthesis in infected cells of a truncated NS1 polypeptide at both permissive and restrictive temperatures. Nucleotide sequence analysis of the segment coding for the NS1 polypeptide, segment 8, indicates that this aberration is due to a nonsense mutation. This mutation occurs in the region of the NS1 gene which overlaps with the NS2 gene and there is a corresponding amino acid substitution in the NS2 polypeptide. While it is not clear which polypeptide is responsible for the thermal instability of ts47, the loss of the COOH-terminal 28 amino acid residues from the NS1 polypeptide does not affect replication of the virus at permissive temperatures.

            Descriptors:  genes viral, influenza A virus avian genetics, RNA viral genetics, viral proteins genetics, base sequence, codon, mutation, RNA, messenger, temperature, viral nonstructural proteins.

Roditi, I.J. and J.S. Robertson (1984). Nucleotide sequence of the avian influenza virus A/Fowl Plague/Rostock/34 segment 1 encoding the PB2 polypeptide. Virus Research 1(1): 65-71.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Descriptors:  avian influenza virus, nucleotide sequence, RNA, polypeptide.

Roepke, D.C., S.M. Goyal, C.J. Kelleher, D.A. Halvorson, A.J. Abraham, R.F. Freitas, and E.L. Cussler (1987). Use of temperature-sensitive gel for concentration of influenza virus from infected allantoic fluids. Journal of Virological Methods 15(1): 25-31.  ISSN: 0166-0934.

            NAL Call Number:  QR355.J6

            Abstract:  Cross-linked, poly(N-isopropylacrylamide) gel was used to concentrate avian influenza virus from allantoic fluid. Placing the gel in virus-infected allantoic fluid at 4 degrees C caused the gel to swell and absorb small molecular weight solutes, while excluding avian influenza virus and other large particles. Warming the gel to 37 degrees C or more caused the gel to collapse. The gel remained functional after sterilization in an autoclave and could be reused to concentrate other samples of allantoic fluid. Using a combined concentration and elution technique, we were able to achieve an average of 84.2% virus recovery, while reducing the fluid volume from 90 ml to 7.6 ml.

            Descriptors:  allantois microbiology, fetal membranes microbiology, influenza A virus avian isolation and purification, acrylic resins, chick embryo, hydrogen-ion concentration, temperature.

Rogers, G.N. and B.L. D'Souza (1989). Receptor binding properties of human and animal H1 influenza virus isolates. Virology 173(1): 317-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  It has been previously reported that several human H1 influenza viruses isolated prior to 1956, in contrast to human H3 isolates which are quite specific for SA alpha 2,6Gal sequences, apparently recognize both SA alpha 2,3Gal and SA alpha 2,6Gal sequences (Rogers, G.N., and Paulson, J.C., Virology 127, 361-373, 1983). In this report human H1 isolates representative of two epidemic periods, from 1934 to 1957 and from 1977 to 1986, and H1 influenza isolated from pigs, ducks, and turkeys were compared for their ability to utilize sialyloligosaccharide structures containing terminal SA alpha 2,3Gal or SA alpha 2,6Gal sequences as receptor determinants. Five of the eight human isolates from the first epidemic period recognize both SA alpha 2,3Gal and SA alpha 2,6Gal linkages, in agreement with our previous results. Of the remaining three strains, all isolated towards the end of the first epidemic, two appear to prefer SA alpha 2,6Gal sequences while the third preferentially binds SA alpha 2,3Gal sequences. In contrast to the early isolates, 11 of 13 human strains isolated during the second epidemic period preferentially bind SA alpha 2,6Gal containing oligosaccharides. On the basis of changes in receptor binding associated with continued passage in the laboratory for some of these later strains, it seems likely that human H1 isolates preferentially bind SA alpha 2,6Gal sequences in nature, and that acquisition of SA alpha 2,3Gal-binding is associated with laboratory passage. Influenza H1 viruses isolated from pigs were predominantly SA alpha 2,6Gal-specific while those isolated from ducks were primarily SA alpha 2,3Gal-specific. Thus, as has been previously reported for H3 influenza isolates, receptor specificity for influenza H1 viruses appears to be influenced by the species from which they were isolated, human isolates binding preferentially to SA alpha 2,6Gal-containing oligosaccharides while those isolated from ducks prefer SA alpha 2,3Gal-containing oligosaccharides. However, unlike the SA alpha 2,6Gal-specific H3 isolates, binding to cell surface receptors by the H1 influenza viruses is not sensitive to inhibition by horse serum glycoproteins, regardless of their receptor specificity. These results suggest that, while the H1 and H3 hemagglutinins appear to be subject to similar host-derived selective pressures, there appear to be certain fundamental differences in the detailed molecular interaction of the two hemagglutinins with their sialyloligosaccharide receptor determinants.

            Descriptors:  influenza A virus avian metabolism, influenza A virus human metabolism, influenza A virus, porcine metabolism, influenza A virus metabolism, orthomyxoviridae metabolism, receptors, virus metabolism, ducks, hemagglutination inhibition tests, hemagglutination tests, species specificity, swine, turkeys.

Rogers, G.N. and J.C. Paulson (1983). Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127(2): 361-73.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The binding of influenza virus to erythrocytes and host cells is mediated by the interaction of the viral hemagglutinin (H) with cell surface receptors containing sialic acid (SA). The specificity of this interaction for 19 human and animal influenza isolates was examined using human erythrocytes enzymatically modified to contain cell surface sialyloligosaccharides with the sequence SA alpha 2,6Gal beta 1,4GlcNAc; SA alpha 2,3Gal beta 1,4(3)GlcNAc; SA alpha 2,3Gal beta 1,3GalNAc; or SA alpha 2,6GalNAc. Although none of the viruses agglutinated cells containing the SA alpha 2,6GalNAc linkage, differential agglutination of cells containing the other three sequences revealed at least three distinct receptor binding types. Several virus isolates exhibited marked receptor specificity, binding only to cells containing the SA alpha 2,6Gal or the SA alpha 2,3Gal linkage, while others bound equally well to cells containing either linkage. Moreover, some viruses could distinguish between two oligosaccharide receptor determinants containing the terminal SA alpha 2,3Gal linkage when present in the SA alpha 2,3Gal beta 1,4(3)GlcNAc sequence or the SA alpha 2,3Gal beta 1,3GalNAc sequence binding cells containing only the former. The observed receptor specificities were not significantly influenced by the viral neuraminidases as shown by the use of the potent neuraminidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Receptor specificity appeared, to some extent, to be dependent on the species from which the virus was isolated. In particular, human isolates of the H3 serotype all agglutinated cells containing the SA alpha 2,6Gal linkage, but not cells bearing the SA alpha 2,3Gal beta 1,3GalNAc sequence. In contrast, antigenically similar (H3) isolates from avian and equine species preferentially bound erythrocytes containing the SA alpha 2,3Gal linkage. This is of particular interest in view of the identification of the avian virus H3 hemagglutinin as the progenitor of the H3 hemagglutinin present on the current human Hong Kong viruses.

            Descriptors:  hemagglutinins viral, influenza A virus immunology, oligosaccharides metabolism, receptors, virus metabolism, hemagglutination, viral, hemagglutinin glycoproteins, influenza virus, influenza A virus avian immunology, influenza A virus human immunology, influenza A virus, porcine immunology, neuraminidase metabolism, species specificity.

Rogers, G.N., T.J. Pritchett, J.L. Lane, and J.C. Paulson (1983). Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants. Virology 131(2): 394-408.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Human and animal (avian and equine) influenza A virus isolates of the H3 serotype exhibit marked differences in their ability to bind specific sialyloligosaccharide sequences that serve as cell surface receptor determinants (G. Rogers and J. Paulson, 1983, Virology 127, 361-373). Whereas human isolates of this subtype strongly agglutinate enzymatically modified human erythrocytes containing the terminal SA alpha 2,6Gal sequence, avian and equine isolates preferentially agglutinate erythrocytes bearing the SA alpha 2, 3Gal sequence. As shown in this report, a glycoprotein found in horse serum, alpha 2-macroglobulin, is a potent inhibitor of viral adsorption to the cell surface for human H3 isolates. In contrast, avian and equine isolates are poorly inhibited suggesting a correlation between receptor specificity and inhibitor sensitivity. Growth of a human H3 isolate (A/Memphis/102/72) on MDCK cells in the presence of horse serum resulted in an overall shift in the virus receptor specificity from preferential binding of the SA alpha 2,6Gal linkage to preferential binding of the SA alpha 2,3Gal linkage characteristic of avian and equine isolates. Clonally isolated variants of A/Memphis/102/72 grown in the presence or absence of horse serum exhibited binding properties that account for those observed in the field isolates. Clones which preferentially bound the SA alpha 2,6Gal linkage, like the parent human virus, were very sensitive to inhibition of hemagglutination by horse serum and equine alpha 2-macroglobulin. In contrast, receptor variants which preferentially bound the SA alpha 2,3Gal linkage, like the avian and equine isolate, were insensitive to such inhibitors. None of the variants was very sensitive to inhibition of hemagglutination by human alpha 2-macroglobulin. These results suggest that the presence, in vivo, of a glycoprotein inhibitor such as equine alpha 2-macroglobulin could suppress infection of influenza viruses bearing an H3 hemagglutinin with a SA alpha 2,6Gal specific, inhibitor sensitive phenotype, allowing growth to predominance of a virus which is SA alpha 2,3Gal specific and inhibitor insensitive as found in avian and equine isolates.

            Descriptors:  glycoproteins antagonists and inhibitors, influenza A virus avian drug effects, influenza A virus human drug effects, influenza A virus drug effects, receptors, virus drug effects, viral proteins antagonists and inhibitors, adsorption, chick embryo, ducks, erythrocytes immunology, erythrocytes microbiology, hemagglutination inhibition tests, hemagglutination tests, hemagglutinins viral analysis, horses, alpha macroglobulins pharmacology.

Rohde, W., C.B. Boschek, E. Harms, R. Rott, and C. Scholtissek (1979). Characterization of virus-like particles produced by an influenza A virus. Archives of Virology 62(4): 291-302.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The influenza strain 413 1,1 segregated as a stable recombinant during passage of the isolate 19/N which was obtained after double infection of chick embryo fibroblasts by virus N and the fowl plague virus (FPV) mutant ts 19. Its gene constellation was determined by molecular hybridization. Upon infection of chick embryo cells by this recombinant strain, two particle populations of high (H) and low (L) buoyant densities were produced. By biological and biochemical parameters, the H-population (delta = 1.22 g/cm3) cannot be distinguished from standard infectious influenza virus. In contrast, the noninfectious L-particles (delta = 1.14 g/cm3) lack all virus-specific glycoproteins (HA, NA) as well as the matrix protein M and are visualized by electron microscopy as spikeless particles. Significant changes in the quantitative composition of the phospholipid bilayer are evident as compared to the H-particles. In addition to the previously characterized eight genes both populations contain a variety of smaller RNA fragments which hybridize with complementary RNA and presumably represent degradation products of full-length genes.

            Descriptors:  influenza A virus avian ultrastructure, phospholipids analysis, RNA viral analysis, viral proteins analysis, virion ultrastructure, chick embryo, fibroblasts, genes viral, influenza A virus avian genetics, influenza A virus avian growth and development, mutation, recombination, genetic, tissue culture, virus replication.

Rohde, W., E. Harms, and C. Scholtissek (1977). Biochemical studies on influenza viruses. I. Comparative analysis of equine 2 virus and virus N genes and gene products. Virology 79(2): 393-404.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus analysis, RNA viral analysis, translation, genetic, base sequence,  electrophoresis, polyacrylamide gel, horses, influenza A virus avian, influenza A virus isolation and purification, nucleic acid hybridization, recombination, genetic, viral proteins analysis.

Rohde, W. and C. Scholtissek (1980). On the origin of the gene coding for an influenze A virus nucleocapsid protein. Archives of Virology 64(3): 213-23.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The gene coding for the nucleocapsid protein NP of the influenza A virus recombinant strain 413 1,1 was characterized biochemically by molecular hybridization and fingerprint analysis. The data presented suggest that this NP gene has evolved by intracistronic recombination between NP genes of virus N and the fowl plague virus temperature-sensitive mutants ts 19.

            Descriptors:  capsid genetics, genes viral, influenza A virus avian genetics, RNA viral genetics, viral proteins genetics, avian analysis, mutation, nucleic acid hybridization, oligonucleotides analysis, peptides analysis, viral analysis, recombination, genetic, temperature, viral proteins analysis.

Rohm, C., T. Horimoto, Y. Kawaoka, J. Suss, and R.G. Webster (1995). Do hemagglutinin genes of highly pathogenic avian influenza viruses constitute unique phylogenetic lineages? Virology 209(2): 664-670.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Avian influenza A viruses of the H5 and H7 subtypes periodically cause severe outbreaks of disease in poultry. The question we wished to address in this study is whether these highly pathogenic strains constitute unique lineages or whether they and related nonpathogenic viruses are derived from common ancestors in the wild bird reservoir. We therefore compared the nucleotide and amino acid sequences of the hemagglutinin (HA) genes of 15 H5 and 26 H7 influenza A viruses isolated over 91 years from a variety of host species in Eurasia, Africa, Australia, and North America. Phylogenetic analysis indicated that the HA genes of H5 and H7 viruses that cause severe disease in domestic birds do not form unique lineages but share common ancestors with nonpathogenic H5 and H7 viruses. These findings predict that highly pathogenic avian H5 and H7 influenza A viruses will continue to emerge from wild bird reservoirs. Another important question is whether H7 influenza viruses found in mammalian species are derived from avian strains. We included eight equine influenza viruses and one seal isolate in the phylogenetic analysis of H7 HA genes. We could show that the HA genes of both, the equine and the seal viruses, shared ancestors with avian H7 HA genes. This indicates that currently circulating H7 viruses with an avian HA gene may have the potential to adapt to mammalian species and to cause an influenza outbreak in the new host.

            Descriptors:  avian influenza virus, agglutinins, genes, pathogenicity, phylogeny, nucleotide sequence, chemical composition, biological properties, cell structure, chromosomes, evolution, genomes, influenza virus, microbial properties, nucleus, orthomyxoviridae, proteins, viruses, viral hemagglutinins, structural genes, amino acid sequences.

Rohm, C., J. Suss, V. Pohle, and R.G. Webster (1996). Different hemagglutinin cleavage site variants of H7N7 in an influenza outbreak in chickens in Leipzig, Germany. Virology 218(1): 253-7.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The hemagglutinin (HA) genes from four avian H7N7 influenza A isolates, from a single outbreak, were shown to possess different cleavage sites that contain varying numbers of basic amino acid residues (KKKKR, KRKKR, KKRKKR, KKKKKKR). All four variants are highly pathogenic in chickens and share an immediate common ancestral HA with A/tern/Potsdam/342-6/79 (H7N7) and A/swan/Potsdam/63-6/81 (H7N7). These viruses are nonpathogenic and contain no extra basic amino acids at the cleavage site of their HA. During evolution a common precursor virus acquired different sequences at the cleavage site of the HA and became highly pathogenic in chickens. In vitro assays revealed that the HA from A/chicken/Leipzig/79 with KKKKR at the cleavage site was only partially cleaved (41%), compared to 93-100% cleavage of the other HAs. Since all four viruses were highly pathogenic in chickens, these findings confirm that the degree of pathogenicity in vivo is not exclusively determined by the degree of HA cleavability.

            Descriptors:  chickens, disease outbreaks veterinary, fowl plague virology, hemagglutinins viral metabolism, influenza A virus avian metabolism, amino acid sequence, base sequence, DNA, viral, fowl plague epidemiology, geese, Germany epidemiology, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, avian genetics, molecular sequence data, phylogeny.

Rohm, C., N. Zhou, J. Suss,  J. Mackenzie, and R.G. Webster (1996). Characterization of a novel influenza hemagglutinin, H15: criteria for determination of influenza A subtypes. Virology  217(2): 508-16.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Two viruses with a novel hemagglutinin (HA), A/duck/Australia/341/83 and A/shearwater/West Australia/2576/79, have been isolated from a duck and a shorebird in Australia. Hemagglutination inhibition and double immunodiffusion assays failed to reveal cross-reactivity with any of the known subtypes (H1 to H14). We therefore propose that these viruses constitute a new HA subtype, H15. Sequence analysis of the HA genes confirmed the serologic findings. When compared at the amino acid level, the HA1 region of the H15 subtype differs from those of the other subtypes by 30% and more. This degree of heterogeneity is also found among HA genes of other subtypes. Thus we propose that amino acid sequence data should be evaluated when determining the HA subtypes of influenza A viruses. Sequence comparison and phylogenetic analysis suggested that the HA subtype H15 is most closely related to the H7. Compared to the H7 HA, the H15 acquired a 30-nucleotide insertion within HA1 at position 253 which is located in the globular head of the molecule. This finding suggests that RNA recombination, although a rare event in nature, may play an important role in the evolution of influenza viruses.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian classification, influenza A virus classification, amino acid sequence, antigens, viral genetics, genes, structural, viral, hemagglutinins viral genetics, avian immunology, influenza A virus immunology, molecular sequence data, phylogeny, RNA viral genetics, sequence homology, amino acid, sequence homology, nucleic acid.

Romanos, M.A. and A.J. Hay (1984). Identification of the influenza virus transcriptase by affinity-labeling with pyridoxal 5'-phosphate. Virology 132(1): 110-7.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Pyridoxal 5'-phosphate (PLP), a reversible inhibitor of in vitro transcription by fowl plaque virus, has been used to identify the transcriptase. Kinetic analyses showed that PLP competitively inhibits the addition of each nucleoside triphosphate in ApG-primed reactions, suggesting that both initiation and elongation are affected. The irreversible inhibition by PLP following reduction with borohydride was prevented by preincubation with the first substrate: GTP in unprimed reactions or CTP in the presence of ApG. On reaction of FPV proteins with PLP and [3H]borohydride the core protein PB1 was preferentially labeled and the labeling was selectively blocked by GTP or ApG + CTP. These data suggest that PB1 has the nucleotide-binding site of the transcriptase, is responsible for both initiation and elongation, and is apparently associated with the 3' ends of template RNAs in virions.

            Descriptors:  influenza A virus avian enzymology, pyridoxal phosphate pharmacology, reverse transcriptase inhibitors, affinity labels, chick embryo, kinetics, transcription, genetic, viral core proteins, viral proteins metabolism.

Romero, P.A., R. Datema, and R.T. Schwarz (1983). N-methyl-1-deoxynojirimycin, a novel inhibitor of glycoprotein processing, and its effect on fowl plague virus maturation. Virology 130(1): 238-42.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The glucose analogue N-methyl-1-deoxynojirimycin was found to be a specific inhibitor of the trimming of the outermost glucose residue of the N-linked precursor-oligosaccharide Glc3Man9GlcNAc2, and therefore of oligosaccharide processing, in fowl plague virus-infected chicken-embryo cells. The fowl plague virus glycoproteins in N-methyl-1-deoxynojirimycin-treated cells contain oligosaccharides of the composition Glc3ManxGlcNAc2 (x = 7, 8, and 9). Inhibition of trimming of the outermost glucose residues does not prevent release of infectious virus with oligosaccharides of the composition Glc3Man7(GlcNAc)2. On the other hand inhibition of the trimming of the innermost glucose residue does inhibit release of infectious virus (Datema, R., Romero, P. A., Legler, G., and Schwarz, R. T. Proc. Nat. Acad. Sci. USA 79, 6787-6791 (1982) ).

            Descriptors:  1 deoxynojirimycin analogs and derivatives, anti bacterial agents pharmacology, antiviral agents pharmacology, glucosamine analogs and derivatives, glycoproteins antagonists and inhibitors, influenza A virus avian drug effects, viral proteins antagonists and inhibitors, chick embryo, glucosamine pharmacology, avian metabolism, oligosaccharides antagonists and inhibitors, virion drug effects, virion metabolism.

Ronda, E., A. Garcia Gancedo, L. Alonso, P. Vilas, and L. Lucas (1966). Killed fowl plague virus vaccine obtained from chick embryo cells. Microbiologia Espanola 19(3): 257-80.  ISSN: 0026-2595.

            NAL Call Number:  448.3 M583

            Descriptors:  influenza A virus avian, viral vaccines, virus cultivation, chick embryo, chickens, HeLa cells, orthomyxoviridae infections immunology, tissue culture, vaccination.

Rosenbergova, M., E. Matisova, and S. Pristasova (1971). Endonuclease activities of myxo- and paramyxoviruses. Acta Virologica 15(6): 515-8.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  influenza A virus avian enzymology, Newcastle disease virus enzymology, orthomyxoviridae enzymology, parainfluenza virus 1, human enzymology, centrifugation, density gradient, chick embryo, chlorides, hydrogen-ion concentration, avian metabolism, magnesium, Newcastle disease virus metabolism, orthomyxoviridae metabolism, parainfluenza virus 1, human metabolism, perchloric acid, phosphorus isotopes, precipitation, RNA, ribosomal analysis, ribosomal metabolism, ribonucleases metabolism, solubility, sucrose, temperature.

Rosenbergova, M. and S. Pristasova (1972). Nuclease activity of large RNA viruses. Acta Virologica 16(1): 1-8.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Descriptors:  leukosis virus, avian enzymology, orthomyxoviridae enzymology, ribonucleases metabolism, carcinoma, ehrlich tumor, cattle, chick embryo, DNA metabolism, deoxyribonucleases metabolism, influenza A virus avian enzymology, leukosis virus, avian isolation and purification, Newcastle disease virus enzymology, nucleic acid denaturation, orthomyxoviridae isolation and purification, parainfluenza virus 1, human enzymology, paramyxoviridae enzymology, paramyxoviridae isolation and purification, polynucleotides metabolism, RNA, neoplasm isolation and purification, neoplasm metabolism, species specificity, temperature, thymus gland, tissue culture, virus cultivation.

Rott, R. (1980). Genetic determinants for infectivity and pathogenicity of influenza viruses. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 288(1029): 393-9.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  The objective of the studies presented was to define a molecular basis for infectivity and pathogenicity of influenza virus. It is demonstrated that activation of the HA glycoprotein by post-translational proteolytic cleavage is indispensable for the formation of infectious influenza virus. There are two preconditions for influenza virus to be pathogenic: (1) the presence on the virus particle of a cleaved HA molecule essential for the infectivity, and (2) an optimal genome composition. In naturally occurring avian influenza viruses there is a direct correlation between the cleavability of the haemagglutinin, the potential of the virus to be produced in infectious form in a wide range of host cells, and the viruses' pathogenicity for chicken. It is concluded that Nature selects an optimal gene constellation for each individual field strain. In these viruses the structure of the haemagglutinin is the determining factor for pathogenicity.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, avian pathogenicity, protein precursors metabolism, structure activity relationship, viral proteins genetics.

Rott, R. (1985). In vitro Differenzierung von pathogenen und apathogenen aviaren Influenzaviren. [In vitro differentiation of pathogenic and nonpathogenic avian influenza viruses]. Berliner Und Munchener Tierarztliche Wochenschrift 98(2): 37-9.  ISSN: 0005-9366.

            NAL Call Number:  41.8 B45

            Descriptors:  influenza A virus avian classification, microbiological techniques veterinary, chick embryo, fibroblasts, hemagglutination tests, avian pathogenicity, plaque assay veterinary, tissue culture, virulence, virus cultivation.

Rott, R. (1992). The pathogenic determinant of influenza virus. Veterinary Microbiology 33(1-4): 303-10.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  Influenza viruses, like other viruses, must exhibit a genome constellation, which permits optimal virus reproduction in a given host. Besides this prerequisite the influenza virus haemagglutinin glycoprotein (HA) has been shown to be an essential determinant for pathogenicity. HA, which is synthesized as a precursor molecule, is activated by posttranslational cleavage by host proteases to obtain its full biological properties. Proteolytic activation is therefore indispensable for effective virus spread in the infected host and thus for pathogenicity. HA of the highly pathogenic avian influenza viruses inducing a systemic infection in birds is cleaved in a broad range of different host cells. On the other hand, HA of all mammalian viruses and the nonpathogenic avian strains, which cause local infection, exhibit a restricted cleavability. The prime determinant for these differences has been found to be the structure of the cleavage site. This concept was corroborated on virus mutants adapted in vitro to a new host.

            Descriptors:  hemagglutinins viral immunology, orthomyxoviridae pathogenicity, viral envelope proteins immunology, amino acid sequence, base sequence, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral chemistry, hemagglutinins viral genetics, molecular sequence data, mutagenesis, insertional, orthomyxoviridae genetics, orthomyxoviridae immunology, RNA, ribosomal, 28S chemistry, viral envelope proteins chemistry, viral envelope proteins genetics.

Rott, R. (1977). The structural basis of the function of influenza virus glycoproteins. Medical Microbiology and Immunology 164(1-3): 23-33.  ISSN: 0300-8584.

            Descriptors:  hemagglutinins viral analysis, neuraminidase analysis, neuraminidase immunology, orthomyxoviridae enzymology, glycopeptides analysis, influenza A virus avian enzymology, avian immunology, avian ultrastructure.

Rott, R., H. Becht, and Orlich (1975). Antigenic relationship between the surface antigens of avian and equine influenze viruses. Medical Microbiology and Immunology 161(4): 253-61.  ISSN: 0300-8584.

            Abstract:  Influenza virus Equine 1 (A/equine/Prague/56) has a hemagglutinin which is antigenically related to the hemagglutinin of fowl plague virus strain Rostock (FPV) and a neuraminidase which cross-reacts with the enzyme of virus N (A/chick/Germany/49). After a single injection of chickens with Equine 1 virus no hemagglutination inhibiting (HI) and neutralizing antibodies against FPV can be demonstrated, although the birds are fully protected against a lethal dose of FPV. HI and neutralizing antibodies against FPV appear after a second injection of Equine 1 virus several weeks after the first one. Liberation of newly sunthesized FPV from the host cell is ingibited by antibodies cross-reacting with any antigen of virus surface.

            Descriptors:  antigens, viral administration and dosage,  arteritis virus, equine immunology, influenza A virus avian immunology, RNA viruses immunology, binding sites, antibody, epitopes, fluorescent antibody technique, hemadsorption, hemagglutination inhibition tests, hemagglutination tests, hemagglutinins viral isolation and purification, injections, intravenous, neuraminidase analysis, neutralization tests, plaque assay.

Rott, R., H. Becht, and M. Orlich (1974). The significance of influenza virus neuraminidase in immunity. Journal of General Virology 22(1): 35-41.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  antibody formation, antigens, viral, fowl plague immunology, influenza A virus avian immunology, neuraminidase analysis, orthomyxoviridae immunology, chickens immunology, hemagglutination inhibition tests, hemagglutinins viral analysis, immune sera, immunization, influenza veterinary, avian enzymology, neutralization tests, orthomyxoviridae enzymology, rabbits immunology, swine, swine diseases microbiology.

Rott, R. and H.D. Klenk (1973). Biosynthese des Hamagglutinins eines Influenzavirus (Virus der Klassischen Geflugelpest. [Hemagglutinin biosynthesis in an influenza virus (fowl plague virus)]. Zentralblatt Fur Veterinarmedizin. Reihe B Journal of Veterinary Medicine. Series B 20(7): 509-21.  ISSN: 0514-7166.

            NAL Call Number:  41.8 Z52

            Descriptors:  antibodies, viral biosynthesis, hemagglutination tests, influenza A virus avian immunology, chickens, tissue culture, virus cultivation.

Rott, R., H.D. Klenk, and C. Scholtissek (1984). Bedeutung des Hamagglutinins fur die Pathogenitat aviarer Influenzaviren. [Significance of hemagglutinins for the pathogenicity of avian influenza viruses]. Zentralblatt Fur Bakteriologie, Mikrobiologie, Und Hygiene. Series A, Medical Microbiology, Infectious Diseases, Virology, Parasitology 258(2-3): 337-49.  ISSN: 0176-6724.

            NAL Call Number:  448.3 C33 (1)

            Abstract:  In addition to acute viral diseases, persistent infections have attained considerable interest in recent years. Such persistent infections are characterized by extended time periods in which the infecting virus remains within the organism before the eventual appearance of manifest symptoms. These infections may be evoked by a variety of virus species resulting in a diversity of pathogenic reactions and clinical manifestations. The mechanisms of viral persistence, where known, also appear to be quite diverse. As far as space permits, some examples of persistent infections will be presented and the mechanisms of the pathogenesis of the resulting diseases will be discussed.

            Descriptors:  hemagglutinins viral analysis, hemagglutinins viral genetics, hemagglutinins viral immunology, influenza A virus avian pathogenicity, amino acid sequence, cell membrane microbiology, chick embryo, fetal membranes microbiology, genes viral, avian genetics, avian growth and development, avian ultrastructure, models, molecular, mutation, virulence.

Rott, R., M. Orlich, and C. Scholtissek (1976). Attenuation of pathogenicity of fowl plague virus by recombination with other influenza A viruses nonpathogenic for fowl: nonexculsive dependence of pathogenicity on hemagglutinin and neuraminidase of the virus. Journal of Virology 19(1): 54-60.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  A number of antigenic hybrids of influenza A viruses were produced possessing either the hemagglutinin or the neuraminidase of fowl plague virus and the corresponding antigen derived from another influenza A virus. Other recombinants were obtained carrying both surface antigens of fowl plague virus but differing from the parent in certain biological properties. None of the recombinants isolated were pathogenic for adult chickens. Most recombinants obtained after crosses between reciprocal recombinants carrying both fowl plague virus surface antigens were also apathogenic for chickens. Using the same parent recombinants for double infection some of the progeny "back-recombinants" were pathogenic, whereas others were not. From these results it is concluded that the surface components do not by themselves determine the pathogenicity of influenza A viruses.

            Descriptors:  hemagglutinins viral analysis, influenza A virus avian pathogenicity, neuraminidase immunology, orthomyxoviridae pathogenicity, recombination, genetic, chick embryo, crosses, genetic, avian enzymology, avian immunology, neuraminidase analysis, orthomyxoviridae enzymology, orthomyxoviridae immunology.

Rott, R., M. Orlich, and C. Scholtissek (1979). Correlation of pathogenicity and gene constellation of influenza A viruses. III. Non-pathogenic recombinants derived from highly pathogenic parent strains. Journal of General Virology 44(2): 471-7.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  We have demonstrated by recombination of two highly pathogenic avian influenza viruses [A/FPV/Rostock (Hav1N1) x A/turkey/England/63 (Hav1Nav3)] that recombinants can be isolated which are pathogenic as well as non-pathogenic for chickens. They carried the glycoproteins of either parent strains, and all are produced in infectious form in chick embryo cells. Genetic analysis revealed that the non-pathogenic recombinants possess a mixed RNA polymerase complex, consisting of pol 1, pol 2, ptra and NP gene products, while, with one exception, the pathogenic recombinants have the genes coding for the polymerase activity from one or other parent virus. The biological properties of the recombinant viruses did not correlate with their pathogenicity for chickens.

            Descriptors:  genes viral, influenza A virus avian genetics, recombination, genetic, chickens, DNA directed RNA polymerases genetics, fowl plague microbiology, avian pathogenicity, neuraminidase genetics, turkeys.

Rott, R., M. Orlich, and C. Scholtissek (1982). Differences in the multiplication at elevated temperature of influenza virus recombinants pathogenic and nonpathogenic for chicken. Virology 120(1): 215-24.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  chickens microbiology, influenza A virus avian pathogenicity, recombination, genetic, cell line, chick embryo, DNA directed RNA polymerases genetics, genes viral, avian genetics, avian growth and development, plaque assay, temperature.

Rott, R., M. Orlich, and C. Scholtissek (1981). Intrinsic interference between swine influenza and fowl plague virus. Archives of Virology 69(1): 25-32.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Multiplication of swine influenza (SW) virus is inhibited by fowl plaque virus (FPV) at the level of RNA synthesis when host cells are infected with both viruses at a high multiplicity of infection. Under these conditions reassortment between the two viruses cannot be detected. The inhibitory effect of FPV is highly reduced and recombinants between the two viruses could be obtained when the cells were superinfected with FPV 1--2 hours after infection with SW virus, or after simultaneous infection with a low multiplicity of infection. The phenomenon is compatible with the intrinsic interference.

            Descriptors:  influenza A virus avian growth and development, porcine growth and development, influenza A virus growth and development, viral interference, antigens, viral genetics, cell line, chick embryo, dogs, hybridization, genetic, avian genetics, porcine genetics, kidney, tissue culture, virus replication.

Rott, R., M. Reinacher, M. Orlich, and H.D. Klenk (1980). Cleavability of hemagglutinin determines spread of avian influenza viruses in the chorioallantoic membrane of chicken embryo.  Archives of Virology 65(2): 123-33.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The spread of infection in the chorioallantoic membrane (CAM) has been analysed with pathogenic and non-pathogenic avian influenza A viruses. After allantoic inoculation of pathogenic strains, high titers of infectious virus were found in the allantoic fluid, and virus growth could be demonstrated by immunohistology and electron microscopy in the allantoic epithelium, the mesenchyma, and in the chorionic epithelium. By the same route of inoculation, non-pathogenic strains yielded also higher titers of infectious virus in the allantoic fluid, but virus replication was restricted to the allantoic epithelium and did not occur in the other cell layers. After chorionic inoculation of pathogenic strains, replication occurred in all layers of the CAM, and infectious virus was released into the allantoic fluid. However, when the chorionic epithelium was infected with a non-pathogenic strain, infection did not spread beyond the site of inoculation. These differences in virus spread are based on differential activation of the hemagglutinin by proteolytic cleavage. The hemagglutinin of pathogenic strains is cleaved in cells of each layer, whereas the hemagglutinin of non-pathogenic strains is cleaved only in the allantoic epithelium. In epithelial cells, virus budding occurred nearly exclusively at the apical side of the cell surface, but this polarization of virus maturation was found with both pathogenic and nonpathogenic strains, indicating that it does not account for the differences in virus spread and, thus, in pathogenicity.

            Descriptors:  fetal membranes microbiology, hemagglutinins viral, influenza A virus avian growth and development, virus replication, allantois microbiology, chick embryo, chorion microbiology, epithelium microbiology, avian immunology, avian pathogenicity, tissue culture, virulence.

Rott, R. and C. Scholtissek (1968). Biochemical studies on influenza virus multiplication at reduced temperatures. Journal of General Virology 3(2): 239-45.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian, virus replication, carbon isotopes, complement fixation tests, cycloheximide pharmacology, cytopathogenic effect, viral, neuraminidase metabolism, RNA biosynthesis, temperature, tissue culture, uridine metabolism.

Rott, R. and C. Scholtissek (1967). Multiplication of myxoviruses. Modern Trends in Medical Virology 1(0): 25-48.  ISSN: 0544-6856.

            Descriptors:  orthomyxoviridae growth and development, virus replication, antigens, viral, chick embryo, DNA biosynthesis, dactinomycin pharmacology, defective viruses, hemagglutinins viral, inclusion bodies, viral, influenza A virus avian growth and development, neuraminidase biosynthesis, neuraminidase pharmacology, Newcastle disease virus growth and development, phagocytosis, RNA viral biosynthesis, viral proteins biosynthesis.

Rott, R. and C. Scholtissek (1970). Specific inhibition of influenza replication by alpha-amanitin. Nature 228(5266): 56.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Descriptors:  mycotoxins pharmacology, orthomyxoviridae drug effects, virus replication drug effects, depression, chemical, influenza A virus avian, leucine metabolism, Newcastle disease virus, orthomyxoviridae metabolism, RNA viral biosynthesis, tritium, uridine metabolism, viral proteins biosynthesis.

Rousset, J., M. Cherbonnel, M.O. Le Bras, and V. Jestin (2003). Experimental challenge model with low pathogenic H7N1 avian influenza virus to assess protection against infection by these viruses. British Poultry Science 44(5): 830-1.  ISSN: 0007-1668.

            NAL Call Number:  47.8 B77

            Descriptors:  avian influenza virus, low pathogenic H7N1, experimental challenge, model, protection.

Rovnova, Z.I., E.I. Isaeva, A.L. Platonova, and P.N. Kosiakov (1989). Antigenno-geneticheskie sviazi virusov grippa cheloveka i zhivotnykh. [Antigenic-genetic connections between human and animal influenza viruses]. Voprosy Virusologii 34(5): 553-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A comparative immunological analysis of the composition of antigenic determinants (AGD) in hemagglutinins of human influenza A virus (HIAV) of the serosubtypes H1, H2, H3, and in hemagglutinins of animal influenza viruses (AIV) of the serosubtypes H1, H3-H6, H8-H11 with 25 polyclonal highly active sera was demonstrated. Using original monospecific mon AGD in HIAV and AIV hemagglutinins was demonstrated. Using original monospecific antibodies to individual AGD, those AGD contributing to similarity and differences between HIAV and AIV were determined. It was found that influenza A. virus strains isolated from man in the USSR in 1986 were identical in the antigenic structure of hemagglutinin with that isolated from a tern in 1973 (A/tern/Turkmenistan/18/73).

            Descriptors:  epitopes, genes viral, influenza A virus avian immunology, human immunology, antigens, viral immunology, cross reactions, hemagglutination tests, hemagglutinins viral genetics, hemagglutinins viral immunology, avian genetics, human genetics, neuraminidase genetics, neuraminidase immunology, species specificity.

Rudneva, I.A., V.P. Kovaleva, N.L. Varich, V.R. Farashyan, L.V. Gubareva, S.S. Yamnikova, I.A. Popova, V.P. Presnova, and N.V. Kaverin (1993). Influenza A virus reassortants with surface glycoprotein genes of the avian parent viruses: effects of HA and NA gene combinations on virus aggregation. Archives of Virology 133(3-4): 437-50.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A series of 33 human-avian and human-mammalian influenza virus reassortant clones possessing either HA or both HA and NA genes of the avian or mammalian virus was obtained by crosses of A/USSR/90/77 (H1N1) human virus with 5 avian and 1 mammalian influenza virus strains. All of the reassortants possessing NA genes of the H1N1 human parent virus and HA gene of an avian or mammalian parent virus had high values of infectivity/HA activity ratio. Since this feature could result from a limited virion aggregation, several reassortants were analyzed by velocity sucrose gradient centrifugation. In all cases tested, the reassortants of H3N1, H4N1, H10N1 and H13N1 composition were shown to be aggregated, whereas the preparations of the parent H1N1 virus and the reassortants possessing both HA and NA genes from the avian parents were represented mostly by single virions. The aggregates were formed at 4 degrees C and dissociated at 37 degrees C. The dissociation was blocked by an inhibitor of neuraminidase activity (2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid). The dissociation was reversible since the virions reaggregated at 4 degrees C; however, treatment with bacterial neuraminidase led to an irreversible dissociation of the aggregates. The tendency of the reassortants to aggregate correlates with an increased infectivity/HA ratio. No regular decrease in the neuraminidase activity in the virions of reassortants as compared to the parent H1N1 virus was revealed. The most likely explanation of the observed phenomenon seems to be an inefficient removal of sialic acid residues from the avian virus hemagglutinin by the human virus N1 neuraminidase.

            Descriptors:  influenza A virus genetics, membrane glycoproteins genetics, reassortant viruses genetics, viral proteins genetics, chick embryo, chickens, ducks, electrophoresis, polyacrylamide gel, genes viral, hemagglutination, viral, hemagglutinins viral genetics, avian genetics, avian physiology, human genetics, human physiology, influenza A virus physiology, neuraminidase genetics, neuraminidase pharmacology, RNA viral analysis, reassortant viruses physiology, recombination, genetic drug effects, temperature, whales.

Rudneva, I.A., N.L. Varich, N.V. Makarova, E.A. Kropotkina, and S.S. Iamnikova (2000). Gennyi analiz i fenotipicheskaia kharakteristika vysokoreproduktivnykh reassortantov, soderzhashchikh gen gemaggliutinina virusa grippa ptits podtipa H2. [Gene analysis and phenotypic characteristic of highly-reproductive reassortants, containing the gene for bird influenza virus subtype H2 hemagglutinin]. Voprosy Virusologii 45(1): 20-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A series of reassortant clones with antigenic formulae H2N1 and H2N3 were produced by genetic reassortment performed with the use of an avian influenza virus, A/Pintail Duck/Primorie/695/76 (H2N3) and a high-yield reassortant strain X-67. Preliminary identification of the parent origin of NP and NS genes for 5 reassortants was performed by comparison of the mobilities of virus-specific proteins in polyacrylamide gel electrophoresis. The parent origin of genes of internal and nonstructural proteins for 3 reassortants was identified by partial sequencing. Although the genes of internal and nonstructural proteins of the reassortants originated from high-yield X-67 virus, only H2N3 reassortants were similar to the high-yield parent virus as concerns the level of the virus accumulation evaluated by hemagglutination titration and measurement of the virus protein content.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, reassortant viruses genetics, birds, electrophoresis, polyacrylamide gel, phenotype.

Rudneva, I.A., N.L. Varich, N.V. Makarova, Y.A. Kropotkina, and S.S. Yamnikova (2000). Gene analysis and phenotypical characteristics of highly productive reassortants containing hemagglutinin gene of subtype H2 avian influenza virus. Voprosy Virusologii 45(1): 20-24.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A series of reassortant clones with antigenic formulae H2N1 and H2N3 were produced by genetic reassortment performed with the use of an avian influenza virus, A/Pintail Duck/Primorie/695/76 H2N3) and a high-yield reassortant strain X-67. Preliminary identification of the parent origin of NP and NS genes for 5 reassortants was performed by comparison of the mobilities of virus-specific proteins in polyacrylamide gel electrophoresis. The parent origin of genes of internal and nonstructural proteins for 3 reassortants was identified by partial sequencing. Although the genes of internal and nonstructural proteins of the reassortants originated from high-yield X-67 virus, only H2N3 reassortants were similar to the high-yield parent virus as concerns the level of the virus accumulation evaluated by hemagglutination titration and measurement of the virus protein content.

            Descriptors:  molecular genetics, gene analysis analytical method, genetic reassortment phenotypes, viral genetics.

Russell, R.J., S.J. Gamblin, L.F. Haire, D.J. Stevens, B. Xiao, Y. Ha, and J.J. Skehel (2004). H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes. Virology  325(2): 287-96.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Comparing the structures of H3, H5 and H9 subtype haemagglutinins, we deduced a structural basis for including all 15 influenza subtypes in four clades. H3, H5 and H9 represent three of these clades; we now report the structure of an H7 HA as a representative of the fourth clade. We confirm the structure of the turn at the N-terminus of the conserved central alpha-helix of HA2, and the combination of ionisable residues near the "fusion peptide" as clade-specific features. We compare the structures of three H1 HAs with H5 HA in the same clade, to refine our previous classification and we confirm the division of the clades into two groups of two. We also show the roles of carbohydrate side chains in the esterase-fusion domain boundaries in the formation of clade-specific structural markers.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, hemagglutinin glycoproteins, influenza virus classification, influenza A virus chemistry, influenza A virus classification, amino acid sequence, carbohydrates chemistry, crystallography, x-ray, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus genetics, models, molecular, molecular sequence data, phylogeny, protein structure, quaternary, protein structure, tertiary, sequence homology, amino acid.

Russi Cahill, J.C., M.C. Mogdasy, R.E. Somma Moreira, and M.H. de Peluffo (1975). Counterimmunoelectrophoresis with influenza antigens. I. Use of avian plague virus to detect type-specific antibodies to influenza A in human sera. Journal of Infectious Diseases 131(1): 64-6.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Avian plague virus was used as antigen in a counterimmunoelectrophoresis technique. This virus was selected because it detects only type-specific influenza A antibodies in human sera, avoiding the possible interference of other antigens with anodic migration. The results with reference sera, as well as the correlation of positive sera found by counterimmunoelectrophoresis and complement fixation with the proposed antigen, in the absence of other types of antibodies to fowl plague virus antigen, support the conclusion that the counterimmunoelectrophoresis technique reveals type-specific antibodies. The test is more sensitive than immunodiffusion but less sensitive than complement fixation. Its sensitivity, simplicity, and rapidity make it suitable for serologic surveys of human influenza A.

            Descriptors:  antibodies, viral analysis, antigens, viral, immunoelectrophoresis, influenza immunology, influenza A virus avian immunology, antibody specificity, chick embryo, complement fixation tests, guinea pigs immunology,  immune sera, immunodiffusion.

Ruttkayova Nedecka, S. and G. Russ (1977). Effect of a proteolytic enzyme inhbitor on influenza virus replication. Acta Virologica 21(1): 79-81.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  N-tosyl-L-phenylalanyl chloromethane patially inhibited the multiplicatiion of fowl plague virus (FPV) in infected cells. The capacity of the inhibitor to suppress the muliplication of FPV depended on the host cell system.

            Descriptors:  influenza A virus avian drug effects, virus replication drug effects, cultured cells, avian growth and development, tosylphenylalanyl chloromethyl ketone pharmacology.

Sadykhova, F.E. (1982). Antitela k virusam grippa u ptits. [Antibodies to influenza viruses in poultry]. Voprosy Virusologii 27(2): 218-20.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Determination of antibodies to influenza viruses in chicken sera by radial hemolysis technique using normal horse serum as the source of complement is described. This test was shown to be also very sensitive and standard with mammal sera when some strains, including the A/Khabarovsk/77, were tested.

            Descriptors:  antibodies, viral analysis, chickens immunology, influenza A virus immunology, hemolytic plaque technique, influenza A virus avian immunology, Newcastle disease virus immunology.

Saito, T., Y. Kawaoka, and R.G. Webster (1993). Phylogenetic analysis of the N8 neuraminidase gene of influenza A viruses. Virology 193(2): 868-76.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Phylogenetic analysis of the N8 neuraminidase (NA) genes from 18 influenza A viruses, representing equine and avian hosts in different geographic locations, revealed three major lineages: (i) currently circulating equine 2 viruses; (ii) avian viruses isolated in the Eurasian region, including A/Equine/Jilin/1/89, a recent avian-like N8 isolate found in horses in China; and (iii) avian viruses isolated in North America. Comparison of mutation rates indicated that avian N8 genes have evolved more slowly than their equine counterparts. That is, in both avian lineages, 72% of the nucleotide changes were silent in the terminal branches of the phylogenetic tree, whereas in equine 2 viruses, 59% of the nucleotide changes were silent. This suggests greater selective pressure on the NA gene from the mammalian immune system, leading to progressive evolution. Alternatively, the slower mutation rate for avian N8 genes could reflect a selective advantage gained from a longer, continuous span of evolution. The shape of the phylogenetic tree, the evolutionary rate, and the calculated date of origin for the N8 equine 2 virus lineage were comparable to findings for the equine 2 virus hemagglutinin (HA) gene (Bean et al., J. Virol. 66, 1129-1138, 1992). This suggests that both viral membrane glycoproteins of equine 2 viruses have evolved together and have been subjected to similar levels of selective pressure. Several amino acid residues were found to differ among the three host-specific lineages, but they may not be involved in host restriction of the NA, as they are shared by EQ/Jilin/1/89 and viruses of avian origin. The present findings complement detailed structural information on the N2 and N9 subtypes and should prove valuable in understanding future X-ray diffraction studies of N8 crystals.

            Descriptors:  genes, structural, viral, influenza A virus genetics, neuraminidase genetics, phylogeny, amino acid sequence, base sequence, cloning, molecular, ducks, Escherichia coli genetics, horses, influenza A virus avian classification, avian enzymology, avian genetics, influenza A virus classification, influenza A virus enzymology, models, molecular, molecular sequence data, mutation, neuraminidase chemistry, protein structure, secondary, RNA viral genetics, RNA viral isolation and purification, sequence homology, amino acid, sequence homology, nucleic acid.

Saito, T., W. Lim, and M. Tashiro (2004). Attenuation of a human H9N2 influenza virus in mammalian host by reassortment with an avian influenza virus. Archives of Virology 149(7): 1397-407.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  In order to develop a surrogate virus strain for production of an inactivated influenza vaccine against a human H9N2 virus, A/Hong Kong/1073/99 (HK1073: H9N2) was co-infected in embryonated chicken eggs with an apathogenic avian influenza virus, A/Duck/Czechoslovakia/56 (Dk/Cz: H4N6), for gene segment reassortment. Multiple-gene reassortants obtained were examined for replication in mammalian hosts in vitro and in vivo by infecting MDCK cells and by intranasal administration to hamsters, respectively. A 2-6 gene reassortant with both surface glycoproteins of HK1073 origin and the rest of Dk/Cz origin, HK/CZ-13, was shown to replicate poorly in the mammalian hosts both in vivo and in vitro comparing with HK1073, although this reassortant replicated as efficiently as each parental strain in embryonated eggs. No sequence difference was observed in the HA1 region between HK1073 and HK/CZ-13, indicating that the reassortant would be equivalent in its immunogenicity to the parental HK1073 strain when it is used as an inactivated vaccine. A virus strain with attenuation in mammalian hosts is preferable for production of an H9 vaccine, since it should reduce the risk of manufacturing-related infections of employees during the vaccine production. HK/CZ-13 can therefore be a surrogate strain for production of an inactivated vaccine as well as diagnostic antigens in case of a possible future pandemic caused by an HK1073-like H9 influenza virus.

            Descriptors:  influenza A virus, avian genetics, human genetics, influenza vaccines, reassortant viruses genetics, reassortant viruses physiology, administration, intranasal, cell line, chick embryo, DNA complementary chemistry, DNA complementary isolation and purification, hamsters, hemagglutinin glycoproteins, influenza virus immunology, avian pathogenicity, avian physiology, human pathogenicity, human physiology, mesocricetus, neuraminidase immunology, RNA, viral isolation and purification, viral metabolism, reassortant viruses immunology, reassortant viruses pathogenicity, reverse transcriptase polymerase chain reaction, sequence analysis, specific pathogen free organisms, vaccines, attenuated, virus replication.

Saito, T., G. Taylor, W.G. Laver, Y. Kawaoka, and R.G. Webster (1994). Antigenicity of the N8 influenza A virus neuraminidase: existence of an epitope at the subunit interface of the neuraminidase. Journal of Virology 68(3): 1790-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To locate antigenic epitopes on the N8 neuraminidase (NA), we generated a panel of 97 monoclonal antibodies (MAbs), 66 of which inhibited NA activity (NI antibodies). Three groups of NI MAbs were identified from their different reactivities with escape mutants. Group 1 antibodies recognized the peptide loop containing residues 344 to 346, which appears to be an immunodominant region on the rim of the enzyme center of the N8 NA. Group 2 antibodies recognized a novel epitope containing residues 150, 199, 367, 399, and 400 (N2 numbering). From the location of these residues on the three-dimensional structure of the N8 NA, the epitope appears to be located at the interface of two adjacent monomers in the tetrameric NA, one contributing residues 150 and 199 and the other contributing residues 367 and 399 to 400. The available evidence indicates that the MAbs of this group react with the NA only after it is fully assembled. The third group of antibodies recognized the peptide loops containing residues 367 and 399 to 400. All of the amino acid substitutions in N8 escape mutants which affect the NI activity of antibodies were located in the peptide loops known to form epitopes in the N2 and N9 subtypes, indicating that antigenic regions in the NA head inducing NI antibodies appear to be similar among different subtypes of influenza A viruses. The MAbs used in this study will be valuable in studying the role of each N8 NA epitope in host immune defense systems and in the kinetics analysis of the biosynthesis of the enzyme.

            Descriptors:  antibodies, viral immunology, epitopes immunology, influenza A virus avian immunology, neuraminidase immunology, amidohydrolases metabolism, antibodies, monoclonal, antibodies, viral classification, base sequence, avian enzymology, avian genetics, models, molecular, molecular sequence data, mutation genetics, precipitin tests, sequence analysis, structure activity relationship.

Saito, T., G. Taylor, and R.G. Webster (1995). Steps in maturation of influenza A virus neuraminidase. Journal of Virology 69(8): 5011-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  We have studied the maturation of the influenza A virus neuraminidase (NA), using monoclonal antibodies (MAbs) with different conformational specificities against the head domains of the N8 NA. The results obtained with radioimmunoprecipitation, together with previously published information, suggest the following steps in maturation of this molecule. First, the folding of the nascent NA leads to formation of the epitope recognized by MAb N8-10, a step that depends on the formation of intramolecular disulfide bonds. Second, monomers form dimers by an intermolecular disulfide linkage in the stalk, with a t1/2 of 2.5 min. Third, the epitope recognized by MAb N8-82 appears after dimerization, suggesting that oligomeric NAs may undergo conformational change with a t1/2 of 8 min. Finally, a tetramer-specific epitope recognized by MAb N8-4 appears on the NA with a t1/2 of 13 min. Epitope detection by MAb N8-4 was inhibited by tunicamycin treatment, suggesting that glycosylation of this molecule is required for proper tetramerization. Each of these proposed steps occurs in the endoplasmic reticulum of host cells, as demonstrated by treatment of virus-infected cells with brefeldin A or carbonyl cyanide m-chlorophenylhydrazine; subsequently, tetrameric NA is transported to the Golgi apparatus, where oligosaccharide processing is completed. Our findings also provide a possible explanation--lack of a functionally active conformation--for the absence of enzymatic function by NA monomers.

            Descriptors:  influenza A virus avian enzymology, neuraminidase metabolism, protein processing, post translational, antibodies, monoclonal immunology, antibody specificity, cell line, disulfides metabolism, dogs, epitopes immunology, glycosylation, kinetics, neuraminidase immunology, protein folding, temperature.

Sambhara, S., A. Kurichh, R. Miranda, T. Tumpey, T. Rowe, M. Renshaw, R. Arpino, A. Tamane, A. Kandil, O. James, B. Underdown, M. Klein, J. Katz, and D. Burt (2001). Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function. Cellular Immunology 211(2): 143-53.  ISSN: 0008-8749.

            NAL Call Number:  QR180.C4

            Descriptors:  iscoms immunology, influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine immunology, macrophages immunology, T lymphocytes, cytotoxic immunology, antibodies, viral immunology, cross reactions, fowl plague prevention and control, influenza immunology, mice inbred BALB c, mice, inbred c57bl, mice, inbred DBA, mice, knockout, time factors.

Sanchez Fauquier, A., M. Guillen, J. Martin, A.P. Kendal, and J.A. Melero (1991). Conservation of epitopes recognized by monoclonal antibodies against the separated subunits of influenza hemagglutinin among type A viruses of the same and different subtypes. Archives of Virology 116(1-4): 285-92.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Monoclonal antibodies raised against the separated hemagglutinin subunits (HA1 and HA2) of influenza A/Vic/3/75 (H3N2) virus were tested against a large panel of human and avian strains. The epitopes recognized by most antibodies were conserved among subtype H3 viruses, but reactivity of some antibodies with members of other subtypes was also observed. Particularly, the H4 virus reacted with most antibodies directed against the HA2 subunit. These results are discussed in terms of sequence similarities between subtypes and application of these antibodies as subtyping reagents.

            Descriptors:  antibodies, viral immunology, epitopes immunology, hemagglutinins viral immunology, influenza A virus immunology, antibodies, monoclonal immunology, cross reactions immunology, electrophoresis, polyacrylamide gel, hemagglutinin glycoproteins, influenza virus, avian classification, avian immunology, human classification, human immunology, influenza A virus classification.

Sander Wewer, M., R. Schauer, and A.P. Corfield (1982). Substrate specificity of viral, bacterial and mammalian sialidases with regard to different N,O-acetylated sialic acids and GM1. Advances in Experimental Medicine and Biology 152: 215-22.  ISSN: 0065-2598.

            NAL Call Number:  448.3 AC85

            Descriptors:  bacteria enzymology, gm1 ganglioside metabolism, gangliosides metabolism, influenza A virus avian enzymology, neuraminidase metabolism, paramyxoviridae enzymology, sialic acids metabolism, acetylation, species specificity, substrate specificity, time factors.

Sanger, C., E. Muhlberger, H.D. Klenk, and S. Becker (2001). Adverse effects of MVA-T7 on the transport of Marburg virus glycoprotein. Journal of Virological Methods 91(1): 29-35.  ISSN: 0166-0934.

            NAL Call Number:  QR355.J6

            Abstract:  Expression of glycoproteins has been carried out successfully using recombinant vaccinia virus vectors. Especially attractive is the use of recombinant vaccinia viruses which express the DNA-dependent RNA polymerase of the phage T7 (T7-polymerase). The T7-polynerase drives the transcription of plasmid-based genes under the control of the T7 RNA polymerase promoter transfected into the infected cell. Comparison of two different recombinant vaccinia viruses, vTF7-3 and MVA-T7, revealed that post-translational processing of Marburg virus surface glycoprotein (GP) is impaired in the MVA-T7 but not in the vTF7-3 system. Influenza virus hemagglutinin, however, was transported and processed like the authentic protein in both systems. It is shown that transport of GP in the MVA-T7 system is not completely blocked, but the vast majority of molecules remained Endo H-sensitive. Only trace amounts evaded the endoplasmatic reticulum and reached the plasma membrane. Thus, the adverse effects of MVA-T7 on the processing of recombinant glycoproteins cannot be predicted, and correct processing has to be investigated for every expressed glycoprotein.

            Descriptors:  genetic vectors, vaccinia virus genetics, viral envelope proteins metabolism, cell membrane metabolism, endoplasmic reticulum metabolism, HeLa cells, hemagglutinins viral genetics, hemagglutinins viral metabolism, influenza A virus avian genetics, avian metabolism, protein processing, post translational, protein transport, viral envelope proteins genetics.

Sansom, M.S. and I.D. Kerr (1993). Influenza virus M2 protein: a molecular modelling study of the ion channel. Protein Engineering 6(1): 65-74.  ISSN: 0269-2139.

            NAL Call Number:  TP248.P77P763

            Abstract:  The influenza A M2 protein forms cation-selective ion channels which are blocked by the anti-influenza drug amantadine. A molecular model of the M2 channel is presented in which a bundle of four parallel M2 transbilayer helices surrounds a central ion-permeable pore. Analysis of helix amphipathicity was used to aid determination of the orientation of the helices about their long axes. The helices are tilted such that the N-terminal mouth of the pore is wider than the C-terminal mouth. The channel is lined by residues V27, S31 and I42. Residues D24 and D44 are located at opposite mouths of the pore, which is narrowest in the vicinity of I42. Energy profiles for interaction of the channel with Na+, amantadine-H+ and cyclopentylamine-H+ are evaluated. The interaction profile for Na+ exhibits three minima, one at each mouth of the pore, and one in the region of residue S31. The amantadine-H+ profile exhibits a minimum close to S31 and a barrier near residue I42. This provides a molecular model for amantadine-H+ block of M2 channels. The profile for cyclopentylamine-H+ does not exhibit such a barrier. It is predicted that cyclopentylamine-H+ will not act as an M2 channel blocker.

            Descriptors:  influenza A virus avian chemistry, ion channels chemistry, protein structure, tertiary, viral matrix proteins chemistry, amantadine chemistry, amantadine metabolism, computer simulation, cyclopentanes chemistry, cyclopentanes metabolism, ion channels metabolism, models, molecular, protein structure, secondary, protons, receptors, nicotinic chemistry, receptors, nicotinic metabolism, sodium chemistry, sodium metabolism, viral matrix proteins metabolism.

Sauter, C., U. Baumberger, S. Ekenbark, and J. Lindenmann (1973). Replication of an avian myxovirus in primary cultures of human leukemic cells. Cancer Research 33(11): 3002-7.  ISSN: 0008-5472.

            NAL Call Number:  448.8 C16

            Descriptors:  influenza A virus avian, leukemia microbiology, virus replication, cultured cells, leukemia, lymphocytic, leukemia, myelocytic, acute, leukemia, myeloid, virus cultivation.

Sauter, C., M. Ellison, and J. Lindenmann (1978). Association of carcinoembryonic antigen (CEA) and influenza antigen. European Journal of Cancer 14(6): 623-8.  ISSN: 0014-2964.

            Descriptors:  carcinoembryonic antigen, hemagglutinins viral, influenza A virus avian immunology, bronchial neoplasms immunology, cell line, cell membrane immunology, virus replication.

Schafer, J., M.L. Khristova, T.L. Busse, R. Sinnecker, I.G. Kharitonenkov, C. Schrader, J. Suss, and D. Bucher (1992). Analysis of internal proteins of influenza A (H2N2) viruses isolated from birds in East Germany in 1983. Acta Virologica 36(2): 113-20.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Proteins and RNAs of influenza A (H2N2) viruses isolated from birds in 1983 in East Germany were compared antigenically with those of H2N2 human strains. The electrophoretic mobility of the viral proteins and of the S1-treated double-stranded RNAs from two human and six avian strains, as well as the results of EIA-tests using monoclonal antibodies to their matrix protein and nucleoproteins indicate an antigenic relationship between the avian isolates and human strains of H2N2 subtype. One of the avian strains had a reduced amount of matrix protein.

            Descriptors:  antigens, viral analysis, epitopes analysis, influenza A virus avian chemistry, human chemistry, RNA viral analysis, viral matrix proteins analysis, antibodies, monoclonal, ducks, enzyme linked immunosorbent assay, East Germany.

Schefer, J., M.L. Khristova, T.L. Busse, R. Sinnecker, and I.G. Kharitonenkov (1990). Standartizatsiia uslovii vyiavleniia vnutrennikh belkov virusa grippa pri issledovanii ikh antigennykh svoistv v tverdofaznom immunofermentnom analize. [Standardization of conditions for detecting the internal proteins of the influenza virus in studying their antigenic properties in solid-phase immunoenzyme analysis]. Voprosy Virusologii  35(2): 105-8.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The influence of the conditions of adsorption and virion destruction by freezing-thawing and detergents on the detection of M1 and NP proteins of different influenza virus strains by solid-phase enzyme immunoassay with direct virion adsorption on polystyrene was studied. It was found that for the detection of M1 protein the optimal conditions included virion disruption with detergent and adsorption to polystyrene at 4 degrees C, and for NP protein disruption by freezing-thawing at adsorption to polystyrene at 37 degrees C. In the study of the antigenic properties of protein M1 of different influenza virus strains using monoclonal antibodies it was shown to be necessary, first, to achieve maximum detection of proteins and, second, to standardize the amount of the adsorbed antigen with polyclonal antibodies.

            Descriptors:  antigens, viral analysis, capsid analysis, influenza A virus avian analysis, human analysis, viral core proteins analysis, viral matrix proteins analysis, adsorption, antibodies, monoclonal diagnostic use, antigens, viral immunology, capsid immunology, enzyme linked immunosorbent assay methods, enzyme linked immunosorbent assay standards, avian immunology, human immunology, temperature, viral core proteins immunology, viral matrix proteins immunology, virion analysis, virion immunology.

Scheiffele, P., A. Rietveld, T. Wilk, and K. Simons (1999). Influenza viruses select ordered lipid domains during budding from the plasma membrane. Journal of Biological Chemistry 274(4): 2038-44.  ISSN: 0021-9258.

            NAL Call Number:  381 J824

            Abstract:  During the budding of enveloped viruses from the plasma membrane, the lipids are not randomly incorporated into the envelope, but virions seem to have a lipid composition different from the host membrane. Here, we have analyzed lipid assemblies in three different viruses: fowl plague virus (FPV) from the influenza virus family, vesicular stomatitis virus (VSV), and Semliki Forest virus (SFV). Analysis of detergent extractability of proteins, cholesterol, phosphoglycerolipids, and sphingomyelin in virions showed that FPV contains high amounts of detergent-insoluble complexes, whereas such complexes are largely absent from VSV or SFV. Cholesterol depletion from the viral envelope by methyl-beta-cyclodextrin results in increased solubility of sphingomyelin and of the glycoproteins in the FPV envelope. This biochemical behavior suggests that so-called raft-lipid domains are selectively incorporated into the influenza virus envelope. The "fluidity" of the FPV envelope, as measured by the fluorescence polarization of diphenylhexatriene, was significantly lower than compared with VSV or SFV. Furthermore, influenza virus hemagglutinin incorporated into the envelope of recombinant VSV was largely detergent-soluble, indicating the depletion of raft-lipid assemblies from this membrane. The results provide a model for lipid selectivity during virus budding and support the view of lipid rafts as cholesterol-dependent, ordered domains in biological membranes.

            Descriptors:  influenza A virus avian physiology, membrane lipids metabolism, Semliki Forest virus physiology, vesicular stomatitis Indiana virus physiology, cell line, cell membrane virology, detergents, fluorescence polarization, hamsters, solubility.

Schettler, C.H. (1972). Immunologische Studien mit Tween-Ather Spaltprodukten von drei serologisch verschiedenen aviaren Influeza A Viren. [Immunological studies with Tween-ether fission products of three serologically different avian influenza A viruses]. Tierarztliche Umschau 27(10): 494-496.  ISSN: 0049-3864.

            NAL Call Number:  41.8 T445

            Descriptors:  avian influenza, strains, vaccines, immunology, ducks.

Schild, G.C., R.W. Newman, R.G. Webster, D. Major, and V.S. Hinshaw (1980). Antigenic analysis of influenza A virus surface antigens: considerations for the nomenclature of influenza virus. Brief review. Archives of Virology 63(3-4): 171-84.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Descriptors:  antigens, surface analysis, antigens, viral analysis, hemagglutinins viral analysis, influenza A virus immunology, antigens, viral classification, hemagglutinins viral classification, influenza A virus avian immunology, human immunology, porcine immunology, neuraminidase immunology, terminology.

Schild, G.C., R.W. Newman, R.G. Webster, D. Major, and V.S. Hinshaw (1980). Antigenic analysis of influenza A virus surface antigens: considerations for the nomenclature of influenza virus. Comparative Immunology, Microbiology and Infectious Diseases 3(1-2): 5-18.  ISSN: 0147-9571.

            NAL Call Number:  QR180.C62

            Descriptors:  antigens, viral analysis, influenza A virus avian immunology, human immunology, influenza A virus immunology, hemagglutinins viral analysis, horses, porcine immunology, influenza A virus classification, neuraminidase immunology, serotyping, terminology.

Schild, G.C. and H.G. Pereira (1969). Characterization of the ribonucleoprotein and neuraminidase of influenza A viruses by immunodiffusion. Journal of General Virology 4(3): 355-63.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  neuraminidase analysis, orthomyxoviridae analysis, RNA viral analysis, antigens analysis, bile acids and salts pharmacology, complement fixation tests, detergents pharmacology, hemagglutinins viral analysis, immunochemistry, immunodiffusion, immunoelectrophoresis, influenza A virus avian analysis, neuraminidase antagonists and inhibitors, orthomyxoviridae drug effects.

Schlesinger, R.W., P.J. Husak, G.L. Bradshaw, and P.P. Panayotov (1998 ). Mechanisms involved in natural and experimental neuropathogenicity of influenza viruses: evidence and speculation. Advances in Virus Research 50: 289-379.  ISSN: 0065-3527.

            NAL Call Number:  448.3 AC85

            Descriptors:  central nervous system diseases virology, influenza A virus avian pathogenicity, human pathogenicity, influenza B virus pathogenicity, peripheral nervous system diseases virology, central nervous system diseases pathology, peripheral nervous system diseases pathology.

Schmidt, M.F. (1982). Acylation of viral spike glycoproteins: a feature of enveloped RNA viruses. Virology 116(1): 327-38.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  fatty acids metabolism, glycoproteins metabolism, RNA viruses metabolism, viral proteins metabolism, acylation, alphavirus metabolism, hemagglutinins viral, influenza A virus avian metabolism, human metabolism, murine hepatitis virus metabolism, Newcastle disease virus metabolism.

Schmidt, M.F., R.T. Schwarz, and H. Ludwig (1976). Fluorosugars inhibit biological properties of different enveloped viruses. Journal of Virology 18(3): 819-23.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Both 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose were found to be potent inhibitors of the synthesis of infectious Semliki forest and fowl plague virus in chicken embryo cells and also of pseudorabies virus grown in rabbit kidney cells. It was found that the pseudorabies virus-mediated cell fusion and the synthesis of functional hemagglutinin of fowl plague virus were blocked. In all cases the 2-deoxy-2-fluoro-D-mannose-caused inhibition was stronger than the 2-deoxy-2-fluoro-D-glucose- or 2-deoxy-D-glucose-mediated blocks. Studies on the virus-specified proteins from Semiliki forest virus-infected cells grown in the presence of the inhibitors show that the target of the fluorosugar action, parallel to the well-studied effects of 2-deoxy-D-glucose, is the glycoprotein biosynthesis.

            Descriptors:  deoxy sugars analogs and derivatives, deoxyglucose analogs and derivatives, herpesviridae drug effects, herpesvirus 1, suid drug effects, influenza A virus avian drug effects, rhamnose analogs and derivatives, Semliki Forest virus drug effects, cell fusion drug effects, cell line, deoxyglucose pharmacology, fluorine, glycoproteins biosynthesis, hemagglutinins viral, herpesvirus 1, suid growth and development, herpesvirus 1, suid metabolism, avian growth and development, avian metabolism, rhamnose pharmacology, Semliki Forest virus growth and development, Semliki Forest virus metabolism, viral proteins biosynthesis, virus replication drug effects.

Schmidt, R.C., H.F. Maassab, and F.M. Davenport (1974). Infection by influenza A viruses of tracheal organ cultures derived from homologous and heterologous hosts. Journal of Infectious Diseases 129(1): 28-36.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  influenza A virus, tracheal tissue culture, pathogenesis, human, swine, equine, chicken, ferret.

Schofield, D.J., J.R. Stephenson, and N.J. Dimmock (1997). High and low efficiency neutralization epitopes on the haemagglutinin of type A influenza virus. Journal of General Virology 78(Pt. 10): 2441-6.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  The relationship between the efficiency of the neutralization process and the affinity of five monoclonal IgG antibodies specific for the haemagglutinin of type A influenza virus has been investigated by determining their neutralization rate constants (Kneut.) and affinities (Kdissoc.). We addressed the hypothesis that if antibody affinity alone determined the efficiency of neutralization, then the Kneut.:Kdissoc. ratio would be the same for all antibodies. However, we found that the Kneut.:Kdissoc. ratio varied by up to 125-fold, suggesting that properties unique to the epitope are of major importance in determining the efficiency of neutralization. These data suggest that vaccines should preferentially stimulate antibodies to epitopes that mediate the most efficient neutralization, and that a high Kdissoc. should be an important but secondary consideration.

            Descriptors:  antibodies, viral immunology, antigens, viral immunology, hemagglutinin glycoproteins, influenza virus immunology, influenza A virus avian immunology, antibodies, monoclonal immunology, antibody affinity, antigen antibody reactions, chickens, epitope mapping, kinetics, neutralization tests.

Schofield, D.J., J.R. Stephenson, and N.J. Dimmock (1997). Variations in the neutralizing and haemagglutination-inhibiting activities of five influenza A virus-specific IgGs and their antibody fragments. Journal of General Virology 78(Pt. 10):  2431-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Neutralization and haemagglutination-inhibition (HI) of a type A influenza virus by a panel of five monoclonal IgGs, their F(ab')2s, Fabs and Fabs+ anti-mouse Fab were compared. The MAbs were specific for antigenic sites A, B and D of the haemagglutinin. Activities of the IgGs varied by up to 6-fold on a molar basis, apart from the HI activity of HC58 which was > 100-fold lower. This was not due to low functional affinity as HC58 had the second highest value (nM) as determined by an equilibrium method with whole virions. Conversion to the F(ab')2 reduced neutralization and HI by only 2- to 6-fold, indicating that the Fc region had little involvement in these processes. However, all Fabs had low neutralization and HI activity compared with their IgGs, neutralization being reduced by 86 to > 1912-fold, and HI by 13 to > 69-fold. Although decreased, their affinities remained high, in the nM range. Neutralization and HI by three of the Fabs (HC2, HC3W and HC61) were restored by the addition of anti-Fab IgG; however, HC10 Fab+anti-Fab IgG still had no detectable neutralization activity but gave HI, and HC58 Fab+anti-Fab IgG had no detectable HI activity but neutralized to the same extent as its IgG. The different properties of the antibodies are discussed in the light of their known mechanisms of action: HI by steric blocking of attachment of virus to the red cell receptor, and neutralization by the inhibition of post-attachment events (HC2, HC10 and HC61). The data demonstrate just how variable are the antiviral properties of individual IgGs.

            Descriptors:  antibodies, monoclonal immunology, antibodies, viral immunology, hemagglutinin glycoproteins, influenza virus immunology, influenza A virus avian immunology, adult, antibodies, anti idiotypic immunology, antigen antibody reactions, cell membrane immunology, chickens, dose response relationship, immunologic, hemagglutination inhibition tests, immunoglobulin g immunology, immunoglobulins, Fab immunology, membrane glycoproteins immunology, neutralization tests.

Scholtissek, C. (1979). The genes coding for the surface glycoproteins of influenza A viruses contain a small conserved and a large variable region. Virology 93(2): 594-7.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes, structural, genes viral, glycoproteins genetics, influenza A virus genetics, viral proteins genetics, base sequence, hemagglutinins viral genetics, influenza A virus avian genetics, neuraminidase genetics, nucleic acid hybridization, RNA viral genetics.

Scholtissek, C. (1976). Inhibition of influenza RNA synthesis by virazole (ribavirin). Archives of Virology 50(4): 349-52.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Virazole (ribavirin) inhibits the RNA synthesis of an influenza A virus (fowl plague). Neither virion RNA nor complementary RNA are produced. Although the effect of virazole can be counteracted by guanosine the inhibitor does not interfere with the uptake or incorporation of labelled guanosine into chick embryo cells, nor does replacement of glucose by mannose amplify the effect of virazole. Thus virazole seems not to act via an interference with the GTP pool. Synthesis of Semliki Forest virus RNA is not affected by virazole.

            Descriptors:  influenza A virus avian metabolism, RNA viral biosynthesis, ribavirin pharmacology, ribonucleosides pharmacology, DNA directed RNA polymerases biosynthesis, depression, chemical, hemagglutinins viral, avian drug effects, neuraminidase biosynthesis, Semliki Forest virus metabolism, tissue culture, viral proteins biosynthesis.

Scholtissek, C. (1985). Stability of infectious influenza A viruses at low pH and at elevated temperature. Vaccine 3(3 Suppl.): 215-8.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  After treatment of different strains of influenza A at low pH, the threshold pH, at which the infectivity was lost, depended on the haemagglutinin (HA) subtype of the virus strain. Strains with noncleaved HA were much more stable when compared to strains with cleaved HA. These observations might explain why duck influenza viruses spread well by lake water, while highly pathogenic strains with cleaved HA do not. There were also significant differences in heat stability of infectivity among influenza A strains, which do not correlate with differences in stability at low pH.

            Descriptors:  influenza A virus pathogenicity, chick embryo, heat, hemagglutinins viral, hydrogen-ion concentration, influenza A virus avian pathogenicity, human pathogenicity, species specificity.

Scholtissek, C. (1985). Stability of infectious influenza A viruses to treatment at low pH and heating. Archives of Virology 85(1-2): 1-11.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  We have measured the infectivity of influenza A virus strains grown either in embryonated eggs or in chick embryo cells in culture after treatment at low pH. At pH values at which hemolysis occurs there was an irreversible loss of infectivity. The threshold pH, at which the infectivity was lost, depended on the hemagglutinin subtype of the virus strain. All H5 and H7 strains tested were extremely labile at low pH. In contrast, all H3 strains were relatively stable, independent of the species from which the viruses were isolated. With several H1 viruses the hemagglutination (HA) activity was irreversibly lost at intermediate pH values causing inactivation of infectivity. Strains with noncleaved hemagglutinins were much more stable. These observations might explain why duck influenza viruses can easily survive in lake water and wet faeces, and multiply in the intestinal tract, where trypsin is present. There are also significant differences in heat stability exhibited by influenza A strains. In contrast to pH stability this is not a specific trait of the hemagglutinin, since it can be influenced by reassortment. There is no correlation between the stability of infectivity at low pH and heat.

            Descriptors:  heat, influenza A virus pathogenicity, cultured cells, chick embryo, hemagglutination, viral, hydrogen-ion concentration, influenza A virus avian growth and development, influenza A virus classification, influenza A virus growth and development.

Scholtissek, C., H. Becht, and R. Drzeniek (1967). Biochemical studies on the cytopathic effect of influenza viruses. Journal of General Virology 1(2): 219-25.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  antiviral agents pharmacology, cytopathogenic effect, viral, influenza A virus avian drug effects, avian pathogenicity, carbon isotopes, ethylenes pharmacology, imines pharmacology, leucine metabolism, quinones pharmacology, RNA viral metabolism, tritium, uridine metabolism, virus cultivation.

Scholtissek, C., H. Becht, and I. Macpherson (1970). The effect of mithramycin on the multiplication of myxoviruses. Journal of General Virology 8(1): 11-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  antibiotics, antineoplastic pharmacology, influenza A virus avian drug effects, Newcastle disease virus drug effects, virus inhibitors, virus replication drug effects, antigens metabolism, chick embryo, dactinomycin pharmacology, fibroblasts, hemagglutination inhibition tests, hemagglutination tests, avian enzymology, avian growth and development, avian immunology, avian metabolism, leucine metabolism, neuraminidase metabolism, Newcastle disease virus growth and development, proteins biosynthesis, RNA biosynthesis, RNA nucleotidyltransferases metabolism, RNA viral biosynthesis, tritium, uridine metabolism.

Scholtissek, C., H. Burger, P.A. Bachmann, and C. Hannoun (1983). Genetic relatedness of hemagglutinins of the H1 subtype of influenza A viruses isolated from swine and birds. Virology 129(2): 521-3.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The hemagglutinin (HA) gene of the influenza virus subtype H1N1 isolated from pigs and birds has been analyzed by the hybridization technique. According to the RNase protection data the HA genes of recent isolates from pigs in Northern Europe are genetically more closely related to those of isolates from birds in Europe and North America than to those of isolates from pigs in the United States, Taiwan, and Italy. Thus, two different H1N1 subtypes are circulating in the pig population. The results are consistent with the view that H1N1 viruses can be transmitted from birds to pigs and/or vice versa.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, porcine genetics, genetics, birds microbiology, genes viral, avian immunology, avian isolation and purification, porcine classification, porcine immunology, porcine isolation and purification, nucleic acid hybridization, swine microbiology.

Scholtissek, C., H. Burger, O. Kistner, and K.F. Shortridge (1985). The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses. Virology 147(2): 287-94.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  In an attempt to assess the importance of the nucleoprotein (NP) in the determination of host specificity, a series of experiments was performed on influenza A viruses of the H3N2 subtype. We have examined rescue of mutants of A/FPV/Rostock/34 with temperature-sensitive (ts) lesions in the nucleoprotein (NP) gene by double infection of chick embryo cells with H3N2 strains isolated from different species. The ts mutants could be rescued by all avian H3N2 strains but not by any of the human H3N2 isolates. Only two of the swine H3N2 strains tested were able to rescue our mutants. The NP gene of these two swine isolates resembled the NP gene of the avian strains genetically in the hybridization test. However, their NPs reacted differently with a set of monoclonal antibodies when compared with NPs of avian H3N2 strains. Concerning multiplication in ducks they behaved like the other swine and human strains. The phosphopeptide fingerprints of all swine isolates tested were alike and were different from those of human or avian origin. Our observations are compatible with the idea that human H3N2 strains might not be able to cross the species barrier to birds directly, and possibly also not the other way around, without prior reassortment in pigs, which seem to have a broader host range concerning the compatibility of the NP gene in reassortants.

            Descriptors:  capsid physiology, influenza A virus avian physiology, human physiology, porcine physiology, influenza A virus physiology, viral core proteins physiology, antibodies, viral analysis, capsid analysis, capsid genetics, capsid immunology, cultured cells, chick embryo, ducks, electrophoresis, polyacrylamide gel, epitopes, fowl plague immunology, fowl plague microbiology, avian genetics, avian immunology, human genetics, human immunology, porcine genetics, porcine immunology, mutation, nucleic acid hybridization, phosphopeptides analysis, recombination, genetic, temperature, viral core proteins analysis, viral core proteins genetics, viral core proteins immunology.

Scholtissek, C. and J. Damgen (1974). Proceedings: Specific inhibition of influenza and Semliki Forest virus RNA synthesis by glucosamine. Hoppe Seyler's Zeitschrift Fur Physiologische Chemie 355(10): 1252-3.  ISSN: 0018-4888.

            NAL Call Number:  384 Z38

            Descriptors:  glucosamine pharmacology, influenza A virus avian metabolism, RNA viral biosynthesis, Semliki Forest virus metabolism, chick embryo, depression, chemical.

Scholtissek, C. and G.P. Faulkner (1979). Amantadine-resistant and -sensitive influenza A strains and recombinants. Journal of General Virology 44(3): 807-15.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Several influenza A strains and recombinants of fowl plague virus (FPV) with a known gene constellation were tested for amantadine sensitivity under two different experimental conditions. In a haemagglutinin yield analysis of a single growth cycle experiment FPV was found to be highly sensitive to amantadine, while in the plaque reduction and inhibition test it was highly resistant. With the A3 Hong Kong and equi 2 strains the opposite observation was made. The A2 Singapore strain was sensitive while Ao PR8 was resistant in both tests. In the haemagglutinin yield analysis of a single growth cycle all recombinants carrying segment 4 (HA) of the resistant strain were resistent against amantadine, independent of the derivation of the other genes. In the plaque reduction and inhibition test recombinants carrying the haemagglutinin of the sensitive strain were either resistant or sensitive depending on the gene constellation. Drug sensitivity was transferred by the combination of segments 5 (NP) and 6 (NA). Segment 7 (M) of certain sensitive strains seems to counteract this effect. The results are compatible with the concept that amantadine resistance or sensitivity is not confined to a single gene product or a single mechanism.

            Descriptors:  amantadine pharmacology, influenza A virus drug effects, recombination, genetic, drug resistance, microbial, hemagglutinins viral analysis, influenza A virus avian drug effects, human drug effects, influenza A virus genetics, influenza A virus immunology, mutation, plaque assay.

Scholtissek, C., E. Harms, W. Rohde, M. Orlich, and R. Rott (1976). Correlation between RNA fragments of fowl plague virus and their corresponding gene functions. Virology 74(2): 332-44.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes, influenza A virus avian metabolism, RNA viral metabolism, base sequence, nucleic acid denaturation, nucleic acid hybridization, plaque assay, recombination, genetic.

Scholtissek, C., G. Kaluza, and R. Rott (1972). Stability and precursor relationships of virus RNA. Journal of General Virology 17(2): 213-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian metabolism, Newcastle disease virus metabolism, protein precursors, RNA viral metabolism, Semliki Forest virus metabolism, base sequence, centrifugation, density gradient, chick embryo, culture media, dactinomycin pharmacology, fibroblasts, glucosamine pharmacology, hemagglutination tests, avian growth and development, Newcastle disease virus growth and development, nucleic acid hybridization, plaque assay, RNA biosynthesis, viral biosynthesis, Semliki Forest virus growth and development, tissue culture, tritium, uracil nucleotides metabolism, uridine metabolism, virus replication.

Scholtissek, C., I. Koennecke, and R. Rott (1978). Host range recombinants of fowl plague (influenza A) virus. Virology 91(1): 79-85.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian genetics, recombination, genetic, cell line, chickens microbiology, genes viral, hemagglutinins viral analysis, avian growth and development, avian pathogenicity, human genetics, influenza A virus genetics, RNA viral biosynthesis.

Scholtissek, C., R. Kruczinna, R. Rott, and H.D. Klenk (1974). Characteristics of an influenza mutant temperature-sensitive for viral RNA synthesis. Virology 58(2): 317-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, mutation, RNA viral biosynthesis, temperature, amino acids metabolism, antigens, viral analysis, chick embryo, DNA directed RNA polymerases metabolism, electrophoresis, polyacrylamide gel, fibroblasts, fluorouracil, hemagglutinins viral analysis, avian enzymology, avian growth and development, avian immunology, mutagens, neuraminidase analysis, peptide synthesis, tissue culture, tritium,  uridine metabolism, viral proteins biosynthesis, virus replication.

Scholtissek, C., S. Ludwig, and W.M. Fitch (1993). Analysis of influenza A virus nucleoproteins for the assessment of molecular genetic mechanisms leading to new phylogenetic virus lineages. Archives of Virology 131(3-4): 237-50.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The nucleoprotein (NP) gene of influenza A viruses is decisive for separating two large individually evolving reservoirs in birds and humans. A phylogenetic analysis of the NP gene revealed that all mammalian influenza viruses originated--directly or indirectly--from an avian ancestor. The stable introduction of an avian influenza A virus into a mammalian species seems to be a relatively rare event, the latest one occurred in 1979 when such an avian virus was introduced into pigs in Northern Europe which gave rise to a new lineage. At least two concomitant events are required for such a new and stable introduction: (1) The new species has to become infected, and (2) a mutation in the polymerase complex has to establish a labile variant, which is prone to provide a large number of different variants, from which some can adapt rapidly to the new host (or to any unusual environments). Since such mutator mutations might be advantageous only during stress periods, variants with a less error prone polymerase might emerge again after adaptation. Examples for such fluctuations in terms of mutational and evolutionary rates are discussed in this brief review.

            Descriptors:  influenza A virus genetics, nucleoproteins chemistry, phylogeny, viral core proteins chemistry, genes viral, influenza A virus chemistry, mutation, nucleoproteins genetics, sequence homology, amino acid, viral core proteins genetics.

Scholtissek, C. and K. Muller (1988). Effect of dimethylsulfoxide (DMSO) on virus replication and maturation. Archives of Virology 100(1-2): 27-35.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  At intermediate concentrations of DMSO the yields of infectious virus and biologically active hemagglutinin and neuraminidase of an influenza A virus (fowl plague virus) and of reassortants therefrom are enhanced severalfold, even though viral protein synthesis is not significantly affected. A corresponding enhancing effect was also found with New castle disease and Semliki Forest viruses. At elevated concentrations of DMSO virus yield decreases, and under these conditions the synthesis of the late influenza virus proteins is specifically inhibited. The results indicate that DMSO can facilitate the assembly of virus particles, and viral components, which are normally produced in surplus amounts, now contribute to the maturation of infectious particles.

            Descriptors:  dimethyl sulfoxide pharmacology, virus replication drug effects, hemagglutination, viral drug effects, influenza A virus avian drug effects, avian growth and development, Newcastle disease virus drug effects, Newcastle disease virus growth and development, plaque assay, Semliki Forest virus drug effects, Semliki Forest virus growth and development, viral proteins biosynthesis, virus cultivation.

Scholtissek, C. and K. Muller (1991). Failure to obtain drug-resistant variants of influenza virus after treatment with inhibiting doses of 3-deazaadenosine and H7. Archives of Virology 119(1-2): 111-8.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  3-Deazaadenosine and H7 specifically inhibit influenza virus replication under conditions at which they have no effect on other tested RNA viruses. This effect can be significantly potentiated by concomitant application of both compounds. Even under the most stringent conditions we failed to obtain any drug resistant variants. A possible explanation for this failure is that these compounds presumably do not act on a viral component like amantadine which was used as a control, but they interfere with cellular enzymes (factors) absolutely essential for influenza virus replication but more or less dispensable for the survival of the cell.

            Descriptors:  influenza A virus avian drug effects, isoquinolines pharmacology, piperazines pharmacology, tubercidin pharmacology, 1 5 isoquinolinesulfonyl 2 methylpiperazine, cultured cells, chick embryo, drug combinations, drug resistance, microbial, virus replication drug effects.

Scholtissek, C. and K. Muller (1988). Interference between influenza A viruses with a cleavable and a noncleavable hemagglutinin; pH-stability after mixed infection. Archives of Virology 101(1-2): 119-23.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The infectivity of influenza A viruses like fowl plague virus (FPV) with a cleaved hemagglutinin (HA) is highly sensitive to treatment at pH 5, while strains like PR 8 or virus N with a noncleaved HA survive under this condition. After double infection of chick embryo cells with FPV and PR 8 or virus N, the yield of virus with the HA gene of FPV is greatly reduced. However, it can now survive treatment at pH 5, and the surviving FPV particles form plaques only in the presence of trypsin, indicating that they were coated by the HA of PR 8 or virus N, depending on the coinfecting virus. The results are discussed with respect to the build-up and maintenance of a large reservoir of nonpathogenic influenza A viruses with noncleavable HA in water fowl.

            Descriptors:  fowl plague microbiology, hemagglutinins viral physiology, influenza A virus avian pathogenicity, cultured cells, fibroblasts microbiology, fowl plague enzymology, hemagglutinins viral metabolism, hydrogen-ion concentration, avian enzymology, plaque assay, trypsin physiology, viral interference, water microbiology.

Scholtissek, C. and K. Muller (1983). Temperature-sensitive mutants of fowl plague virus (influenza A) generated by undiluted passages at 33 degrees C. Journal of General Virology 64(Pt. 12): 2621-9.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Temperature-sensitive (ts) mutants obtained by undiluted passages of fowl plague virus at 33 degrees C have their defects located mainly in RNA segments 3, 4 and 8 as determined by rescue to wild-type with standard ts mutants. This result is different from that obtained after treatment of virus with mutagens, where the frequency of mutations follows roughly the target size of the RNA segments. Many isolates generated after undiluted passages at 33 degrees C, which seem to have mutations in RNA segments 3 and 4, can be rescued to wild-type. This occurs, however, with certain defined standard ts mutants having a defect in RNA segment 4, but not by other segment 4 mutants. One such mutant, ts 1/93 (ts defect in segment 3), interferes with the multiplication of ts 227 (ts defect in segment 4) at the permissive temperature, presumably at the level of vRNA synthesis, preventing reassortment to wild-type. Similarly, ts 263 (ts defect in segment 3) interferes with the multiplication of ts 1/1 (ts defect in segment 4). For other such interfering mutants, the mechanism preventing reassortment to wild-type is different from that of ts 1/93 or ts 1/1, but is not yet understood. Thus, the number of mutations as determined by rescue with standard ts mutants in isolates obtained by undiluted passages is overestimated due to intrinsic interference.

            Descriptors:  genes viral, influenza A virus avian genetics, cultured cells, chick embryo, fluorouracil pharmacology, avian growth and development, mutation, plaque assay, RNA viral genetics, temperature, viral interference.

Scholtissek, C., K. Muller, and S. Herzog (1986). Influence of insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) on influenza virus multiplication. Virus Research 6(3): 287-94.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) interfere with the multiplication of fowl plague virus, an influenza A virus, in primary chick embryo cells. Specifically the production of the viral glycoproteins hemagglutinin and neuraminidase are affected by the drugs. A decrease or omission of glucose from the culture medium enhances this effect, which is in agreement with the idea that these drugs act on virus replication via a shortage of glucose in the host cell. Virus replication in cells of different organs is affected to different extents by insulin and TPA.

            Descriptors:  glucose metabolism, influenza A virus avian drug effects, insulin pharmacology, tetradecanoylphorbol acetate pharmacology, virus replication drug effects, cell line, cultured cells, chick embryo, electrophoresis, polyacrylamide gel, avian physiology.

Scholtissek, C. and B.R. Murphy (1978). Host range mutants of an influenza A virus. Archives of Virology 58(4): 323-33.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Temperature-sensitive (ts) mutants of fowl plague virus with a ts-lesion in segment 1 (ts 3, polymerase 1 gene) or segment 2 (ts 90, transport gene) do not form plaques on MDCK cells at the permissive temperature, while the wild type and ts-mutants of other groups are able to do so. This property is correlated with the ts-lesion, since revertants for the ts-lesion of ts 3 and ts 90 again form plaques on MDCK cells. The block on MDCK cells--at least for ts3--may be located in a late function, since viral RNA polymerase and hemagglutinin are formed in almost normal yields. MDCK cells infected with ts 3 or ts 90 exhibit a retarded cytopathic effect at 33 degrees C, but no cytopathic effect at 39 degrees C, at which temperature the infected cells can be passaged and super-infected with the wild type strain. Cells surviving the infection with ts 90 at 33 degrees C sometimes grow out again to a normal monolayer. It is suggested that the spread of virus is inhibited under these conditions.

            Descriptors:  genes viral, influenza A virus avian growth and development, cell line, cytopathogenic effect, viral, DNA directed RNA polymerases biosynthesis, hemagglutinins viral, avian genetics, mutation, plaque assay, temperature.

Scholtissek, C., W. Rohde, E. Harms, and R. Rott (1977). Correlation between base sequence homology of RNA segment 4 and antigenicity of the hemagglutinin of influenza viruses. Virology 79(2): 330-6.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  base sequence, biochemistry, hemagglutinins viral analysis, influenza A virus analysis, influenza A virus immunology, RNA viral analysis, influenza A virus avian analysis, avian immunology, human analysis, human immunology, porcine analysis, porcine immunology, nucleic acid hybridization.

Scholtissek, C., W. Rohde, E. Harms, R. Rott, M. Orlich, and C.B. Boschek (1978). A possible partial heterozygote of an influenza A virus. Virology 89(2): 506-16.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, influenza A virus avian genetics, influenza A virus genetics, recombination, genetic, base sequence, heterozygote, avian analysis, influenza A virus analysis, mutation, neuraminidase analysis, nucleic acid conformation, RNA viral analysis.

Scholtissek, C. and R. Rott (1984). Correlation between loss of the temperature-sensitive phenotype and pathogenicity of fowl plague virus mutants in the chicken. Virus Research 1(2): 117-31.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The reversion of temperature-sensitive (ts) mutants of fowl plague virus to the ts+ phenotype was correlated with pathogenicity for chicken. Two types of ts mutants were investigated: those obtained by mutagenesis with 5-fluorouracil and those obtained by undiluted passages at 33 degrees C. The reversion frequency of the former mutants depended on the RNA segment in which the ts defect was located, mutations in RNA segments 1 and 2 having the highest reversion frequency, those in the RNA segments coding for the glycoproteins the lowest. ts mutants obtained by undiluted passages behaved differently in this respect. There was an approximate correlation between frequency of reversion and pathogenicity for chicken. Double mutants induced by 5-fluorouracil, having one tight and one leaky mutation, reverted easily without loss of the leaky mutation. These double mutants were still to a limited extent pathogenic for the chicken. Only one double mutant with two tight mutations (ts 293) was completely nonpathogenic after intramuscular inoculation. Two ts mutants with multiple tight defects (ts 1/1 and ts 3/18) obtained by undiluted passage did not revert to wild-type after injection into embryonated eggs and incubation at 33 degrees C, but they were still slightly pathogenic for the chicken. There was no obvious correlation between the shut-off temperature and pathogenicity of mutants carrying a single ts defect. However, for mutants with multiple tight mutations a high shut-off temperature seemed to be essential for reversion during serial passages as well as for pathogenicity in the chicken, when different routes of inoculation were examined. ts mutants seem to be safe as live vaccines only, (1) if they carry at least two tight ts defects, (2) if they have a relatively low shut-off temperature, and (3) if they could be administered other than via the respiratory tract.

            Descriptors:  influenza A virus avian genetics, mutation, temperature, chickens microbiology, fluorouracil pharmacology, avian pathogenicity.

Scholtissek, C. and R. Rott (1969). Effect of temperature on the multiplication of an Influenza virus. Journal of General Virology 5(2): 283-90.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian growth and development, fibroblasts, hemagglutination, viral, avian enzymology, leucine, neuraminidase metabolism, nucleosides, RNA nucleotidyltransferases metabolism, temperature, tissue culture, tritium.

Scholtissek, C. and R. Rott (1967). Failure of function of the "early protein" induced by an influenza virus in cells infected by Newcastle disease virus. Nature 213(72): 186.  ISSN: 0028-0836.

            NAL Call Number:  472 N21

            Descriptors:  dactinomycin pharmacology, influenza A virus avian, Newcastle disease virus, phenylalanine pharmacology, proteins, RNA viral biosynthesis, uridine metabolism, carbon isotopes, chick embryo.

Scholtissek, C. and R. Rott (1969). Ribonucleic acid nucleotidyl transferase induced in chick fibroblasts after infection with an influenza virus. Journal of General Virology 4(1): 125-37.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Descriptors:  influenza A virus avian, RNA nucleotidyltransferases, tissue culture, chickens, dactinomycin pharmacology, dextrans pharmacology, enzyme induction, fibroblasts, guanine nucleotides metabolism, magnesium pharmacology, nucleotides pharmacology, phenylalanine pharmacology, protamines pharmacology, RNA pharmacology, ribonucleases pharmacology, tritium.

Scholtissek, C. and R. Rott (1970). Synthesis in vivo of influenza virus plus and minus strand RNA and its preferential inhibition by antibiotics. Virology 40(4): 989-96.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cycloheximide pharmacology, dactinomycin pharmacology, influenza A virus avian metabolism, RNA viral biosynthesis, chickens, depression, chemical, fibroblasts, avian pathogenicity, phosphates metabolism, phosphorus isotopes, precipitation, RNA viral isolation and purification, tissue culture, tritium, uridine metabolism.

Scholtissek, C., R. Rott, and H.D. Klenk (1975). Two different mechanisms of the inhibition of the multiplication of enveloped viruses by glucosamine. Virology 63(1): 191-200.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  antiviral agents pharmacology, glucosamine pharmacology, influenza A virus avian drug effects, Newcastle disease virus drug effects, Semliki Forest virus drug effects, vesicular stomatitis Indiana virus drug effects, virus replication drug effects, culture media, cytidine pharmacology, DNA directed RNA polymerases metabolism, dose response relationship, drug, fructose metabolism, glucose metabolism, glycoproteins biosynthesis, guanosine pharmacology, avian growth and development, Newcastle disease virus growth and development, RNA viral biosynthesis, Semliki Forest virus growth and development, tritium, uracil nucleotides metabolism, uridine pharmacology, vesicular stomatitis Indiana virus growth and development, virus cultivation.

Scholtissek, C., R. Rott, D.K. Lvov, and I.A. Myasnikova (1980). Genetic relatedness of the neuramindase of influenza A strains Nav2, Nav3, and Nav6. Archives of Virology 65(3-4): 325-8.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  By molecular hybridization and by neuraminidase inhibition tests it is shown that all influenza A strains tested carrying an Nav3 or Nav2 neuraminidase (NA) are genetically highly related in their NA genes and cross-react serologically with specific antineuraminidase sera. The Nav6 strains exhibit a very low RNase protection after hybridization and do not cross-react serologically with Nav2 or Nav3 strains. Thus, the Nav2 and Nav3 strains comprise one group which is distinct from that of Nav6 strains.

            Descriptors:  genes viral, influenza A virus genetics, neuraminidase genetics, cross reactions, influenza A virus avian enzymology, avian genetics, influenza A virus enzymology, neuraminidase immunology, nucleic acid hybridization.

Scholtissek, C., R. Rott, M. Orlich, E. Harms, and W. Rohde (1977). Correlation of pathogenicity and gene constellation of an influenza A virus (fowl plague). I. Exchange of a single gene. Virology 81(1): 74-80.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes, influenza A virus avian pathogenicity, recombination, genetic, antibodies, viral biosynthesis, chickens, fluorouracil, avian analysis, avian immunology, influenza A virus pathogenicity, mutagens, mutation, RNA viral analysis.

Scholtissek, C., R.T. Schwarz, W. Keil, and H.D. Klenk (1984). A mutant of fowl plague virus (influenza A) with an altered glycosylation pattern in its hemagglutinin. Virology 136(1): 1-9.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  A temperature-sensitive mutant (ts 1/1) with a defect in the hemagglutinin (HA) gene, which was obtained by undiluted passage of fowl plague virus (FPV) at 33 degrees, is described. At 33 degrees proteolytic cleavage of the abnormal HA yielded an altered HA2 (XHA2) which migrated ahead of the NS1 protein and lacked the complex oligosaccharide side chain. At the nonpermissive temperature of 40 degrees, the migration of the HA of ts 1/1 from the rough endoplasmic reticulum (RER) via the Golgi apparatus to the cell surface was rate limiting for virus maturation. The HA was only slowly cleaved and migrated during polyacrylamide gel electrophoresis ahead of the HA of wild type FPV. Some revertants of ts 1/1 exhibited the same protein pattern as the mutant, others resembled wild type FPV, while one revertant gave rise to a mixture of HA2 and XHA2 at 40 degrees. These results suggest that (1) the loss of the complex oligosaccharide side chain is not responsible for the ts phenotype, (2) the mutation is presumably not at the site where the oligosaccharide side chain is linked to the protein backbone, and (3) ts 1/1 presumably carries a mutation located in RNA segment 4, which by pseudoreversion (suppressor mutation) in the same gene leads to different ts+ phenotypes.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus avian genetics, oligosaccharides analysis, cell membrane metabolism, cultured cells, chick embryo, endoplasmic reticulum metabolism, Golgi apparatus metabolism, hemagglutinins viral analysis, avian growth and development, avian immunology, mutation, phenotype, temperature.

Scholtissek, C. and S.B. Spring (1982). Extragenic suppression of temperature-sensitive mutations in RNA segment 8 by replacement of different rna segments with those of other influenza A virus prototype strains. Virology 118(1): 28-34.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian genetics, mutation, RNA viral genetics, suppression, genetic, crosses, genetic, genes viral, genetic markers, recombination, genetic, virus activation.

Scholtissek, C., J. Stech, S. Krauss, and R.G. Webster (2002). Cooperation between the hemagglutinin of avian viruses and the matrix protein of human influenza A viruses. Journal of Virology 76(4):  1781-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian genetics, human genetics, reassortant viruses, viral matrix proteins metabolism, amantadine pharmacology, antiviral agents pharmacology, cell line, dogs, drug resistance, viral, fowl plague virology, hemagglutinin glycoproteins, influenza virus genetics, influenza virology, avian drug effects, avian growth and development, avian metabolism, human drug effects, human growth and development, human metabolism, kidney cytology, kidney virology, plaque assay, poultry, viral matrix proteins genetics.

Scholtissek, C., A. Vallbracht, B. Flehmig, and R. Rott (1979). Correlation of pathogenicity and gene constellation of influenza A viruses. II. Highly neurovirulent recombinants derived from non-neurovirulent or weakly neurovirulent parent virus strains. Virology 95(2): 492-500.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes viral, influenza A virus pathogenicity, recombination, genetic, brain microbiology, chickens, influenza A virus avian genetics, human genetics, influenza A virus genetics, lung microbiology, mice, tissue culture, virulence.

Scholtissek, C. and V. von Hoyningen Huene (1980). Genetic relatedness of the gene which codes for the nonstructural (NS) protein of different influenza A strains. Virology 102(1): 13-20.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  genes, structural, genes viral, influenza A virus genetics, viral proteins genetics, base sequence, influenza A virus avian genetics, human genetics, porcine, nucleic acid hybridization, RNA viral analysis, RNA viral genetics.

Schroeder, C., H. Heider, B. Hegenscheid, M. Schoffel, V.I. Bubovich, and H.A. Rosenthal (1985). The anticholinergic anti-Parkinson drug Norakin selectively inhibits influenza virus replication. Antiviral Research (Suppl. 1): 95-9.  ISSN: 0166-3542.

            NAL Call Number:  QR355.A5

            Descriptors:  antiviral agents, biperiden pharmacology, influenza A virus avian drug effects, human drug effects, piperidines pharmacology, amantadine pharmacology, cell line, chick embryo, drug interactions, drug resistance, microbial, genes viral drug effects, hemagglutination, viral drug effects, hemolysis drug effects, avian physiology, human growth and development, human physiology, interferon type I biosynthesis, interferons pharmacology, measles virus drug effects, mutation, virus replication drug effects.

Schultz, C.S., M. Koci, E. Thompson, and T.M. Tumpey (2003). Examining the cellular pathways involved in influenza virus induced apoptosis. Avian Diseases 47(Special Issue): 968-971.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Apoptosis is essential in many physiological processes including wound healing and development of the immune response. Apoptosis also plays an important role in the pathogenesis of many infectious diseases including those caused by viruses. Influenza viruses induce apoptosis in cells that are permissive for viral replication and cells that do not support viral replication. The cellular pathways involved in influenza virus induced apoptosis are currently ill defined. Previous studies suggest that influenza virus infection increased the expression of the Fas antigen in HeLa cells, and that Fas antigen is partially involved in apoptosis. In these studies we examined the cellular pathways involved in avian influenza virus induced apoptosis in two cell lines that support productive viral replication: Madin-Darby canine kidney cells (MDCK) and mink lung epithelial (Mv1Lu) cells.

            Descriptors:  cell biology, infection, cellular pathways, immune response, physiological processes, viral replication, virally induced apoptosis, wound healing.

Schultz, U., W.M. Fitch, S. Ludwig, J. Mandler, and C. Scholtissek (1991). Evolution of pig influenza viruses. Virology 183(1): 61-73.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  There is evidence that the nucleoprotein (NP) gene of the classical swine virus (A/Swine/1976/31) clusters with the early human strains at the nucleotide sequence level, while at the level of the amino acid sequence, as defined by consensus amino acids and in functional tests, its NP is clearly "avian like." Therefore it was suggested that the Sw/31 NP had been recently under strong selection pressure, possibly caused by reassortment with other avian influenza genes, whose gene products have to cooperate intimately with NP (Gammelin et al., 1989. Virology 170, 71-80). This suggestion has been investigated by sequencing the genes of internal and nonstructural proteins of Sw/31. The data on these sequences and on the phylogenetic trees are not in accordance with that suggestion: all these genes cluster with the early human strains at the nucleotide level while, at the level of the amino acid sequence, most of them are more closely related to the avian strains, thus resembling NP in this respect. This indicates that these genes rather evolved concomitantly with the NP gene. Our data are in agreement with the suggestion that, at about the time of the Spanish Flu (1918/19), a human influenza A (H1N1) virus entered the pig population. Furthermore, it is known that the NP of the human influenza A viruses--in contrast to that of the avian and swine strains--has been under strong selection pressure to change (Gammelin et al., 1990. Mol. Biol. Evol. 7, 194-200. Gorman et al., 1990a. J. Virol. 64, 1487-1497). Thus, after transfer of a human strain into pigs, the selection pressure might be released, enabling the NP and the other genes of the swine virus to evolve back to the optimal avian sequences, especially at the functionally important consensus positions. The swine influenza viruses circulating since 1979 in Northern Europe--represented by A/Swine/Germany/2/81 (H1N1)--have all genes, so far examined, derived from an avian influenza virus pool and are different from the classical swine viruses.

            Descriptors:  influenza A virus, porcine genetics, phylogeny, RNA replicase, viral proteins genetics,  chick embryo, consensus sequence, genes viral, nucleoproteins genetics, swine, viral core proteins genetics.

Schuy, W., C. Will, K. Kuroda, C. Scholtissek, W. Garten, and H.D. Klenk (1986). Mutations blocking the transport of the influenza virus hemagglutinin between the rough endoplasmic reticulum and the Golgi apparatus. EMBO Journal 5(11): 2831-6.  ISSN: 0261-4189.

            NAL Call Number:  QH506.E46

            Abstract:  Mutants ts1 and ts227 of fowl plague virus have a temperature-sensitive defect in the transport of the hemagglutinin from the rough endoplasmic reticulum to the Golgi apparatus. The primary structure of the hemagglutinin of the mutants and of a number of revertants derived from them has been analysed by nucleotide sequencing. The transport block of the hemagglutinin of ts227 can be attributed to a single amino acid exchange. It involves the replacement of aspartic acid at position 457 by asparagine thereby introducing a new glycosylation site which appears to be located in a cryptic position in the lower part of the hemagglutinin stalk. Attachment of carbohydrate to this site is temperature-dependent. At permissive temperature only a small fraction of the monomers (approximately 30%) is glycosylated in this position, whereas at nonpermissive temperature this is the case with all subunits. The data suggest that under the latter conditions the new oligosaccharide interferes by steric hindrance with the trimerization of the hemagglutinin. The hemagglutinin of ts1 has an essential amino acid exchange at position 275 where serine is replaced by glycine. This substitution may increase the flexibility of the molecule in the hinge region between the globular domain and the stalk. The exchange of a conserved glutamic acid residue at position 398 that is involved in the interaction between different monomers contributes also to the structural instability of the ts1 hemagglutinin. These observations support the notion that the transport of the hemagglutinin from the rough endoplasmic reticulum to the Golgi apparatus depends on trimer assembly.

            Descriptors:  endoplasmic reticulum metabolism, Golgi apparatus metabolism, hemagglutinins viral genetics, influenza A virus avian genetics, mutation, base sequence, chick embryo, cloning, molecular, DNA analysis, DNA restriction enzymes, glycoproteins genetics, glycoproteins isolation and purification, models, molecular, protein conformation, RNA viral genetics, RNA viral isolation and purification.

Schwarz, R.T., B. Fournet, J. Montreuil, R. Rott, and H.D. Klenk (1978). The carbohydrates of influenza virus. II. Gas chromatographic analysis of glycopeptides derived from viral glycoproteins and mucopolysaccharides. Archives of Virology 56(3): 251-5.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Two carbohydrate fractions can be obtained from egg-grown influenza virus after Pronase digestion followed by gel chromatography. One fraction contains glycopeptides (MW ca. 2000--2600) which represent the carbohydrate side chains of the viral glycoproteins. The constituent sugars of this material are fucose, galactose, glucosamine, and mannose, and their position within the side chain has been partially elucidated by methylation studies. The other fraction (MW greatest than 6000) appears to be mucopolysaccharide and is composed of fucose, galactose, glucose, galactosamine, and glucosamine.

            Descriptors:  glycopeptides analysis, glycoproteins analysis, glycosaminoglycans analysis, influenza A virus avian analysis, influenza A virus analysis, chromatography, gas, fucose analysis, galactosamine analysis, galactose analysis, glucosamine analysis, glucose analysis, mannose analysis.

Schwarz, R.T. and H.D. Klenk (1981). Carbohydrates of influenza virus. IV. Strain-dependent variations. Virology 113(2): 584-93.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  glycoproteins analysis, hemagglutinins viral analysis, influenza A virus analysis, oligosaccharides analysis, viral proteins analysis, influenza A virus avian analysis, human analysis, porcine analysis, influenza A virus classification, serotyping, species specificity.

Schwarz, R.T. and H.D. Klenk (1974). Proceedings: Inhibition of glycosylation of the influenza virus hemagglutinin. Hoppe Seyler's Zeitschrift Fur Physiologische Chemie 355(10): 1254.  ISSN: 0018-4888.

            NAL Call Number:  384 Z38

            Descriptors:  glycoproteins biosynthesis, hemagglutinins viral metabolism, influenza A virus avian metabolism, viral proteins biosynthesis, deoxyglucose pharmacology, depression, chemical, glucosamine pharmacology.

Schwarz, R.T., J.M. Rohrschneider, and M.F. Schmidt (1976). Suppression of glycoprotein formation of Semliki Forest, influenza, and avian sarcoma virus by tunicamycin. Journal of Virology 19(3): 782-91.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Tunicamycin, a new antibiotic, halts the formation of physical particles of Semliki forest and fowl plague virus, whereas avian oncornavirus particles which show a reduction in infectivity and do not contain detectable labeled glycoprotein are released in the presence of the drug. In Semliki forest virus-infected cells only the protein moieties of the glycoproteins could be labeled. In cells infected with fowl plague and avian sarcoma virus neither intact glycoproteins nor their protein moieties could be detected. By using a protease inhibitor (N-alpha-p-tosyl-L-lysin chloromethyl ketone, TLCK) it could be shown, however, that the carbohydrate-free hemagglutinin precursor of influenza virus is synthesized but is presumably degraded by intracellular proteases in the absence of TLCK as a consequence of the lack of carbohydrate.

            Descriptors:  anti bacterial agents pharmacology, glycoproteins biosynthesis, influenza A virus avian drug effects, sarcoma viruses, avian drug effects, Semliki Forest virus drug effects, viral proteins biosynthesis, chick embryo, glucosamine analogs and derivatives,  glucosamine metabolism, glucosamine pharmacology, hemagglutinins viral analysis, avian metabolism, mannose metabolism, sarcoma viruses, avian metabolism, Semliki Forest virus metabolism, tissue culture, tosyllysine chloromethyl ketone pharmacology.

Schwarz, R.T. and C. Scholtissek (1973). Purification and properties of the RNA polymerase-template complex of an influenza virus. Zeitschrift Fur Naturforschung. Teil C Biochemie, Biophysik, Biologie, Virologie 28(3): 202-7.  ISSN: 0341-0471.

            NAL Call Number:  QH301.Z4

            Descriptors:  DNA directed RNA polymerases analysis, influenza A virus avian enzymology, adenosine triphosphate, chick embryo, RNA viral biosynthesis, templates, genetic.

Sears, S.D., M.L. Clements, R.F. Betts, H.F. Maassab, B.R. Murphy, and M.H. Snyder (1988). Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults. Journal of Infectious Diseases 158(6): 1209-19.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.

            Descriptors:  influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine, adult, antibodies, vi