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.<