Zoonotic Implications

 

 

Abbott, A. and D. Cyranoski (2004). Bird flu sparks worldwide bid to prevent human pandemic. Nature  427(6972): 274.  ISSN: 1476-4687.

            NAL Call Number:  472 N21

            Descriptors:  influenza prevention and control, influenza veterinary, poultry diseases epidemiology, zoonoses epidemiology, Asia epidemiology, influenza epidemiology, influenza transmission, influenza A virus, avian isolation and purification, poultry diseases prevention and control, poultry diseases transmission, poultry diseases virology, World Health Organization, zoonoses transmission, zoonoses virology.

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. (1998). Avian influenza viruses and pandemic influenza in humans. State Veterinary Journal (United Kingdom) 8(3): 8-10.

            NAL Call Number:  SF601.S8

            Descriptors:  avian influenza virus, viroses, mankind, zoonoses, pathogenicity, biological properties, infectious diseases, influenza virus, microbial properties, orthomyxoviridae, viruses, influenza.

Alexander, D.J. (2000). How dangerous are avian influenza viruses for humans? World Poultry (Special): 11-12.  ISSN: 1388-3119.

            NAL Call Number:  SF481.M54

            Descriptors:  zoonoses, pathogenesis, avian influenza virus,  poultry, humans, dangers.

Alexander, D.J. (1988). Influenza A isolations from exotic caged birds. Veterinary Record 123(17): 442.  ISSN: 0042-4900.

            NAL Call Number:  41.8 V641

            Descriptors:  birds microbiology, fowl plague epidemiology, influenza A virus avian isolation and purification, England, fowl plague microbiology, quarantine.

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.

Anonymous (1999). Avian strain of influenza A virus isolated from humans in Hong Kong. Communicable Disease Report. CDR Weekly 9(15): 131, 134.  ISSN: 1350-9357.

            Descriptors:  disease outbreaks, influenza epidemiology, influenza A virus avian, child, preschool, Hong Kong epidemiology, infant.

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.

Anonymous (1997). Influenza A virus subtype H5N1 infection in humans. Communicable Disease Report. CDR Weekly 7(50): 441.  ISSN: 1350-9357.

            Descriptors:  fowl plague transmission, influenza epidemiology, influenza A virus avian classification, adolescent, bacterial typing techniques,  chickens, child, preschool, fowl plague epidemiology, Hong Kong epidemiology, incidence, avian isolation and purification, middle aged, survival rate.

Anonymous (1998). Isolation of avian influenza A(H5N1) viruses from humans - Hong Kong, 1997-1998. MMWR. Morbidity and Mortality Weekly Report 46(52/53): 1245-1247.  ISSN: 0149-2195.

            NAL Call Number:  RA407.3.M56

            Descriptors:  avian influenza, human infection, transmission, Hong Kong.

Anonymous (1997). Isolation of avian influenza A(H5N1) viruses from humans--Hong Kong, May-December 1997. MMWR. Morbidity and Mortality Weekly Report 46(50): 1204-7.  ISSN: 0149-2195.

            NAL Call Number:  RA407.3.M56

            Abstract:  A strain of influenza virus that previously was known to infect only birds has been associated with infection and illness in humans in Hong Kong. The first known human case of influenza type A(H5N1) occurred in a 3-year-old child who died from respiratory failure in May 1997. In Hong Kong, the virus initially was identified as influenza type A, but the subtype could not be determined using standard reagents. By August, CDC; the National Influenza Center, Rotterdam, the Netherlands; and the National Institute for Medical Research, London, United Kingdom, had independently identified the virus as influenza A(H5N1). An investigation conducted during August-September by the Hong Kong Department of Health and CDC excluded the possibility of laboratory contamination. Since this initial case was identified, six additional persons in Hong Kong have been confirmed to have influenza A(H5N1) infection, and two possible cases have been identified. This report summarizes the nine cases identified thus far and describes preliminary findings from the ongoing investigation, which indicate that multiple influenza A(H5N1) infections have occurred and that both the source and mode of transmission are uncertain at this time.

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

Anonymous (2004). Lessons from the outbreak of avian influenza across Asia. Indian Veterinary Journal 81(3): A9.  ISSN: 0019-6479.

            NAL Call Number:  41.8 In2

            Descriptors:  avian influenza virus infection, quarantine, clinical techniques, Food and Agriculture Organization, United Nations, World Health Organization, Office International des Epizooties, Asia.

Anonymous (1998). Update: isolation of avian influenza A(H5N1) viruses from humans--Hong Kong, 1997-1998. MMWR. Morbidity and Mortality Weekly Report 46(52-53): 1245-7.  ISSN: 0149-2195.

            NAL Call Number:  RA407.3.M56

            Abstract:  As of January 6, 1998, a total of 16 confirmed and three suspected cases of human infection with avian influenza A(H5N1) viruses have been identified in Hong Kong. Confirmed cases are those from which an influenza A(H5N1) virus was isolated or in which a seroconversion to influenza A(H5N1) virus was detected by a neutralization assay. Suspected cases are those with influenza-like illness (ILI) and preliminary laboratory evidence of influenza A(H5N1) infection. This report summarizes interim findings from the ongoing epidemiologic and laboratory investigation of influenza A(H5N1) cases by health officials in Hong Kong and by CDC.

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

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.

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.

Ayoub, N.N.K., G. Heider, H. Glathe, K. Ziedler, D. Ebner, and E. Prusas (1974). Influenza-A-Antikorper (human) beim Geflugel. [Influenza A antibodies (human) in poultry]. Monatshefte Fur Veterinarmedizin 29(4): 139-143.  ISSN: 0026-9263.

            NAL Call Number:  41.8 M742

            Descriptors:  avian influenza virus, serum samples, turkeys,  fowl, zoonoses, human strains, Hong Kong strain, Singapore strain, antibodies.

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.

Banks, J., E. Speidel, and D.J. Alexander (1998). Characterisation of an avian influenza A virus isolated from a human--is an intermediate host necessary for the emergence of pandemic influenza viruses? Archives of Virology 143(4): 781-7.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The partial sequencing of the internal and the neuraminidase genes of isolate 268/96 obtained from a woman with conjunctivitis showed all seven to have closest homology with avian influenza viruses. The entire nucleotide sequence of the haemagglutinin gene of 268/96 had close, 98.2%, homology with an H7N7 virus isolated from turkeys in Ireland in 1995. This appears to be the first reported case of isolation of an influenza A virus from a human being infected as a result of direct natural transmission of an avian influenza virus from birds.

            Descriptors:  influenza virology, influenza A virus avian genetics, adult, birds virology, genes viral, influenza epidemiology, influenza transmission, avian classification, influenza A virus avian isolation and purification, Ireland, molecular sequence data, phylogeny, turkeys virology.

Barclay, W.S. and M. Zambon (2004). Pandemic risks from bird flu. BMJ Clinical Research 328(7434): 238-9.  ISSN: 1468-5833.

            Descriptors:  disease outbreaks, fowl plague epidemiology, influenza epidemiology, Asia, Southeastern epidemiology, birds, chickens, influenza A virus avian, human.

Baumeister, E.G. and V.L. Savy (1998). Human circulation of avian influenza (H5N1) in Hong Kong. Boletín De La Asociación Argentina De Microbiología (129): 12-13.  ISSN: 0325-6480.

            Descriptors:  human diseases, influenza virus A, epidemics, clinical aspects, diagnosis, reviews,  Hong Kong.

Beare, A.S. and R.G. Webster (1991). Replication of avian influenza viruses in humans. Archives of Virology 119(1-2): 37-42.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Volunteers inoculated with avian influenza viruses belonging to subtypes currently circulating in humans (H1N1 and H3N2) were largely refractory to infection. However 11 out of 40 volunteers inoculated with the avian subtypes, H4N8, H6N1, and H10N7, shed virus and had mild clinical symptoms: they did not produce a detectable antibody response. This was presumably because virus multiplication was limited and insufficient to stimulate a detectable primary immune response. Avian influenza viruses comprise hemagglutinin (HA) subtypes 1-14 and it is possible that HA genes not so far seen in humans could enter the human influenza virus gene pool through reassortment between avian and circulating human viruses.

            Descriptors:  influenza A virus avian pathogenicity, adult, antibodies, viral blood, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral immunology, avian isolation and purification, avian physiology, middle aged, species specificity, virus replication.

Beckford Ball, J. (2004). Building awareness of the avian flu outbreak and its symptoms. Nursing Times 100(6): 28-9.  ISSN: 0954-7762.

            Abstract:  The current outbreak of avian influenza in South East Asia has resulted in a small number of human deaths. Avian flu can pass from birds to humans, although the number of humans infected is low. The fear is that the avian flu virus could mutate in a human who was also infected with a common flu virus, creating a new strain that could pass from human to human. Nurses, especially those working in travel health, should keep themselves informed of the latest developments.

            Descriptors:  avian flu, outbreak, symptoms, South East Asia, human deaths, birds.

Belshe, R.B. (1998). Influenza as a zoonosis: how likely is a pandemic? Lancet  351(9101): 460-1.  ISSN: 0140-6736.

            NAL Call Number:  448.8 L22

            Descriptors:  disease outbreaks, fowl plague transmission, influenza transmission, influenza virology,  influenza A virus avian, zoonoses, Asia epidemiology, chickens virology, Hong Kong epidemiology, influenza epidemiology.

Bender, C., H. Hall, J. Huang, A. Klimov, N. Cox, A. Hay, V. Gregory, K. Cameron, W. Lim, and K. Subbarao (1999). Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998. Virology  254(1): 115-23.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza virology, influenza A virus human genetics, neuraminidase genetics, adolescent, adult, antigens, viral immunology, base sequence, child, preschool, DNA, viral, disease outbreaks, genes viral, Hong Kong epidemiology, infant, influenza epidemiology, human growth and development, human immunology, human isolation and purification, middle aged, molecular sequence data, phylogeny.

Berg, M., L. Englund, I.A. Abusugra, B. Klingeborn, and T. Linne (1990). Close relationship between mink influenza (H10N4) and concomitantly circulating avian influenza viruses. Archives of Virology 113(1-2): 61-71.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Strains of an influenza H10N4 virus have been isolated during an outbreak of a respiratory disease in mink on the south-east coast of Sweden. This was the first example of a disease in mammals caused by the H10 subtype. We compared the A/mink/Sweden/84 strain with two recent avian H10N4 isolates, one from fowl and another from a mallard, both isolated in Great Britain in 1985 as well as the prototype A/chicken/Germany/N/49 (H10N7). The comparison was carried out by genomic analysis of the strains by oligonucleotide fingerprinting and in bioassays on mink. The oligonucleotide fingerprint analysis revealed a high degree of genomic homology of around 98% between the viruses from mink, mallard and fowl. Only the recent avian isolates, that from the mallard and fowl could infect mink by contact, causing similar pathological and clinical signs and inducing seroconversion as did the mink virus. However, the susceptibility of mink to the fowl and mallard viruses by contact was less pronounced than that to the mink virus. Both the genomic homology and the similarities from the infectivity and pathogenicity studies between the mink virus and the recent avian isolates point to a direct invasion of the mink population by an avian H10N4 virus.

            Descriptors:  influenza A virus avian genetics, mink, orthomyxoviridae infections veterinary, chickens microbiology, disease outbreaks veterinary, ducks microbiology, fowl plague microbiology, fowl plague transmission, genes viral, avian isolation and purification, avian pathogenicity, nucleotide mapping, orthomyxoviridae infections microbiology, orthomyxoviridae infections transmission, RNA, viral, Sweden epidemiology.

Bikour, M.H., E.H. Frost, S. Deslandes, B. Talbot, and Y. Elazhary (1995). Persistence of a 1930 swine influenza A (H1N1) virus in Quebec. Journal of General Virology 76(Pt. 10): 2539-47.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Two antigenically distinct H1N1 influenza A viruses were isolated during an outbreak of respiratory disease in Quebec swine in 1990/91. Analysis of haemagglutinin and partial nucleoprotein sequences indicated that one was a variant of the swine H1N1 influenza virus circulating in the American Midwest whereas the other was very similar to virus isolated from swine in 1930. The existence of this latter isolate supports the concept that influenza viruses can be maintained for long periods in swine, perhaps in geographically limited pockets. Serological evidence indicates that these distinct strains continued to circulate widely in south-central Quebec until at least 1993.

            Descriptors:  influenza A virus, porcine genetics, influenza A virus, porcine immunology, orthomyxoviridae infections veterinary, phylogeny, swine diseases virology, amino acid sequence,  antigenic variation, antigens, viral analysis, base sequence, capsid genetics, disease outbreaks, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral analysis, hemagglutinins viral genetics, avian genetics, human genetics, molecular sequence data, orthomyxoviridae infections epidemiology, orthomyxoviridae infections virology, quebec epidemiology, sequence analysis, DNA, sequence homology, amino acid, swine, swine diseases epidemiology, viral core proteins genetics.

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.

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.

Bonn, D. (2004). Avian influenza: the whole world's business. Lancet Infectious Diseases 4(3): 128.  ISSN: 1473-3099.

            Descriptors:  ducks virology, avian influenza transmission, poultry diseases transmission, zoonoses, Asia epidemiology, food contamination, avian influenza epidemiology, poultry diseases epidemiology, public health.

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.

Bricaire, F. (2004). La grippe aviaire, quel risque de transmission interhumaine? [Avian flu, what are the risks of inter-human transmission?]. Presse Medicale Paris, France 1983 33(6): 366-7.  ISSN: 0755-4982.

            Descriptors:  disease outbreaks, influenza A virus, avian influenza, avian influenza epidemiology, avian influenza transmission, zoonoses, human, porcine, avian influenza prevention and control, poultry, risk factors, swine.

Bridges, C.B., W. Lim, J. Hu Primmer, L. Sims, K. Fukuda, K.H. Mak, T. Rowe, W.W. Thompson, L. Conn, X. Lu, N.J. Cox, and J.M. Katz (2002). Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997-1998. Journal of Infectious Diseases 185(8): 1005-10.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  In 1997, outbreaks of highly pathogenic influenza A (H5N1) among poultry coincided with 18 documented human cases of H5N1 illness. Although exposure to live poultry was associated with human illness, no cases were documented among poultry workers (PWs). To evaluate the potential for avian-to-human transmission of H5N1, a cohort study was conducted among 293 Hong Kong government workers (GWs) who participated in a poultry culling operation and among 1525 PWs. Paired serum samples collected from GWs and single serum samples collected from PWs were considered to be anti-H5 antibody positive if they were positive by both microneutralization and Western blot testing. Among GWs, 3% were seropositive, and 1 seroconversion was documented. Among PWs, approximately 10% had anti-H5 antibody. More-intensive poultry exposure, such as butchering and exposure to ill poultry, was associated with having anti-H5 antibody. These findings suggest an increased risk for avian influenza infection from occupational exposure.

            Descriptors:  influenza etiology, influenza A virus, occupational diseases etiology, poultry virology, adolescent, adult, case control studies,  Hong Kong epidemiology, influenza epidemiology, middle aged, occupational exposure, risk factors, seroepidemiologic studies, time factors.

Bright, R.A., D.S. Cho, T. Rowe, and J.M. Katz (2003). Mechanisms of pathogenicity of influenza A (H5N1) viruses in mice. Avian Diseases 47(Special Issue): 1131-1134.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Avian-like H5N1 influenza viruses isolated from humans in 1997 were shown to have two distinct pathogenic phenotypes in BALB/c mice, after intranasal inoculation and without prior adaptation to this host. To further understand the mechanisms of H5N1 pathogenicity, we investigated the consequences of the route of viral inoculation on morbidity and mortality, viral replication in pulmonary and systemic organs, and lymphocyte depletion. This study demonstrates the importance of extrapulmonary spread and replication, particularly in the brain, for the lethality of H5N1 viruses.

            Descriptors:  infection, avian influenza, infectious disease, respiratory system disease, viral disease, inoculation clinical techniques, therapeutic and prophylactic techniques, morbidity, mortality, pathogenic phenotypes, pathogenicity mechanisms, viral replication.

Brown, H. (2004). WHO confirms human-to-human avian flu transmission. Lancet  363(9407): 462.  ISSN: 1474-547X.

            NAL Call Number:  448.8 L22

            Descriptors:  disease transmission, horizontal statistics and numerical data, fowl plague transmission, Asia epidemiology, fowl plague epidemiology, fowl plague prevention and control, influenza A virus avian, poultry, World Health Organization, zoonoses epidemiology, zoonoses transmission.

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.

Brownlee, G.G. and E. Fodor (2001). The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 356(1416): 1871-1876.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  In 1982 we characterized the antigenic sites of the haemagglutinin of influenza A/PR/8/34, which is an influenza strain of the H1 subtype that was isolated from humans in 1934, by studying mutants which escaped neutralization by antibody. Four antigenic sites, namely Cb, Sa, Sb and Ca, were found to be located near the tip of the trimeric haemagglutinin spike. Based on the sequence of the haemagglutinin of the 1918 Spanish influenza, we can now specify the extent of divergence of antigenic sites of the haemagglutinin during the antigenic drift of the virus between 1918 and 1934. This divergence was much more extensive (40%) than the divergence (20%) in predicted antigenic sites between the 1918 Spanish influenza and an avian H1 subtype consensus sequence. These results support the hypothesis that the human 1918 pandemic originated from an avian virus of the Hl subtype that crossed the species barrier from birds to humans and adapted to humans, presumably by mutation and/or reassortment, shortly before 1918.

            Descriptors:  epidemiology, infection, molecular genetics, avian influenza, viral disease, pandemic influenza, epidemiology, respiratory system disease, viral disease, 1918 Spanish influenza pandemic, age related mortality, antigenic drift, antigenic site divergence, mortality rate, species barrier.

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.

Butterfield, W.K., C.H. Campbell, and K.F. Shortridge. (1978). Identification of nonavid influenza A viruses containing human subtypes of haemagglutinin and neuraminidase isolated from poultry in Hong Kong. In: Proceedings. Eighty second annual meeting of the United States Animal Health Association, Buffalo, New York, p. 325-331.

            NAL Call Number: 49.9 UN3R

            Descriptors: disease surveys, avian influenza virus, humans, poultry, Hong Kong.

Buxton Bridges, C., J.M. Katz, W.H. Seto, P.K. Chan, D. Tsang, W. Ho, K.H. Mak, W. Lim, J.S. Tam, M. Clarke, S.G. Williams, A.W. Mounts, J.S. Bresee, L.A. Conn, T. Rowe, J. Hu Primmer, R.A. Abernathy, X. Lu, N.J. Cox, and K. Fukuda (2000). Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. Journal of Infectious Diseases 181(1): 344-8.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

            Descriptors:  antibodies, viral blood, disease outbreaks, disease transmission, patient to professional, influenza transmission, influenza A virus avian immunology, adult, carrier state, cohort studies, avian classification, middle aged, retrospective studies, seroepidemiologic studies.

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.

Campbell, C.H., R.G. Webster, and S.S.J. Breese (1970). Fowl plague virus from man. Journal of Infectious Diseases 122(6): 513-6.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  influenza A virus avian isolation and purification, antigens analysis, chick embryo, chickens, cross reactions, hemagglutination inhibition tests, immune sera analysis, avian classification, avian immunology, avian pathogenicity, microscopy, electron, neuraminidase analysis, neutralization tests, poultry diseases immunology, vaccination, viral vaccines administration and dosage.

Campitelli, L., C. Fabiani, S. Puzelli, A. Fioretti, E. Foni, A. De Marco, S. Krauss, R.G. Webster, and I. Donatelli (2002). H3N2 influenza viruses from domestic chickens in Italy: an increasing role for chickens in the ecology of influenza? Journal of General Virology 83(Pt. 2): 413-20.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  In Italy, multiple H3N2 influenza viruses were isolated from chickens with mild respiratory disease and were shown to replicate in the respiratory tracts of experimentally infected chickens; this finding is the first to show that H3N2 influenza viruses can replicate and cause disease in chickens. H3N2 influenza viruses in pigs on nearby farms seemed a likely source of the virus; however, antigenic and molecular analyses revealed that the gene segments of the viruses in chickens were mainly of Eurasian avian origin and were distinguishable from those isolated from pigs and wild aquatic birds in Italy. Thus, several different H3 influenza viruses were circulating in Italy, but we failed to identify the source of the chicken H3N2 influenza viruses that have disappeared subsequently from Italian poultry. Until recently, the transmission of influenza viruses (other than the H5 and H7 subtypes) from their reservoir in aquatic birds to chickens was rarely detected and highly pathogenic and non-pathogenic viruses were considered to be restricted to poultry species. However, the recent reports of the transmission of H9N2 and H5N1 influenza viruses to chickens in Hong Kong and, subsequently, to humans and our findings of the transmission of H3N2 influenza viruses to domestic chickens in Italy suggest an increased role for chickens as an intermediate host in the ecology of influenza.

            Descriptors:  chickens, fowl plague virology, influenza veterinary, influenza A virus avian pathogenicity, poultry diseases virology, hemagglutination inhibition tests, hemagglutinin glycoproteins, influenza virus genetics, influenza virology, avian isolation and purification, avian physiology, porcine isolation and purification, porcine pathogenicity, Italy, molecular sequence data, sequence analysis, DNA, swine diseases virology, viral proteins genetics, virus replication.

Capua, I. and D.J. Alexander (2004). Human health implications of avian influenza viruses and paramyxoviruses. European Journal of Clinical Microbiology and Infectious Diseases Official Publication of the European Society of Clinical Microbiology 23(1): 1-6.  ISSN: 0934-9723.

            Abstract:  Among avian influenza viruses and avian paramyxoviruses are the aetiological agents of two of the most devastating diseases of the animal kingdom: (i). the highly pathogenic form of avian influenza, caused by some viruses of the H5 and H7 subtypes, and (ii). Newcastle disease, caused by virulent strains of APMV type 1. Mortality rates due to these agents can exceed 50% in naive bird populations, and, for some strains of AI, nearly 100%. These viruses may also be responsible for clinical conditions in humans. The virus responsible for Newcastle disease has been known to cause conjunctivitis in humans since the 1940s. The conjunctivitis is self-limiting and does not have any permanent consequences. Until 1997, reports of human infection with avian influenza viruses were sporadic and frequently associated with conjunctivitis. Recently, however, avian influenza virus infections have been associated with fatalities in human beings. These casualties have highlighted the potential risk that this type of infection poses to public health. In particular, the pathogenetic mechanisms of highly pathogenic avian influenza viruses in birds and the possibility of reassortment between avian and human viruses in the human host represent serious threats to human health. For this reason, any suspected case should be investigated thoroughly.

            Descriptors:  avulavirus isolation and purification, communicable disease control, disease outbreaks, fowl plague epidemiology, influenza A virus avian isolation and purification, Newcastle disease epidemiology, birds, fowl plague prevention and control, Italy epidemiology, Newcastle disease prevention and control, prognosis, risk assessment, survival analysis.

Capua, I., F. Mutinelli, M.D. Pozza, I. Donatelli, S. Puzelli, and F.M. Cancellotti (2002). The 1999-2000 avian influenza (H7N1) epidemic in Italy: veterinary and human health implications. Acta Tropica 83(1): 7-11.  ISSN: 0001-706X.

            NAL Call Number:  475 AC8

            Abstract:  From the end of March to the beginning of December 1999, 199 outbreaks of low pathogenicity avian influenza (LPAI) were diagnosed in the Veneto and Lombardia regions, which are located in the northern part of Italy. The virus responsible for the epidemic was characterized as a type A influenza virus of the H7N1 subtype of low pathogenicity. On the 17th of December, highly pathogenic avian influenza (HPAI) was diagnosed in a meat turkey flock in which 100% mortality was observed in 72 h. The infection spread to the industrial poultry population of northern Italy including chickens, guinea-fowl, quail, pheasants, ducks and ostriches for a total of 413 outbreaks. Over 13 million birds were affected by the epidemic, which caused dramatic economic losses to the Italian poultry industry with severe social and economic implications. The possibility of H7 virus transmission to humans in close contact with the outbreaks was evaluated through a serological survey. Seven hundred and fifty nine sera were collected and tested for the detection of anti-H7 antibodies by means of the micro-neutralization (MN) and single radial haemolysis (SRH) tests. All samples resulted negative. A limited number of clinical samples were also collected for attempted virus isolation with negative results. Current European legislation considers LPAI and HPAI as two completely distinct diseases, not contemplating any compulsory eradication policy for LPAI and requiring eradication for HPAI. Evidence collected during the Italian 1999-2000 epidemic indicates that LPAI due to viruses of the H7 subtype may mutate to HPAI, and, therefore, LPAI caused by viruses of the H5 or H7 subtypes must be controlled to avoid the emergence of HPAI. A reconsideration of the current definition of avian influenza adopted by the EU, could possibly be an aid to avoiding devastating epidemics for the poultry industry in Member States.

            Descriptors:  disease outbreaks, leishmaniasis, visceral epidemiology, adolescent, adult, age distribution, antibodies, protozoan isolation and purification, Brazil epidemiology, child, child preschool, infant, leishmaniasis, visceral immunology, prevalence, seroepidemiologic studies, skin tests, urban population.

Capua, I. and D.J. Alexander (2002). Avian influenza and human health. Acta Tropica 83(1): 1-6.  ISSN: 0001-706X.

            NAL Call Number:  475 AC8

            Abstract:  Natural infections with influenza A viruses have been reported in a variety of animal species including humans, pigs, horses, sea mammals, mustelids and birds. Occasionally devastating pandemics occur in humans. Although viruses of relatively few HA and NA subtype combinations have been isolated from mammalian species, all 15 HA subtypes and all 9 NA subtypes, in most combinations, have been isolated from birds. In the 20th century the sudden emergence of antigenically different strains transmissible in humans, termed antigenic shift, has occurred on four occasions, 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each time resulting in a pandemic. Genetic analysis of the isolates demonstrated that 'new' strains most certainly emerged after reassortment of genes of viruses of avian and human origin in a permissive host. The leading theory is that the pig represents the 'mixing vessel' where this genetic reassortment may occur. In 1996, an H7N7 influenza virus of avian origin was isolated from a woman with a self-limiting conjunctivitis. During 1997 in Hong Kong, an H5N1 avian influenza virus was recognised as the cause of death of 6 of 18 infected patients. Genetic analysis revealed these human isolates of H5N1 subtype to be indistinguishable from a highly pathogenic avian influenza virus that was endemic in the local poultry population. More recently, in March 1999, two independent isolations of influenza virus subtype H9N2 were made from girls aged one to four who recovered from flu-like illnesses in Hong Kong. Subsequently, five isolations of H9N2 virus from humans on mainland China in August 1998 were reported. H9N2 viruses were known to be widespread in poultry in China and other Asian countries. In all these cases there was no evidence of human to human spread except with the H5N1 infections where there was evidence of very limited spread. This is in keeping with the finding that all these viruses possessed all eight genes of avian origin. It may well be that infection of humans with avian influenza viruses occurs much more frequently than originally assumed, but due to their limited effect go unrecognised. For the human population as a whole the main danger of direct infection with avian influenza viruses appears to be if people infected with an 'avian' virus are infected simultaneously with a 'human' influenza virus. In such circumstances reassortment could occur with the potential emergence of a virus fully capable of spread in the human population, but with antigenic characteristics for which the human population was immunologically naive. Presumably this represents a very rare coincidence, but one which could result in a true influenza pandemic.

            Descriptors:  infection, avian influenza, respiratory system disease, viral disease, self limiting conjunctivitis, eye disease, genetic analysis genetic techniques, laboratory techniques.

Cauthen, A.N., D.E. Swayne, S. Schultz Cherry, M.L. Perdue, and D.L. Suarez (2000). Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans. Journal of Virology 74(14): 6592-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Since the outbreak in humans of an H5N1 avian influenza virus in Hong Kong in 1997, poultry entering the live-bird markets of Hong Kong have been closely monitored for infection with avian influenza. In March 1999, this monitoring system detected geese that were serologically positive for H5N1 avian influenza virus, but the birds were marketed before they could be sampled for virus. However, viral isolates were obtained by swabbing the cages that housed the geese. These samples, known collectively as A/Environment/Hong Kong/437/99 (A/Env/HK/437/99), contained four viral isolates, which were compared to the 1997 H5N1 Hong Kong isolates. Analysis of A/Env/HK/437/99 viruses revealed that the four isolates are nearly identical genetically and are most closely related to A/Goose/Guangdong/1/96. These isolates and the 1997 H5N1 Hong Kong viruses encode common hemagglutinin (H5) genes that have identical hemagglutinin cleavage sites. Thus, the pathogenicity of the A/Env/HK/437/99 viruses was compared in chickens and in mice to evaluate the potential for disease outbreaks in poultry and humans. The A/Env/HK/437/99 isolates were highly pathogenic in chickens but caused a longer mean death time and had altered cell tropism compared to A/Hong Kong/156/97 (A/HK/156/97). Like A/HK/156/97, the A/Env/HK/437/99 viruses replicated in mice and remained localized to the respiratory tract. However, the A/Env/HK/437/99 isolates caused only mild pathological lesions in these tissues and no clinical signs of disease or death. As a measure of the immune response to these viruses, transforming growth factor beta levels were determined in the serum of infected mice and showed elevated levels for the A/Env/HK/437/99 viruses compared to the A/HK/156/97 viruses. This study is the first to characterize the A/Env/HK/437/99 viruses in both avian and mammalian species, evaluating the H5 gene from the 1997 Hong Kong H5N1 isolates in a different genetic background. Our findings reveal that at least one of the avian influenza virus genes encoded by the 1997 H5N1 Hong Kong viruses continues to circulate in mainland China and that this gene is important for pathogenesis in chickens but is not the sole determinant of pathogenicity in mice. There is evidence that H9N2 viruses, which have internal genes in common with the 1997 H5N1 Hong Kong isolates, are still circulating in Hong Kong and China as well, providing a heterogeneous gene pool for viral reassortment. The implications of these findings for the potential for human disease are discussed.

            Descriptors:  fowl plague virology, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus avian genetics, poultry diseases virology, chickens, China epidemiology, disease outbreaks veterinary, fowl plague epidemiology, fowl plague pathology, Hong Kong epidemiology, immunohistochemistry, avian classification, avian pathogenicity, mice, mice inbred BALB c, molecular sequence data, phylogeny, poultry diseases epidemiology, poultry diseases pathology, sequence homology, nucleic acid, transforming growth factor beta blood.

Chan, P.K.S. (2002). Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clinical Infectious Diseases 34(Suppl. 2): S58-S64.  ISSN: 1058-4838.

            NAL Call Number:  RC111.R4

            Abstract:  The first outbreak of avian influenza A(H5N1) virus in humans occurred in Hong Kong in 1997. Infection was confirmed in 18 individuals, 6 of whom died. Infections were acquired by humans directly from chickens, without the involvement of an intermediate host. The outbreak was halted by a territory-wide slaughter of more than 1.5 million chickens at the end of December 1997. The clinical spectrum of H5N1 infection ranges from asymptomatic infection to fatal pneumonitis and multiple organ failure. Reactive hemophagocytic syndrome was the most characteristic pathologic finding and might have contributed to the lymphopenia, liver dysfunction, and abnormal clotting profiles that were observed among patients with severe infection. Rapid diagnosis with the use of reverse-transcription polymerase chain reaction and monoclonal antibody-based immunofluorescent assay were of great clinical value in the management of the outbreak. The experience of the H5N1 outbreak in Hong Kong underscores the importance of continuous surveillance of influenza virus strains in humans and in other animal species.

            Descriptors:  infection, public health, avian influenza A virus infection, symptom, viral disease, liver dysfunction, digestive system disease, lymphopenia, blood and lymphatic disease, immune system disease, multiple organ failure, disease miscellaneous, pneumonitis, respiratory system disease, reactive hemophagocytic syndrome, blood and lymphatic disease, monoclonal antibody based immunofluorescent assay diagnostic method, reverse transcriptase polymerase chain reaction diagnostic method, polymerase chain reaction, abnormal clotting profiles disease outbreak mortality.

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.

Claas, E.C., A.D. Osterhaus, R. van Beek, J.C. De Jong, G.F. Rimmelzwaan, D.A. Senne, S. Krauss, K.F. Shortridge, and R.G. Webster (1998). Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet  351(9101): 472-7.  ISSN: 0140-6736.

            NAL Call Number:  448.8 L22

            Abstract:  BACKGROUND: In May, 1997, a 3-year-old boy in Hong Kong was admitted to the hospital and subsequently died from influenza pneumonia, acute respiratory distress syndrome, Reye's syndrome, multiorgan failure, and disseminated intravascular coagulation. An influenza A H5N1 virus was isolated from a tracheal aspirate of the boy. Preceding this incident, avian influenza outbreaks of high mortality were reported from three chicken farms in Hong Kong, and the virus involved was also found to be of the H5 subtype. METHODS: We carried out an antigenic and molecular comparison of the influenza A H5N1 virus isolated from the boy with one of the viruses isolated from outbreaks of avian influenza by haemagglutination-inhibition and neuraminidase-inhibition assays and nucleotide sequence analysis. FINDINGS: Differences were observed in the antigenic reactivities of the viruses by the haemagglutination-inhibition assay. However, nucleotide sequence analysis of all gene segments revealed that the human virus A/Hong Kong/156/97 was genetically closely related to the avian A/chicken/Hong Kong/258/97. INTERPRETATION: Although direct contact between the sick child and affected chickens has not been established, our results suggest transmission of the virus from infected chickens to the child without another intermediate mammalian host acting as a "mixing vessel". This event illustrates the importance of intensive global influenza surveillance.

            Descriptors:  fowl plague virology, influenza virology, influenza A virus avian genetics, human genetics, amino acid sequence, base sequence, chickens virology, child, preschool, disease outbreaks veterinary, fowl plague epidemiology, Hong Kong epidemiology, influenza epidemiology, avian isolation and purification, avian pathogenicity, human isolation and purification, molecular sequence data.

Claas, E.C.J., Y. Kawaoka, J.C. de Jong, N. Masurel, and R.G. Webster (1994). Infection of children with avian-human reassortant influenza virus from pigs in Europe. Virology 204(1): 453-457.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Pigs have been proposed to act as the intermediate hosts in the generation of pandemic human influenza strains by reassortment of genes from avian and human influenza virus strains. The circulation of avian-like H1N1 influenza viruses in European pigs since 1979 and the detection of human-avian reassortants in pigs raises the question of whether these viruses actually have the potential to transmit and cause disease in humans. We now report the serologic and genetic characterization of two human influenza A viruses (A/Netherlands/5/93 [H3N2] and A/Netherlands/35/93 [H3N2]) that caused influenza in children in The Netherlands in 1993. The results show that these viruses are human-avian reassortants that were generated and currently still are circulating in European swine. This shows the pivotal role that pigs can play in the generation and transmission of avian influenza virus genes to humans and their potential to generate a new human pandemic strain.

            Descriptors:  swine, Netherlands, intermediate hosts, avian influenza virus, influenza virus, children, infection, disease transmission, genes, phylogeny, artiodactyla, biological competition, cell structure, chromosomes, disease transmission, domestic animals, Europe, evolution, hosts, influenza virus, livestock, mammals, nucleus, parasitism, pathogenesis, progeny, suidae, useful animals, viruses,  Western Europe, human influenza virus, pandemics, genetic reassortment, nucleoprotein genes, structural genes.

Claas, E.C.J. (2000). Pandemic influenza is a zoonosis, as it requires introduction of avian-like gene segments in the human population. Veterinary Microbiology 74(1-2): 133-139.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  Human influenza viruses manage to cause epidemics almost every year. The circulating viruses change their surface glycoproteins by accumulating mutations (antigenic drift) which results in variant viruses of the same subtype that are able to evade the immune pressure in the population. Every now and then, a completely new subtype of influenza A virus is introduced in the human population, which can result in an influenza pandemic. Pandemic human influenza viruses have been emerging for many centuries. Based on the genetic information of influenza viruses that have been isolated in this century, introduction of genes of the avian influenza virus reservoir obviously is required. Interspecies transmission, via another mammalian host and reassortment of avian and human influenza viruses are potential mechanisms for such an introduction. A summary of the cases in which influenza viruses containing avian-like gene segments were introduced into the human population is presented. In three cases, such infections resulted in conjunctivitis. Influenza-like illness and even pneumonia was reported in some other infections. Finally, a mortality rate of 33% was observed in the avian influenza A (H5N1) viruses that infected 18 people in Hong Kong in 1997. Although some of these viruses fulfilled some criteria of pandemic influenza viruses, they lacked the ability to rapidly spread through the human population.

            Descriptors:  molecular genetics, infection, epidemiology, conjunctivitis, eye disease, influenza virus infection, pandemic, viral disease, zoonosis, pneumonia, respiratory system disease, antigenic drift interspecies transmission mortality.

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.

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.

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.

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.

Cornell University - Department of Population Medicine & Diagnostic Sciences - Animal Health Diagnostic Center - College of Veterinary Medicine (2005). Canine Influenza Virus - Detection and Sampling.

            Online:  http://www.diaglab.vet.cornell.edu/issues/civ-dect.asp

            Abstract:  Canine influenza virus is a relatively new pathogen of dogs. It was first identified in racing greyhounds in 2004 and this virus appears to have been involved with significant respiratory problems on the dog tracks throughout the US for the last 2-3 years. The Virology Lab at Cornell isolated the first influenza virus from an animal that died during one of these clinical episodes. Evidence of infection of non-greyhounds by influenza virus has been found in Florida within the past year as part of the ongoing research efforts by Dr Cynda Crawford at the University of Florida on respiratory disease in dogs.

Couceiro, J.N., R.D. Machado, and J.R. Chaves (1982). Influenza A, isolamento e caracerizacao de virus isolados de aves de vida livre. [Influenza A, isolation and characterization of virus isolated from wild birds]. Anais De Microbiologia 27:  193-204.  ISSN: 0485-1854.

            Descriptors:  birds microbiology, influenza A virus avian isolation and purification, antigens, viral analysis, culture media, feces microbiology, hemagglutination inhibition tests, hemagglutinins viral analysis, immune sera, avian immunology, virus cultivation.

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.

de Boer, G.F., W. Back, and A.D. Osterhaus (1990). An ELISA for detection of antibodies against influenza A nucleoprotein in humans and various animal species. Archives of Virology 115(1-2): 47-61.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  A double antibody sandwich blocking ELISA, using a monoclonal antibody (MAb) against influenza A nucleoprotein (NP) was developed to detect antibodies against influenza. Collections of serum samples were obtained from human and various animal species. All influenza A subtypes induced antibodies against hemagglutinins and NP. A close correlation between titers of the hemagglutination inhibition (HI) test and the NP-ELISA was seen. Antibodies against influenza NP were demonstrated in serum samples from humans, ferrets, swine, horses, chickens, ducks, guinea pigs, mice, and seals. The serum samples were collected at intervals during prospective epidemiological studies, from experimental and natural infections, and vaccination studies. The decline of maternal antibodies was studied in swine and horses. The NP-ELISA enables rapid serological diagnosis and is suited for influenza A antibody screening, especially in species which harbor several influenza subtypes. The HI and neuraminidase inhibition tests, however, must still be used for subtyping.

            Descriptors:  antibodies, viral analysis, enzyme linked immunosorbent assay, influenza A virus immunology, nucleoproteins immunology, orthomyxoviridae infections immunology, viral core proteins immunology, ferrets, hemagglutination inhibition tests, horses, avian immunology, human immunology, porcine immunology, orthomyxoviridae infections veterinary, poultry, prospective studies, Rodentia, seals, species specificity, specific pathogen free organisms, swine, vaccination.

de Jong, J.C., E.C. Claas, and A.D. Osterhaus (1998). Influenza A (H5N1) in Hong Kong: voorbode van een pandemie of alleen een wetenschappelijk interessant verschijnsel en een nuttige oefening in pandemiologie? [Influenza A (H5N1) in Hong Kong: forerunner of a pandemic or an only scientifically interesting phenomenon and a useful exercise in pandemiology?]. Tijdschrift Voor Diergeneeskunde 123(9): 278-82.  ISSN: 0040-7453.

            NAL Call Number:  41.8 T431

            Abstract:  From a three-year old boy in Hong Kong who died in May 1997 with an extensive influenza pneumonia an influenza A virus has been isolated which was, first at the National Influenza Centre of the Netherlands, identified as belonging to subtype H5N1. Presumably the patient had acquired the infection directly from an outbreak of fowl plague among chickens. As far as is known this is the first case of the isolation of an influenza virus belonging to one of the subtypes H4-H15 from a human influenza patient. At the end of 1997 seventeen more cases of human A (H5N1) influenza have been detected in Hong Kong, including five fatal cases. Genetic analyses of seven of these virus isolates did not reveal the occurrence of reassortment with a human or porcine influenza virus, which could have rendered the virus potentially pandemic. Man-to-man transmission of the virus has not been demonstrated but cannot be excluded either. This event has shown that the WHO surveillance of influenza viruses, although perhaps not perfect, has functioned well.

            Descriptors:  influenza virology, influenza A virus avian isolation and purification, chickens, child preschool, disease outbreaks veterinary, epidemiologic methods, fowl plague epidemiology, fowl plague virology, influenza epidemiology, influenza transmission, avian classification, avian genetics, poultry,  poultry diseases epidemiology, poultry diseases virology, reassortant viruses genetics, zoonoses.

de Jong, J.C., G.F. Rimmelzwaan, R.A. Fouchier, and A.D. Osterhaus (2000). Influenza virus: a master of metamorphosis. Journal of Infection 40(3): 218-28.  ISSN: 0163-4453.

            Abstract:  Novel influenza viruses continuously emerge in the human population. Three times during the present century, an avian influenza virus subtype crossed the species barrier, starting a pandemic, and establishing itself for one to several decades in man. As the 1997 H5N1 event in Hong Kong indicated, the occurrence of another pandemic in the near future cannot be excluded. Sufficient vaccine may not be available to ameliorate the consequences of such an event, because of a shortage of time. During interpandemic periods, important antigenic drift variants sometimes arise at a point of time when, with the current state of the technique, production of a correspondingly adapted vaccine is also impossible. We may be able to solve these problems by increasing influenza surveillance and by adopting new ways of vaccine composition, production, formulation, presentation, and delivery. The recently developed anti-neuraminidase antivirals should only be considered as (valuable) adjuncts to vaccines.

            Descriptors:  antigenic variation, influenza epidemiology, orthomyxoviridae genetics, disease outbreaks, hn protein genetics, hemagglutinin glycoproteins, influenza virus genetics, influenza mortality, influenza prevention and control, influenza vaccine therapeutic use, orthomyxoviridae enzymology, orthomyxoviridae pathogenicity, reassortant viruses genetics, reassortant viruses pathogenicity, virulence.

de Jong, M.D., V.C. Bach, T.Q. Phan, M.H. Vo, T.T. Tran, B.H. Nguyen, M. Beld, T.P. Le, H.K. Truong, V.V. Nguyen, T.H. Tran, Q.H. Do, and J. Farrar (2005). Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New England Journal of Medicine 352(7): 686-91.  ISSN: 1533-4406.

            NAL Call Number:  448.8 N442

            Descriptors:  coma virology, diarrhea virology, encephalitis, viral etiology, influenza complications, influenza A virus, avian influenza genetics, avian influenza isolation and purification, acute disease, child, preschool child, viral virology, fatal outcome, influenza diagnosis, influenza virology, lung radiography, seizures virology.

Dea, S., M.A. Elazhary, and R.S. Roy (1980). Les virus influenza chez l'homme et les animaux. Une revue de la litterature. [Influenza viruses in man and animals. A literature review (author's transl)]. Canadian Veterinary Journal Revue Veterinaire Canadienne  21(6): 171-8.  ISSN: 0008-5286.

            NAL Call Number:  41.8 R3224

            Descriptors:  animals, domestic, orthomyxoviridae infections microbiology, orthomyxoviridae infections veterinary, antigens, viral analysis, chickens, epitopes, fowl plague microbiology, horse diseases microbiology, horses, influenza microbiology, influenza A virus avian immunology, human immunology, porcine immunology, mutation, recombination, genetic, swine, swine diseases microbiology.

DeLay, P.D., H.L. Casey, and H.S. Tubiash (1967). Comparative study of fowl plague virus and a virus isolated from man. Public Health Reports 82(7): 615-20.  ISSN: 0094-6214.

            NAL Call Number:  151.65 P96

            Descriptors:  influenza A virus avian immunology, orthomyxoviridae infections immunology, viruses immunology, chick embryo, haplorhini, hemagglutination inhibition tests, hemagglutination tests, neutralization tests, Newcastle disease immunology, Newcastle disease virus immunology, poultry, virus diseases immunology, virus diseases pathology.

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.

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.

Dybing, J.K., S. Schultz Cherry, D.E. Swayne, D.L. Suarez, and M.L. Perdue (2000). Distinct pathogenesis of hong kong-origin H5N1 viruses in mice compared to that of other highly pathogenic H5 avian influenza viruses. Journal of Virology 74(3):  1443-50.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian influenza viruses were analyzed for their pathogenicity in 6- to 8-week-old BALB/c mice. Both the avian and human HK H5 influenza virus isolates caused severe disease in mice, characterized by induced hypothermia, clinical signs, rapid weight loss, and 75 to 100% mortality by 6 to 8 days postinfection. Three of the non-HK-origin isolates caused no detectable clinical signs. One isolate, A/tk/England/91 (H5N1), induced measurable disease, and all but one of the animals recovered. Infections resulted in mild to severe lesions in both the upper and lower respiratory tracts. Most consistently, the viruses caused necrosis in respiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles with accompanying inflammation. The most severe and widespread lesions were observed in the lungs of HK avian influenza virus-infected mice, while no lesions or only mild lesions were evident with A/ck/Scotland/59 (H5N1) and A/ck/Queretaro/95 (H5N2). The A/ck/Italy/97 (H5N2) and the A/tk/England/91 (H5N1) viruses exhibited intermediate pathogenicity, producing mild to moderate respiratory tract lesions. In addition, infection by the different isolates could be further distinguished by the mouse immune response. The non-HK-origin isolates all induced production of increased levels of active transforming growth factor beta following infection, while the HK-origin isolates did not.

            Descriptors:  influenza virology, influenza A virus avian pathogenicity, human pathogenicity, hn protein, Hong Kong, immunohistochemistry, influenza pathology, avian isolation and purification, avian physiology, human isolation and purification, human physiology, mice, mice inbred BALB c, respiratory system pathology, respiratory system virology, transforming growth factor beta blood, virulence, virus replication.

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.

Edwards, L.E., D.C. Nguyen, X. Lu, H. Hall, A. Balish, J.E. Mabry, W. Lim, N.J. Cox, A. Klimov, and J.M. Katz (2004). Antigenic characteristics of recent avian influenza A H5N1 viruses isolated from humans. International Congress Series 1263: 109-113.

            Abstract:  Background: In February 2003, highly pathogenic avian influenza A H5N1 viruses reemerged in humans. Despite repeated outbreaks in domestic poultry in Hong Kong since 1999, this was the first isolation of H5N1 from humans since the outbreak in Hong Kong in 1997, which resulted in 18 human cases and 6 deaths. Methods: To better understand the antigenic relationship between the 2003 H5N1 human virus A/Hong Kong/213/03 (HK/213) and other H5 viruses, post-infection ferret sera or post-infection human sera were tested for reactivity by hemagglutination-inhibition and microneutralization assays with H5N1 viruses circulating in Hong Kong or elsewhere in Asia since 1997. Results: The H5N1 virus isolated from a 9-year-old male in Hong Kong was antigenically distinguishable from recent H5N1 viruses isolated from wild birds in Hong Kong and from the human 1997 H5N1 viruses, using post-infection ferret sera. Likewise, sera from this case patient, collected 22 days post-symptom onset, reacted to high titers with the homologous HK/213 virus, but gave eightfold lower titers with A/Hong Kong/156/97, and other H5 viruses. Conclusion: These results suggest that this recent human H5N1 virus is antigenically distinguishable from current and previously circulating H5N1 viruses from Asia, including the viruses previously isolated from humans.

            Descriptors:  influenza H5N1, antigenicity, serology.

Eiros Bouza, J.M. (2004). Sindrome agudo respiratorio grave y gripe aviar [Severe acute respiratory syndrome and avian flu]. Anales De La Real Academia Nacional De Medicina 121(2): 263-88.  ISSN: 0034-0634.

            Abstract:  Severe acute respiratory syndrome (SARS) is a new disease that caused large ourbreaks in several countries in the first half of 2003, resulting in infection in more than 8.000 people and more than 900 deaths. The disease originated in southern China and a novel coronavirus (SARS CoV) has been implicated as the causative organism. We present an overview of the etiology, clinical presentation and diagnosis, based on the current state of knowledge derived from published studies and our experience in the National Microbiology Centre. Influenza is a zoonosis. This appreciation of influenza ecology facilitated recognition of the H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of virus for humans and. The current outbreak of avian influenza in South East Asia has resulted in a small number of human deaths. These findings highlight the importance of systematic virus surveillance of domestic poultry in recognizing changes in virus occurrence, host range and pathogenicity as signals at the avian level that could presage a pandemic.

            Descriptors:  disease outbreaks, avian influenza epidemiology, severe acute respiratory syndrome diagnosis, severe acute respiratory syndrome etiology, severe acute respiratory syndrome virology, southeastern Asia epidemiology, China epidemiology, diagnosis, avian influenza mortality, avian influenza virology, middle aged adult.

Englund, L. (1996). The pathogenesis of avian influenza infection in mink (Mustela vison). In: Research and Development for Animal Health, Statens Veterinaermedicinska Anstalt: Uppsala (Sweden), p. 96-97. ISBN: 91-972469-0-5.

            Descriptors:  minks, viroses, avian influenza virus, pathogenesis, Carnivora, infectious diseases, influenza virus, mammals, Mustelidae, orthomyxoviridae, viruses.

Englund, L. (2000). Studies on influenza viruses H10N4 and H10N7 of avian origin in mink. Veterinary Microbiology 74(1-2): 101-107.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  An influenza A virus, A/mink/Sweden/84 (H10N4), was isolated from farmed mink during an outbreak of respiratory disease, histopathologically characterised by severe interstitial pneumonia. The virus was shown to be of recent avian origin and closely related to concomitantly circulating avian influenza virus. Serological investigations were used to link the isolated virus to the herds involved in the disease outbreak. Experimental infection of adult mink with the virus isolate from the disease outbreak reproduced the disease signs and pathological lesions observed in the field cases. The mink influenza virus also induced an antibody response and spread between mink by contact. The same pathogenesis in mink was observed for two avian influenza viruses of the H10N4 subtype, circulating in the avian population. When mink were infected with the prototype avian H10 influenza virus, A/chicken/Germany/N/49, H10N7, the animals responded with antibody production and mild pulmonary lesions but neither disease signs nor contact infections were observed. Detailed studies, including demonstration of viral antigen in situ by immunohistochemistry, of the sequential development of pathological lesions in the mink airways after aerosol exposure to H10N4 or H10N7 revealed that the infections progress very similarly during the first 24 h, but are distinctly different at later stages. The conclusion drawn is that A/mink/Sweden/84, but not A/chicken/Germany/N/49, produces a multiple-cycle replication in mink airways. Since the viral distribution and pathological lesions are very similar during the initial stages of infection we suggest that the two viruses differ in their abilities to replicate and spread within the mink tissues, but that their capacities for viral adherence and entry into mink epithelial cells are comparable.

            Descriptors:  animal husbandry, infection, respiratory system, influenza A virus infection, transmission, viral disease, pneumonia, interstitial, respiratory system disease, severe, respiratory disease, respiratory system disease, immunohistochemistry immunohistochemical, immunocytochemical techniques, analytical method, antibody response viral adherence.

Englund, L. and C. Hard af Segerstad (1998). Two avian H10 influenza A virus strains with different pathogenicity for mink (Mustela vison). Archives of Virology 143(4): 653-66.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  We compared two strains of avian influenza A viruses of subtype H10 by exposing mink to aerosols of A/mink/Sweden/3,900/84 (H10N4) naturally pathogenic for mink, or A/chicken/Germany/N/49, (H10N7). Lesions in the respiratory tract during the first week after infection were studied and described. Both virus strains caused inflammatory reactions in the lungs and antibody production in exposed mink but only mink/84 virus was reisolated. The lesions caused by mink/84 virus were more severe with higher area density of pneumonia, lower daily weight gain, and more virus in the tissues detected by immunohistochemistry. The results indicate that mink/84 (H10N4), but not chicken/49 virus (H10N7), established multiple cycle replication in infected cells in the mink.

            Descriptors:  influenza veterinary, influenza A virus avian pathogenicity, mink virology, antibodies, viral analysis, influenza physiopathology, influenza virology, lung virology, nasal mucosa virology, species specificity.

Englund, L., B. Klingeborn, and T. Mejerland (1986). Avian influenza A virus causing an outbreak of contagious interstitial pneumonia in mink. Acta Veterinaria Scandinavica 27(4): 497-504.  ISSN: 0044-605X.

            NAL Call Number:  41.8 AC87

            Descriptors:  disease outbreaks veterinary, influenza A virus avian pathogenicity, mink microbiology, veterinary viral pneumonia viral pneumonia epidemiology, viral pneumonia microbiology, viral pneumonia pathology, Sweden.

Enserink, M. (2004). Influenza: girding for disaster. Looking the pandemic in the eye. Science 306(5695): 392-4.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Descriptors:  disease outbreaks, influenza epidemiology, world health, cost of illness, influenza transmission, influenza virology, avian pathogenicity, influenza A virus, avian physiology, influenza vaccines administration and dosage, influenza vaccines supply and distribution, models, biological, orthomyxoviridae pathogenicity, orthomyxoviridae physiology, public health, reassortant viruses.

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.

Fanning, T.G., R.D. Slemons, A.H. Reid, T.A. Janczewski, J. Dean, and J.K. Taubenberger (2002). 1917 avian influenza virus sequences suggest that the 1918 pandemic virus did not acquire its hemagglutinin directly from birds. Journal of Virology 76(15): 7860-2.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Wild waterfowl captured between 1915 and 1919 were tested for influenza A virus RNA. One bird, captured in 1917, was infected with a virus of the same hemagglutinin (HA) subtype as that of the 1918 pandemic virus. The 1917 HA is more closely related to that of modern avian viruses than it is to that of the pandemic virus, suggesting (i) that there was little drift in avian sequences over the past 85 years and (ii) that the 1918 pandemic virus did not acquire its HA directly from a bird.

            Descriptors:  birds virology, evolution, molecular, hemagglutinin glycoproteins, influenza virus genetics, influenza history, influenza A virus avian genetics, influenza A virus human genetics, fowl plague history, fowl plague virology, hemagglutinin glycoproteins, influenza virus history, history of medicine, 20th century, influenza epidemiology, influenza virology, molecular sequence data,  phylogeny, RNA viral genetics, viral history,  sequence analysis, DNA.

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.

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.

Fleck, F. (2004). Avian flu virus could evolve into dangerous human pathogen, experts fear. Bulletin of the World Health Organization 82(3): 236-7.  ISSN: 0042-9686.

            NAL Call Number:  449.9 W892B

            Descriptors:  influenza epidemiology, influenza A virus, avian pathogenicity, zoonoses, Asia, birds.

Fomsgaard, A., P.C. Grauballe, and S.O. Glismann (2004). Risiko for en ny influenzapandemi? [Risk of a new influenza pandemic?]. Ugeskrift for Laeger 166(10): 912-5.  ISSN: 0041-5782.

            Descriptors:  disease outbreaks prevention and control, influenza epidemiology, influenza A virus classification, influenza A virus genetics, influenza A virus pathogenicity, zoonoses virology, birds, communicable disease control, influenza prevention and control, influenza transmission, avian influenza transmission, poultry, world health, zoonoses transmission.

Fouchier, R.A., G.F. Rimmelzwaan, T. Kuiken, and A.D. Osterhaus (2005). Newer respiratory virus infections: human metapneumovirus, avian influenza virus, and human coronaviruses. Current Opinion in Infectious Diseases 18(2): 141-6.  ISSN: 0951-7375.

            Abstract:  PURPOSE OF REVIEW: Recently, several previously unrecognized respiratory viral pathogens have been identified and several influenza A virus subtypes, previously known to infect poultry and wild birds, were transmitted to humans. Here we review the recent literature on these respiratory viruses. RECENT FINDINGS: Human metapneumovirus has now been detected worldwide, causing severe respiratory tract illnesses primarily in very young, elderly and immunocompromised individuals. Animal models and reverse genetic techniques were designed for human metapneumovirus, and the first vaccine candidates have been developed. Considerable genetic and antigenic diversity was observed for human metapneumovirus, but the implication of this diversity for vaccine development and virus epidemiology requires further study. Two previously unrecognized human coronaviruses were discovered in 2004 in The Netherlands and Hong Kong. Their clinical impact and epidemiology are largely unknown and warrant further investigation. Several influenza A virus subtypes were transmitted from birds to humans, and these viruses continue to constitute a pandemic threat. The clinical symptoms associated with these zoonotic transmissions range from mild respiratory illnesses and conjunctivitis to pneumonia and acute respiratory distress syndrome, sometimes resulting in death. More basic research into virus ecology and evolution and development of effective vaccines and antiviral strategies are required to limit the impact of influenza A virus zoonoses and the threat of an influenza pandemic. SUMMARY: Previously unknown and emerging respiratory viruses are an important threat to human health. Development of virus diagnostic tests, antiviral strategies, and vaccines for each of these pathogens is crucial to limit their impact.

            Descriptors:  coronavirus infections epidemiology, influenza virology, avian influenza A virus, metapneumovirus, paramyxoviridae infections epidemiology, respiratory tract infections virology, emerging communicable diseases, disease outbreaks, influenza epidemiology, risk factors, paramyxoviridae infections virology, coronavirus infections virology, influenza epidemiology.

Fouchier, R.A., P.M. Schneeberger, F.W. Rozendaal, J.M. Broekman, S.A. Kemink, V. Munster, T. Kuiken, G.F. Rimmelzwaan, M. Schutten, G.J. Van Doornum, G. Koch, A. Bosman, M. Koopmans, and A.D. Osterhaus (2004). Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proceedings of the National Academy of Sciences of the United States of America 101(5): 1356-61.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between the end of February and the end of May 2003, a fowl plague outbreak occurred in The Netherlands. A highly pathogenic avian influenza A virus of subtype H7N7, closely related to low pathogenic virus isolates obtained from wild ducks, was isolated from chickens. The same virus was detected subsequently in 86 humans who handled affected poultry and in three of their family members. Of these 89 patients, 78 presented with conjunctivitis, 5 presented with conjunctivitis and influenza-like illness, 2 presented with influenza-like illness, and 4 did not fit the case definitions. Influenza-like illnesses were generally mild, but a fatal case of pneumonia in combination with acute respiratory distress syndrome occurred also. Most virus isolates obtained from humans, including probable secondary cases, had not accumulated significant mutations. However, the virus isolated from the fatal case displayed 14 amino acid substitutions, some of which may be associated with enhanced disease in this case. Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.

            Descriptors:  conjunctivitis etiology, fowl plague epidemiology, influenza A virus avian isolation and purification, respiratory distress syndrome, adult etiology, amino acid sequence, birds, disease outbreaks, fatal outcome, fowl plague virology, hemagglutinin glycoproteins, influenza virus chemistry, influenza A virus avian classification, middle aged, molecular sequence data, Netherlands epidemiology, respiratory distress syndrome, adult pathology.

Fukumi, H., K. Nerome, M. Nakayama, and M. Ishida (1977). Serological and virological investigations fo orthomyxovirus in birds in South-East Asian area. Developments in Biological Standardization 39: 475-60.  ISSN: 0301-5149.

            NAL Call Number:  QR180.3.D4

            Abstract:  We have previously reported that some species of migrating ducks (pintail, mallard, widgeon and falcated teal) possess in their sera antibodies against H antigens of human or avian influenza viruses. Such findings have also been reported from other workers, and the appearance of new types of influenza viruses accompanied by outbreaks of new influenza pandemics, or circulation of influenza virus antigens in animals, birds and humans have been discussed on the basis of such findings. Recently a number of orthomyxoviruses have been isolated from wild birds such as myna, banded parakeets, etc. imported from India and some areas of South-East Asia. Some of them have H antigens not recognized previously, and some are found to have more or less common reactions with human H3 antigen, and consequently antigens Hav 7 and Heq 2, which are known to show cross-reaction with H3. The significance of such a fact in connection with the appearance of a new influenza pandemic is discussed.

            Descriptors:  antibodies, viral, birds microbiology, influenza A virus avian immunology, Asia, Southeastern, ducks, hemagglutinins viral, influenza A virus avian isolation and purification, Japan, neuraminidase immunology.

Gandolfi, P. (2004). Influenza aviaria ed epidemia nei Paesi del sud-est asiatico. [Avian influenza and the epidemic in the countries of South East Asia]. Rivista Di Avicoltura 73(3): 26-32.  ISSN: 1722-6945.

            NAL Call Number:  47.8 R523

            Descriptors:  avian influenza virus, disease control, epidemic, poultry, zoonoses, South East Asia.

Gao, P., S. Watanabe, T. Ito, H. Goto, K. Wells, M. McGregor, A.J. Cooley, and Y. Kawaoka (1999). Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. Journal of Virology 73(4): 3184-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997. Although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and PC6 proteases, it is not known whether it also causes systemic infection in humans. The clinical outcomes of infection in Hong Kong residents ranged widely, from mild respiratory disease to multiple organ failure leading to death. Therefore, to understand the pathogenesis of influenza due to these H5N1 isolates, we investigated their virulence in mice. The results identified two distinct groups of viruses: group 1, for which the dose lethal for 50% of mice (MLD50) was between 0.3 and 11 PFU, and group 2, for which the MLD50 was more than 10(3) PFU. One day after intranasal inoculation of mice with 100 PFU of group 1 viruses, the virus titer in lungs was 10(7) PFU/g or 3 log units higher than that for group 2 viruses. Both types of viruses had replicated to high titers (>10(6) PFU/g) in the lungs by day 3 and maintained these titers through day 6. More importantly, only the group 1 viruses caused systemic infection, replicating in nonrespiratory organs, including the brain. Immunohistochemical analysis demonstrated the replication of a group 1 virus in brain neurons and glial cells and in cardiac myofibers. Phylogenetic analysis of all viral genes showed that both groups of Hong Kong H5N1 viruses had formed a lineage distinct from those of other viruses and that genetic reassortment between H5N1 and H1 or H3 human viruses had not occurred. Since mice and humans harbor both the furin and the PC6 proteases, we suggest that the virulence mechanism responsible for the lethality of influenza viruses in birds also operates in mammalian hosts. The failure of some H5N1 viruses to produce systemic infection in our model indicates that multiple, still-to-be-identified, factors contribute to the severity of H5N1 infection in mammals. In addition, the ability of these viruses to produce systemic infection in mice and the clear differences in pathogenicity among the isolates studied here indicate that this system provides a useful model for studying the pathogenesis of avian influenza virus infection in mammals.

            Descriptors:  genes viral, influenza virology, influenza A virus physiology, variation genetics, Hong Kong epidemiology, immunohistochemistry, influenza epidemiology, mice, phylogeny, virus replication genetics.

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.

Geraci, J.R., D.J. St Aubin, I.K. Barker, V.S. Hinshaw, R.G. Webster, and H.L. Ruhnke (1984). Susceptibility of grey (Halichoerus grypus) and harp (Phoca groenlandica) seals to the influenza virus and mycoplasma of epizootic pneumonia of harbor seals (Phoca vitulina). Canadian Journal of Fisheries and Aquatic Sciences 41(1): 151-156.  ISSN: 0706-652X.

            NAL Call Number:  442.9 C16J

            Descriptors:  influenza virus, experimental infection, surveys, pneumonia, mycoplasmosis, Halichoerus grypus, Phoca groenlandica, Phoca vitulina.

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.

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.

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.

Gourreau, J.M., C. Kaiser, M. Valette, A.R. Douglas, J. Labie, and M. Aymard (1994). Isolation of two H1N2 influenza viruses from swine in France. Archives of Virology 135(3-4): 365-82.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Samples collected in 1987 and 1988 in Brittany from influenza-infected swine made it possible to isolate and antigenically characterize two H1N2 recombinant viruses (Sw/France/5027/87 and Sw/France/5550/88). The former virus was cloned and reinoculated to swine to allow reproduction of the disease and reisolation of a strain similar to the original one. The serodiagnostic tests carried out on both the original sera and those from the experimentally infected animals confirmed that the virus was actually type Sw/H1N2.

            Descriptors:  influenza A virus, porcine isolation and purification, swine virology, antibodies, monoclonal, antibody formation, antigens, viral analysis, birds, cloning, molecular, France, influenza immunology, influenza A virus avian classification, influenza A virus avian isolation and purification, influenza A virus human classification, influenza A virus human isolation and purification, influenza A virus, porcine genetics,  influenza A virus, porcine immunology, variation genetics.

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. 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.

Guan, Y., J.S.M. Peiris, A.S. Lipatov, T.M. Ellis, K.C. Dyrting, S. Krauss, L.J. Zhang, R.G. Webster, and K.F. Shortridge (2002). Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proceedings of the National Academy of Sciences of the United States of America 99(13): 8950-8955.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Although A/Hong Kong/156/97 (H5N1/97)-like viruses associated with the "bird flu" incident in Hong Kong SAR have not been detected since the slaughter of poultry in 1997, its putative precursors continue to persist in the region. One of these, Goose/Guangdong/1/96 (H5N1 Gs/Gd)-like viruses, reassorted with other avian viruses to generate multiple genotypes of H5N1 viruses that crossed to chickens and other terrestrial poultry from its reservoir in geese. Whereas none of these recent reassortants had acquired the gene constellation of H5N1/97, these events provide insight into how such a virus may have been generated. The recent H5N1 reassortants readily infect and kill chicken and quail after experimental infection, and some were associated with significant mortality of chickens within the poultry retail markets in Hong Kong. Some genotypes are lethal for mice after intra-nasal inoculation and spread to the brain. On this occasion, the early detection of H5N1 viruses in the retail, live poultry markets led to preemptive intervention before the occurrence of human disease, but these newly emerging, highly pathogenic H5N1 viruses provide cause for pandemic concern.

            Descriptors:  avian influenza virus, genotypes, genes, viral hemagglutinins, sialidase, nucleotide sequences, phylogenetics, strains, isolation, abattoirs, chickens, geese, ducks, pheasants, pathogenicity, experimental infections, mice, quails, hemagglutination inhibition test, amino acid sequences, Hong Kong, molecular sequence data, gene reassortants.

Guan, Y., J.S.M. Peiris, L.L.M. Poon, K.C. Dyrting, T.M. Ellis, L. Sims, R.G. Webster, and K.F. Shortridge (2003). Reassortants of H5N1 influenza viruses recently isolated from aquatic poultry in Hong Kong SAR. Avian Diseases 47(Special Issue): 911-913.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The H5N1 virus (H5N1/97) that caused the bird flu incident in Hong Kong in 1997 has not been isolated since the poultry slaughter in late 1997. But the donor of its H5 hemagglutinin gene, Goose/Guangdong/1/96-like (Gs/Gd/96-like) virus, established a distinct lineage and continued to circulate in geese in the area. In 2000, a virus from the Goose/Guangdong/1/96 lineage was isolated for the first time from domestic ducks. Subsequently, it has undergone reassortment, and these novel reassortants now appear to have replaced Gs/Gd/96-like viruses from its reservoir in geese and from ducks. The internal gene constellation is also different from H5N1/97, but these variants have the potential for further reassortment events that may allow the interspecies transmission of the virus.

            Descriptors:  epidemiology, infection, avian influenza, infectious disease, respiratory system disease, viral disease, interspecies viral transmission, viral lineage, viral reservoir.

Guan, Y., M. Peiris, K.F. Kong, K.C. Dyrting, T.M. Ellis, T. Sit, L.J. Zhang, and K.F. Shortridge (2002). H5N1 influenza viruses isolated from geese in Southeastern China: evidence for genetic reassortment and interspecies transmission to ducks. Virology 292(1): 16-23.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The H5N1 viruses (H5N1/97) associated with the "bird-flu" incident in the Hong Kong SAR have not been isolated since the slaughter of poultry in December 1997 brought that outbreak to an end. Recent evidence points to this virus as having arisen through a reassortment of a number of precursor avian viruses and a virus related to Goose/Guangdong/1/96 (H5N1) (Gs/Gd/96) was the likely donor of the H5 hemagglutinin. We characterize the Goose/Guangdong/1/96-like viruses isolated from geese and ducks imported into Hong Kong in the year 2000. Antigenically and genetically, these recent H5N1 viruses fall into two groups, one mainly associated with geese, and the other, recently transmitted to ducks. Further, viruses isolated from a goose and a duck in December 2000 have acquired NS, PA, M, and PB2 genes from the aquatic avian influenza gene pool through reassortment. For pandemic preparedness, it is important to monitor whether these reassortant viruses have the capacity for interspecies transmission to terrestrial poultry or mammals.

            Descriptors:  ducks virology, fowl plague transmission, geese virology, influenza A virus avian genetics, poultry diseases transmission, China, evolution, molecular, fowl plague virology, influenza A virus avian isolation and purification, molecular sequence data, phylogeny, poultry diseases virology, recombination, genetic, sequence analysis, DNA.

Guan, Y., L.L. Poon, C.Y. Cheung, T.M. Ellis, W. Lim, A.S. Lipatov, K.H. Chan, K.M. Sturm Ramirez, C.L. Cheung, Y.H. Leung, K.Y. Yuen, R.G. Webster, and J.S. Peiris (2004). H5N1 influenza: a protean pandemic threat. Proceedings of the National Academy of Sciences of the United States of America 101(21): 8156-61.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  Infection with avian influenza A virus of the H5N1 subtype (isolates A/HK/212/03 and A/HK/213/03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A/HK/212/03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.

            Descriptors:  influenza epidemiology, influenza virology, birds virology, cytokines biosynthesis, cytokines immunology, hemagglutination inhibition tests, Hong Kong, inflammation mediators immunology, influenza transmission, influenza veterinary, influenza A virus, avian classification, avian genetics, avian immunology, avian pathogenicity, macrophages immunology, macrophages metabolism, mice, molecular sequence data, organ specificity, phylogeny, reassortant viruses immunology, reassortant viruses pathogenicity, time factors, virulence.

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.

Guan, Y., K.F. Shortridge, S. Krauss, P.H. Li, Y. Kawaoka, and R.G. Webster (1996). Emergence of avian H1N1 influenza viruses in pigs in China. Journal of Virology 70(11): 8041-8046.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Avian influenza A viruses from Asia are recognized as the source of genes that reassorted with human viral genes to generate the Asian/57 (H2N2) and Hong Kong/68 (H3N2) pandemic strains earlier in this century. Here we report the genetic analysis of avian influenza A H1N1 viruses recently isolated from pigs in southern China, a host suspected to generate new pandemic strains through gene reassortment events. Each of the eight gene segments was of avian origin. Phylogenetic analysis indicates that these genes form an Asian sublineage of the Eurasian avian lineage, suggesting that these viruses are an independent introduction into pigs in Asia. The presence of avian influenza viruses in pigs in China places them in an optimal position for transmission to humans and may serve as an early warning of the emergence of the next human influenza virus pandemic.

            Descriptors:  Hunan, Jiangxi, Guizhou, Guangdong, swine, avian influenza virus, nucleotide sequence, genes, agglutinins, swine influenza virus, influenza virus, genotypes, mutation, animal viruses, proteins, nucleoproteins, Asia, cell structure, China, chromosomes, domestic animals, East Asia, genetics, genomes, influenza virus, livestock, nucleus, orthomyxoviridae, proteins, suidae, useful animals, viruses, nonstructural proteins, isolation, phylogenetics, structural genes, viral hemagglutinins, influenza virus A, matrix proteins.

Guan, Y., K.F. Shortridge, S. Krauss, and R.G. Webster (1999). Molecular characterization of H9N2 influenza viruses: were they the donors of the "internal" genes of H5N1 viruses in Hong Kong? Proceedings of the National Academy of Sciences of the United States of America 96(16): 9363-7.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  The origin of the H5N1 influenza viruses that killed six of eighteen infected humans in 1997 and were highly pathogenic in chickens has not been resolved. These H5N1 viruses transmitted directly to humans from infected poultry. In the poultry markets in Hong Kong, both H5N1 and H9N2 influenza viruses were cocirculating, raising the possibility of genetic reassortment. Here we analyze the antigenic and genetic features of H9N2 influenza viruses with different epidemiological backgrounds. The results suggest that the H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages. Among the chicken H9N2 viruses, six of the gene segments were apparently derived from an earlier chicken H9N2 virus isolated in China, whereas the PB1 and PB2 genes are closely related to those of the H5N1 viruses and a quail H9N2 virus-A/quail/Hong Kong/G1/97 (Qa/HK/G1/97)-suggesting that many of the 1997 chicken H9 isolates in the markets were reassortants. The similarity of the internal genes of Qa/HK/G1/97 virus to those of the H5N1 influenza viruses suggests that the quail virus may have been the internal gene donor. Our findings indicate that the human and poultry H5N1 influenza viruses in Hong Kong in 1997 were reassortants that obtained internal gene segments from Qa/HK/G1/97. However, we cannot be certain whether the replicate complex of H5N1 originated from Qa/HK/G1/97 or whether the reverse transfer occurred; the available evidence supports the former proposal.

            Descriptors:  genes viral, influenza epidemiology, influenza veterinary, influenza A virus avian classification, influenza A virus avian genetics, influenza A virus human classification, influenza A virus human genetics, poultry diseases epidemiology, chick embryo, chickens, coturnix, ducks, feces virology, Hong Kong epidemiology, influenza virology, influenza A virus avian pathogenicity, molecular sequence data, phylogeny, pigeons, poultry diseases virology.

Guo, Y., J. Li, and X. Cheng (1999). [Discovery of men infected by avian influenza A (H9N2) virus]. 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(2): 105-8.  ISSN: 1003-9279.

            Abstract:  OBJECTIVE: To understand whether the avian influenza A(H9N2) virus can infect men or not. METHODS: Seroepidemiological surveys for avian (H9N2) virus in human, chickens and pigs were conducted. The specimens for viral isolation were taken from throat of patients with influenza like disease, as well as from chickens, then the specimens were inoculated into embryonated chicken eggs. Afterward, the idsolates were identified with HI and NI tests. Meanwhile, the patients who would be studied individually were found to carry H9N2 virus. RESULTS: Approximately 19% of human had antibody to H9N2 virus with HI titers > or = 20, 5 strains of influenza A (H9N2) virus were isolated from the patients. CONCLUSION: Avian influenza A(H9N2) virus can infect men.

            Descriptors:  antibodies, viral blood, influenza virology, influenza A virus avian pathogenicity, China epidemiology, influenza epidemiology, influenza A virus avian classification, influenza A virus avian isolation and purification, seroepidemiologic studies.

Guo, Y., M. Wang, Y. Kawaoka, O. Gorman, T. Ito, T. Saito, and R.G. Webster (1992). Characterization of a new avian-like influenza A virus from horses in China. Virology 188(1): 245-55.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  In March 1989 a severe outbreak of respiratory disease occurred in horses in the Jilin and Heilongjiang provinces of Northeast China that caused up to 20% mortality in some herds. An influenza virus of the H3N8 subtype was isolated from the infected animals and was antigenically and molecularly distinguishable from the equine 2 (H3N8) viruses currently circulating in the world. The reference strain A/Equine/Jilin/1/89 (H3N8) was most closely related to avian H3N8 influenza viruses. Sequence comparisons of the entire hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix (M), and NS genes along with partial sequences of the three polymerase (PB1, PB2, PA) genes suggest that six of the eight gene segments (PA, HA, NP, NA, M, NS) are closely related to avian influenza viruses. Since direct sequence analysis can only provide a crude measure of relationship, phylogenetic analysis was done on the sequence information. Phylogenetic analyses of the entire HA, NP, M, and NS genes and of partial sequences of PB1, PB2, and PA indicated that these genes are of recent avian origin. The NP gene segment is closely related to the gene segment found in the newly described H14 subtype isolated from ducks in the USSR. The A/Equine/Jilin/1/89 (H3N8) influenza virus failed to replicate in ducks, but did replicate and cause disease in mice on initial inoculation and on subsequent passaging caused 100% mortality. In ferrets, the virus caused severe influenza symptoms. A second outbreak of influenza in horses in Northeast China occurred in April 1990 in the Heilongjiang province with 48% morbidity and no mortality. The viruses isolated from this outbreak were antigenically indistinguishable from those in the 1989 outbreak and it is probable that the reduced mortality was due to the immune status of of the horses in the region. No influenza was detected in horses in Northern China in the spring, summer, or fall of 1991 and no influenza has been detected in horses in adjacent areas. Our analysis suggests that this new equine influenza virus in horses in Northeast China is the latest influenza virus in mammals to emerge from the avian gene pool in nature and that it may have spread to horses without reassortment. The appearance of this new equine virus in China emphasizes the potential for whole avian influenza viruses to successfully enter mammalian hosts and serves as a model and a warning for the appearance of new pandemic influenza viruses in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

            Descriptors:  horse diseases microbiology, influenza A virus isolation and purification, orthomyxoviridae infections veterinary, antigens, viral genetics, antigens, viral immunology, base composition, chick embryo, China epidemiology, cloning, molecular, genes viral, horse diseases epidemiology, horses, influenza A virus avian immunology, influenza A virus genetics, influenza A virus immunology, influenza A virus pathogenicity, orthomyxoviridae infections epidemiology, orthomyxoviridae infections microbiology, phylogeny, species specificity, virus replication.

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.J., S. Krauss, D.A. Senne, I.P. Mo, K.S. Lo, X.P. Xiong, M. Norwood, K.F. Shortridge, R.G. Webster, and Y. Guan (2000). Characterization of the pathogenicity of members of the newly established H9N2 influenza virus lineages in Asia. Virology 267(2): 279-88.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The reported transmission of avian H9N2 influenza viruses to humans and the isolation of these viruses from Hong Kong poultry markets lend urgency to studies of their ecology and pathogenicity. We found that H9N2 viruses from North America differ from those of Asia. The North American viruses, which infect primarily domestic turkeys, replicated poorly in inoculated chickens. Phylogenetic analysis of the hemagglutinin and nucleoprotein genes indicated that the Asian H9N2 influenza viruses could be divided into three sublineages. Initial biological characterization of at least one virus from each lineage was done in animals. Early isolates of one lineage (A/Chicken/Beijing/1/94, H9N2) caused as high as 80% mortality rates in inoculated chickens, whereas all other strains were nonpathogenic. Sequence analysis showed that some isolates, including the pathogenic isolate, had one additional basic amino acid (A-R/K-S-S-R-) at the hemagglutinin cleavage site. Later isolates of the same lineage (A/Chicken/Hong Kong/G9/97, H9N2) that contains the PB1 and PB2 genes similar to Hong Kong/97 H5N1 viruses replicated in chickens, ducks, mice, and pigs but were pathogenic only in mice. A/Quail/Hong Kong/G1/97 (H9N2), from a second lineage that possesses the replicative complex similar to Hong Kong/97 H5N1 virus, replicated in chickens and ducks without producing disease signs, was pathogenic in mice, and spread to the brain without adaptation. Examples of the third Asian H9N2 sublineage (A/Chicken/Korea/323/96, Duck/Hong Kong/Y439/97) replicated in chickens, ducks, and mice without producing disease signs. The available evidence supports the notion of differences in pathogenicity of H9N2 viruses in the different lineages and suggests that viruses possessing genome segments similar to 1997 H5N1-like viruses are potentially pathogenic in mammals. Copyright 2000 Academic Press.

            Descriptors:  influenza A virus avian genetics, influenza A virus avian pathogenicity, binding sites genetics, chickens virology, DNA complementary chemistry, DNA complementary genetics, glycosylation, hemagglutinins viral genetics, hemagglutinins viral metabolism, Hong Kong epidemiology, mice, mice inbred BALB c virology, molecular sequence data, phylogeny, poultry diseases epidemiology, RNA viral genetics, reverse transcriptase polymerase chain reaction, sequence analysis, DNA, virulence genetics, virus replication.

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 (2003). X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus. Virology 309(2): 209-218.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  We have determined the structure of the HA of an avian influenza virus, A/duck/Ukraine/63, a member of the same antigenic subtype, H3, as the virus that caused the 1968 Hong Kong influenza pandemic, and a possible progenitor of the pandemic virus. We find that structurally significant differences between the avian and the human HAs are restricted to the receptor-binding site particularly the substitutions Q226L and G228S that cause the site to open and residues within it to rearrange, including the conserved residues, Y98, W153, and H183. We have also analyzed complexes formed by the HA with sialopentasaccharides in which the terminal sialic acid is in either alpha2,3- or alpha2,6-linkage to galactose. Comparing the structures of complexes in which an alpha2,3-linked receptor analog is bound to the H3 avian HA or to an H5 avian HA leads to the suggestion that all avian influenza HAs bind to their preferred alpha2,3-linked receptors similarly, with the analog in a trans conformation about the glycosidic linkage. We find that alpha2,6-linked analogs are bound by both human and avian HAs in a cis conformation, and that the incompatibility of an alpha2,6-linked receptor with the alpha2,3-linkage-specific H3 avian HA-binding site is partially resolved by a small change in the position and orientation of the sialic acid. We discuss our results in relation to the mechanism of transfer of influenza viruses between species.

            Descriptors:  biochemistry and molecular biophysics, virology, 1968 Hong Kong influenza pandemic.

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. (1974). Myxovirus-Hepatitis: Ein Modell. [A model of myxovirus hepatitis (infection of mice with avian influenza virus)]. Pathologia Et Microbiologia 40(3-4.)

            NAL Call Number:  448.8 Sch9

            Descriptors:  hepatitis, disease models, avian influenza virus, mice.

Hassler, D., T.F. Schwarz, and P. Kimmig (2003). Gefluegelpest: eine potenzielle Gefahr auch fuer Menschen.  [Avian influenza: Potential risk for humans.]. DMW Deutsche Medizinische Wochenschrift 128(27): 1467.  ISSN: 0012-0472.

            NAL Call Number:  448.8 D48

            Descriptors:  human medicine, infection, veterinary medicine, avian influenza, drug therapy, pathology, respiratory system disease, transmission, viral disease, coinfection, gene transfer, potential risk, prevention, recombination, zoonosis.

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.

Hatta, M., P. Halfmann, K. Wells, and Y. Kawaoka (2002). Human influenza a viral genes responsible for the restriction of its replication in duck intestine. Virology 295(2): 250-5.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  ducks virology, genes viral, influenza A virus human physiology, intestines virology,  viral proteins genetics, virus replication, cell line, DNA, complementary, avian genetics, avian metabolism, human genetics, human pathogenicity, RNA viral metabolism, recombination, genetic, transcription, genetic, viral proteins metabolism.

Hatta, M. and Y. Kawaoka (2002). The continued pandemic threat posed by avian influenza viruses in Hong Kong. Trends in Microbiology 10(7): 340-4.  ISSN: 0966-842X.

            NAL Call Number:  QR1.T74

            Abstract:  In 1997, a highly pathogenic avian H5N1 influenza virus was transmitted directly from live commercial poultry to humans in Hong Kong. Of the 18 people infected, six died. The molecular basis for the high virulence of this virus in mice was found to involve an amino acid change in the PB2 protein. To eliminate the source of the pathogenic virus, all birds in the Hong Kong markets were slaughtered. In 1999, another avian influenza virus of H9N2 subtype was transmitted to two children in Hong Kong. In 2000-2002, H5N1 avian viruses reappeared in the poultry markets of Hong Kong, although they have not infected humans. Continued circulation of H5N1 and other avian viruses in Hong Kong raises the possibility of future human influenza outbreaks. Moreover, the acquisition of properties of human viruses by the avian viruses currently circulating in southeast China might result in a pandemic.

            Descriptors:  communicable diseases, emerging virology, disease outbreaks, fowl plague virology, communicable diseases, emerging epidemiology, disease reservoirs, fowl plague epidemiology, Hong Kong epidemiology, influenza A virus avian genetics, avian pathogenicity, avian physiology, mice, virulence.

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, J. Geraci, P. Fiorelli, G. Early, and R.G. Webster (1986). Characterization of two influenza A viruses from a pilot whale. Journal of Virology 58(2): 655-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza A viruses of the H13N2 and H13N9 subtypes were isolated from the lung and hilar node of a pilot whale. Serological, molecular, and biological analyses indicate that the whale isolates are closely related to the H13 influenza viruses from gulls.

            Descriptors:  cetacea microbiology, influenza A virus isolation and purification, whales microbiology, antigens, viral immunology, ferrets microbiology, hemagglutinins viral immunology, influenza A virus avian analysis, influenza A virus analysis, influenza A virus immunology, influenza A virus physiology, lung microbiology, lymph nodes microbiology, neuraminidase immunology, nucleic acid hybridization, RNA viral analysis, virus replication.

Hinshaw, V.S., W.J. Bean, R.G. Webster, J.E. Rehg, P. Fiorelli, G. Early, J.R. Geraci, and D.J. St. Aubin (1984). Are seals frequently infected with avian influenza viruses? Journal of Virology 51(3): 863-5.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza A virus isolates of the H4N5 subtype (which has previously been detected only in birds) were recovered from harbor seals dying of viral pneumonia on the New England coast from June 1982 through March 1983. When these isolates were compared with other mammalian and avian viruses in serological assays and RNA-RNA competitive hybridization, it was found that the seal viruses were most closely related antigenically and genetically to recent avian virus strains and were readily distinguishable from mammalian viruses, including H7N7 isolates recovered from seals in 1980. Unlike any previous isolates from mammals, these recent seal viruses replicate in the intestinal tracts of ducks, a characteristic of avian viruses. The association of avian viruses with influenza outbreaks in seals suggests that transmission of avian viruses to seals is occurring in nature. Potentially, this may be an example of the adaptation of avian viruses to mammals, which would represent an intermediate step in the evolution of new mammalian strains.

            Descriptors:  animal diseases microbiology, fowl plague veterinary, influenza A virus avian pathogenicity, pinnipedia microbiology, seals microbiology, animal diseases mortality, fowl plague microbiology, fowl plague mortality, avian isolation and purification.

Hinshaw, V.S., R.G. Webster, B.C. Easterday, and W.J.J. Bean (1981). Replication of avian influenza A viruses in mammals. Infection and Immunity 34(2): 354-61.  ISSN: 0019-9567.

            NAL Call Number:  QR1.I57

            Abstract:  The recent appearance of an avian influenza A virus in seals suggests that viruses are transmitted from birds to mammals in nature. To examine this possibility, avian viruses of different antigenic subtypes were evaluated for their ability to replicate in three mammals-pigs, ferrets, and cats. In each of these mammals, avian strains replicated to high titers in the respiratory tract (10(5) to 10(7) 50% egg infective doses per ml of nasal wash), with peak titers at 2 to 4 days post-inoculation, similar to the pattern of human and other mammalian viruses in these animals. Most avian strains were recovered for 5 to 9 days post-inoculation. One avian H1N1 virus initially replicated poorly in pigs, but was adapted to this host and even transmitted to other pigs. Replication of the avian viruses occurred in the respiratory tracts of mammals, whereas, in birds, they replicate in the intestinal tract as well. The infected mammals had no significant disease signs and produced low levels of humoral antibodies; however, challenge experiments in ferrets indicated that they were immune. These studies suggest that influenza A viruses currently circulating in avian species represent a source of viruses capable of infecting mammals, thereby contributing to the influenza A antigenic pool from which new pandemic strains may originate.

            Descriptors:  Carnivora microbiology, cats microbiology, ferrets microbiology, influenza A virus avian growth and development, swine microbiology, adaptation, physiological, antibodies, viral biosynthesis, antigens, viral analysis, avian immunology, human growth and development, porcine growth and development, respiratory system microbiology, virus replication.

Hinshaw, V.S., R.G. Webster, C.W. Naeve, and B.R. Murphy (1983). Altered tissue tropism of human-avian reassortant influenza viruses. Virology 128(1): 260-3.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Avian influenza viruses replicate to high titers in the cells lining the intestinal tract of birds; however, human strains do not. A series of reassortant viruses with all six internal genes from an avian strain and one or both genes for the surface antigens from a human strain failed to transit and infect the intestinal tracts of ducks. However, these reassortants did replicate in the bursa of ducks after rectal inoculation. These studies provide the first evidence that the hemagglutinin and neuraminidase are critical for the enterotropism of avian viruses but are not essential for replication in other avian tissues.

            Descriptors:  hemagglutinins viral, influenza A virus avian physiology, human physiology, intestines microbiology, neuraminidase physiology, bursa of fabricius microbiology, ducks microbiology, genes viral, avian genetics, human genetics, recombination, genetic, virus replication.

Hiromoto, Y., T. Saito, S. Lindstrom, and K. Nerome (2000). Characterization of low virulent strains of highly pathogenic A/Hong Kong/156/97 (H5N1) virus in mice after passage in embryonated hens' eggs. Virology 272(2): 429-37.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian pathogenicity, ovum virology, cell line, chick embryo, clone cells, dogs, fowl plague mortality, avian growth and development, avian isolation and purification, mice, organ specificity, sequence analysis, DNA, sequence analysis, protein, serial passage, tropism, virulence, virus replication.

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.

Hoffmann, E., J. Stech, I. Leneva, S. Krauss, C. Scholtissek, P.S. Chin, M. Peiris, K.F. Shortridge, and R.G. Webster (2000). Characterization of the influenza A virus gene pool in avian species in southern China: was H6N1 a derivative or a precursor of H5N1? Journal of Virology 74(14): 6309-15.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In 1997, an H5N1 influenza virus outbreak occurred in chickens in Hong Kong, and the virus was transmitted directly to humans. Because there is limited information about the avian influenza virus reservoir in that region, we genetically characterized virus strains isolated in Hong Kong during the 1997 outbreak. We sequenced the gene segments of a heterogeneous group of viruses of seven different serotypes (H3N8, H4N8, H6N1, H6N9, H11N1, H11N9, and H11N8) isolated from various bird species. The phylogenetic relationships divided these viruses into several subgroups. An H6N1 virus isolated from teal (A/teal/Hong Kong/W312/97 [H6N1]) showed very high (>98%) nucleotide homology to the human influenza virus A/Hong Kong/156/97 (H5N1) in the six internal genes. The N1 neuraminidase sequence showed 97% nucleotide homology to that of the human H5N1 virus, and the N1 protein of both viruses had the same 19-amino-acid deletion in the stalk region. The deduced hemagglutinin amino acid sequence of the H6N1 virus was most similar to that of A/shearwater/Australia/1/72 (H6N5). The H6N1 virus is the first known isolate with seven H5N1-like segments and may have been the donor of the neuraminidase and the internal genes of the H5N1 viruses. The high homology between the internal genes of H9N2, H6N1, and the H5N1 isolates indicates that these subtypes are able to exchange their internal genes and are therefore a potential source of new pathogenic influenza virus strains. Our analysis suggests that surveillance for influenza A viruses should be conducted for wild aquatic birds as well as for poultry, pigs, and humans and that H6 isolates should be further characterized.

            Descriptors:  genome, viral, influenza A virus avian genetics, birds, China, fowl plague, hemagglutinin glycoproteins, influenza virus genetics, avian classification, avian isolation and purification, avian pathogenicity, human classification, human genetics, human isolation and purification, human pathogenicity, mice, mice inbred BALB c, neuraminidase genetics, phylogeny, polymerase chain reaction, sequence analysis, DNA.

Horimoto, T. and Y. Kawaoka (2001). Pandemic threat posed by avian influenza A viruses. Clinical Microbiology Reviews 14(1): 129-49.  ISSN: 0893-8512.

            NAL Call Number:  QR67.C54

            Abstract:  Influenza pandemics, defined as global outbreaks of the disease due to viruses with new antigenic subtypes, have exacted high death tolls from human populations. The last two pandemics were caused by hybrid viruses, or reassortants, that harbored a combination of avian and human viral genes. Avian influenza viruses are therefore key contributors to the emergence of human influenza pandemics. In 1997, an H5N1 influenza virus was directly transmitted from birds in live poultry markets in Hong Kong to humans. Eighteen people were infected in this outbreak, six of whom died. This avian virus exhibited high virulence in both avian and mammalian species, causing systemic infection in both chickens and mice. Subsequently, another avian virus with the H9N2 subtype was directly transmitted from birds to humans in Hong Kong. Interestingly, the genes encoding the internal proteins of the H9N2 virus are genetically highly related to those of the H5N1 virus, suggesting a unique property of these gene products. The identification of avian viruses in humans underscores the potential of these and similar strains to produce devastating influenza outbreaks in major population centers. Although highly pathogenic avian influenza viruses had been identified before the 1997 outbreak in Hong Kong, their devastating effects had been confined to poultry. With the Hong Kong outbreak, it became clear that the virulence potential of these viruses extended to humans.

            Descriptors:  disease outbreaks prevention and control, disease outbreaks veterinary, fowl plague epidemiology, influenza epidemiology, influenza A virus avian pathogenicity, adaptation, physiological, disease vectors, fowl plague transmission, Hong Kong epidemiology, influenza virology, avian classification, Mexico epidemiology, Pennsylvania epidemiology, poultry, viral proteins, virulence.

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.

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.

Itamura, S. (2004). [SARS, pandemic influenza, avian influenza: quest for missing link]. Tanpakushitsu Kakusan Koso; Protein, Nucleic Acid, Enzyme 49(6): 772-80.  ISSN: 0039-9450.

            NAL Call Number:  QD431.T3

            Descriptors:  influenza A virus, avian pathogenicity, SARS virus pathogenicity, severe acute respiratory syndrome virology, Asia epidemiology, disease outbreaks, avian influenza epidemiology, avian influenza transmission, avian influenza virology, poultry diseases epidemiology, poultry diseases transmission, poultry diseases virology, severe acute respiratory syndrome epidemiology, severe acute respiratory syndrome transmission, virulence, zoonoses epidemiology, zoonoses transmission.

Ito, T. (1999). Host range and pathogenicity of avian influenza virus: Animal surveilance of Hong Kong H5 virus. Journal of the Japanese Society of Poultry Diseases 35(1): 1-8.  ISSN: 0285-709X.

            Descriptors:  chickens, avian influenza virus, Newcastle disease virus, host parasite relations,  Hong Kong, Asia, birds, domestic animals, East Asia, Galliformes, influenza virus, livestock, orthomyxoviridae, paramyxoviridae, parasitism, poultry, useful animals, viruses.

Ito, T., J.N. Couceiro, S. Kelm, L.G. Baum, S. Krauss, M.R. Castrucci, I. Donatelli, H. Kida, J.C. Paulson, R.G. Webster, and Y. Kawaoka (1998). Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. Journal of Virology 72(9): 7367-73.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Genetic and biologic observations suggest that pigs may serve as "mixing vessels" for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.

            Descriptors:  hemagglutinin glycoproteins, influenza virus chemistry, influenza A virus avian metabolism, human metabolism, receptors, virus chemistry, adaptation, biological, amino acid sequence, amino acids, binding sites, ducks, hemagglutinin glycoproteins, influenza virus metabolism, avian classification, avian physiology, human classification, human physiology, molecular sequence data, phylogeny, receptors, virus metabolism, sequence homology, amino acid, swine, trachea virology.

Ito, T. (2003). Avian influenza and human health. Japanese Poultry Science 40(J2): J83-J88.  ISSN: 0029-0254.

            NAL Call Number:  41.8 V6446

            Abstract:  An H5N1 avian influenza A virus was directly transmitted from birds to humans in 1997-1998 in Hong Kong, infecting 18 humans, 6 of whom died. Epidemiological studies indicate that there has been no human-to-human transmission of the virus, suggesting that human cases in Hong Kong originated from independent transmission of the virus from birds. The H5N1 viruses isolated from humans have still displayed avian virus-like receptor specificity. This property is consistent with the fact that the virus did not establish within human populations. Subsequently, in March of 1999, another avian virus with the H9N2 subtype was isolated from two persons in Hong Kong. This virus also did not have the capacity for human-to-human spread. However, this case suggests that all subtypes of avian viruses (except H1 and H3 viruses) could be novel human influenza viruses with pandemic potential. It also supports the contention that intensive monitoring of bird populations should be an integral part of control policies for new human pandemic of influenza.

            Descriptors:  epidemiology, infection, avian influenza, epidemiology, infectious disease, respiratory system disease, transmission, viral disease, viral transmission.

Jameson, J., J. Cruz, M. Terajima, and F.A. Ennis (1999). Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species. Journal of Immunology 162(12): 7578-83.  ISSN: 0022-1767.

            NAL Call Number:  448.8 J8232

            Abstract:  Recently, an avian influenza A virus (A/Hong Kong/156/97, H5N1) was isolated from a young child who had a fatal influenza illness. All eight RNA segments were of avian origin. The H5 hemagglutinin is not recognized by neutralizing Abs present in humans as a result of infection with the human H1, H2, or H3 subtypes of influenza A viruses. Subsequently, five other deaths and several more human infections in Hong Kong were associated with this avian-derived virus. We investigated whether influenza A-specific human CD8+ and CD4+ T lymphocytes would recognize epitopes on influenza A virus strains derived from swine or avian species, including the 1997 H5N1 Hong Kong virus strains. Our results demonstrate that adults living in an urban area of the U.S. possess influenza A cross-serotype reactive CD8+ and CD4+ CTL that recognize multiple epitopes on influenza A viruses of other species. Bulk culture cytotoxicity was demonstrated against avian and human influenza A viruses. Enzyme-linked immunospot assays detected precursor CTL specific for both human CTL epitopes and the corresponding A/HK/97 viral sequences. We hypothesize that these cross-reactive CTL might provide partial protection to humans against novel influenza A virus strains introduced into humans from other species.

            Descriptors:  cd4 positive T lymphocytes immunology, CD4 positive T lymphocytes virology, CD8 positive T lymphocytes immunology, CD8 positive T lymphocytes virology, influenza A virus avian immunology, porcine immunology, cell line, chickens, cytotoxicity, immunologic genetics, ducks, enzyme linked immunosorbent assay, avian genetics, porcine genetics, leukocytes, mononuclear immunology, leukocytes, mononuclear virology, peptides genetics, peptides immunology, point mutation, stem cells immunology, stem cells virology, swine.

Jemmi, T., J. Danuser, and C. Griot (2000). Zoonosen als Risiko im Umgang mit Tieren und tierischen Produkten. [Zoonoses as a risk when associating with livestock or animal products]. Schweizer Archiv Fur Tierheilkunde 142(12): 665-71.  ISSN: 0036-7281.

            NAL Call Number:  41.8 Sch9

            Abstract:  The risk of zoonotic disease transmission when handling livestock or animal products is substantial. In industrialized countries, the classical zoonotic diseases such as tuberculosis or brucellosis are no longer in the foreground. Latent zoonoses such as salmonellosis and campylobacteriosis can cause serious disease in humans and have become a major public health problem during the past years. Since animals infected with these pathogens show only mild transient disease or no clinical signs at all, new concepts in the entire production line ("stable to table") are necessary in order to avoid human infection. Two emerging viruses with zoonotic potential--avian influenza virus and Nipah virus--have been found in Asia in 1997 and 1999. Both diseases had a major impact on disease control and public health in the countries of origin. In order to cope threats from infectious diseases, in particular those of public health relevance, a combined effort among all institutions involved will be necessary. The proposed "European Center for Infectious Diseases" and the "Swiss Center for Zoonotic Diseases" could be a potential approach in order to achieve this goal.

            Descriptors:  public health, infection, veterinary medicine, Campylobacteriosis, bacterial disease, Salmonellosis, animal product handling, livestock handling, meat inspection, foodborne zoonosis, food contamination prevention and control, food microbiology, meat microbiology, meat products microbiology, zoonoses transmission, animal husbandry, European Union, food handling, risk factors.

Jennings, L. (2004). Avian influenza: a public health risk for New Zealand. New Zealand Medical Journal 117(1192): U843.  ISSN: 1175-8716.

            NAL Call Number:  R99.N4

            Descriptors:  influenza, avian epidemiology, public health, communicable disease control methods, disease outbreaks statistics and numerical data, influenza A virus isolation and purification, avian influenza transmission, avian influenza virology, New Zealand epidemiology, poultry, risk factors, world health, zoonoses epidemiology, zoonoses transmission, zoonoses virology.

Jerabek, J. (2002). Chripka - ptaci, prasata, verejne zdravi. [Influenza - birds, swine, public health]. Veterinarstvi (Czech Republic) 52(3): 150-152.  ISSN: 0506-8231.

            NAL Call Number:  41.8 V6439

            Abstract:  This review article deals with influenza as a zoonosis. The pathogenicity of viruses, clinical symptoms, diagnosis and methods of transmission of the disease between different animal species and man are presented.

            Descriptors:  avian influenza virus, swine influenza virus, zoonoses, viroses, disease transmission, diagnosis, symptoms, ELISA, Europe, Asia, North America, America, immunoenzyme techniques, immunological techniques, infectious diseases, pathogenesis.

Joffe, H. and N.Y. Lee (2004). Social representation of a food risk: the Hong Kong avian bird flu epidemic. Journal of Health Psychology 9(4): 517-33.  ISSN: 1359-1053.

            Abstract:  The paper explores the social representation of the 2001 Hong Kong avian bird flu epidemic from the perspective of local women. Fifty women were asked to describe their first thoughts about the flu, and these were subsequently explored. Thematic analysis of the semi-structured interviews revealed that the first thoughts were characterized by: (a) the origin of the epidemic, (b) anchors for it, (c) emotions about it, and (d) images of it. Aspersion concerning the lack of hygiene of Mainland Chinese chicken rearers and chicken sellers in Hong Kong dominated the interviews. Other environmental factors were also stressed, as was regulation leniency and a drive to profit. Comparisons between old traditions and newer practices formed a central feature. The findings are discussed in terms of their continuity with western risk findings as well as their specific cultural nuances.

            Descriptors:  bird diseases epidemiology, food, social behavior, adult, bird diseases virology, culture, disease outbreaks, health behavior, Hong Kong epidemiology, hygiene, influenza A virus, avian isolation and purification, middle aged, questionnaires.

John, T.J. (2004). Avian influenza: expect the best but prepare for the worst. Indian Journal of Medical Research 119(2): iii-iv.  ISSN: 0971-5916.

            Descriptors:  birds virology, disease outbreaks prevention and control, influenza A virus, avian genetics, avian influenza transmission, India, avian influenza pathogenicity, avian influenza diagnosis.

Jou, W.M., M. Verhoeyen, R. Devos, E. Saman, R. Fang, D. Huylebroeck, W. Fiers, G. Threlfall, C. Barber, N. Carey, and S. Emtage (1980). Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA. Cell 19(3): 683-96.  ISSN: 0092-8674.

            NAL Call Number:  QH573.C42

            Abstract:  The complete sequence of a hemagglutinin (HA) gene of a recent human influenza A strain, A/Victoria/3/75, is 1768 nucleotides long and contains the information for 567 amino acids. It codes for a signal peptide of 16 amino acids, the HA1 chain of the mature hemagglutinin of 329 amino acids, a connecting region between HA1 and HA2 consisting of a single arginine residue and the HA2 portion of 221 amiino acids. The sequence is compared with the hemagglutinin of two members of other subtypes, the human H2 strain A/Jap/305/57 and the avian Hav1 strain A/FPV/Rostock/34, and with one of the same H3 subtype, A/Memphis/3/72. To align the HA1 chain of different major subtypes several deletions/insertions of single amino acids must be invoked, but two more extensive differences are found at both ends, one leading to an extension of the amino terminal sequence of HA1 and the other (four residues) occurring in the region processed away between HA1 and HA2. Comparison of the HA1 of two H3 strains suggests that drift probably depends on single base mutations, some of which change antigenic determinants. The HA2 region, which apparently is not involved in the immune response, is highly conserved even between different subtypes, and single base substitutions account for all the observed diversity. A hydrophobic segment of 24 residues is present in the same position close to the carboxyl terminus of HA2 in both Victoria and FPV, and presumably functions in implantation into the lipid bilayer. The many conserved features not only in HA2 but also in HA1 suggest a rather rigid architecture for the whole hemagglutinin molecule.

            Descriptors:  genes viral, hemagglutinins viral genetics, influenza A virus human genetics, RNA viral genetics, amino acid sequence, base sequence, carbohydrates analysis, cloning, molecular, codon, DNA, viral genetics, epitopes, hemagglutinins viral analysis, avian genetics.

Kaiser, J. (2004). Influenza: girding for disaster. Facing down pandemic flu, the world's defenses are weak. Science 306(5695): 394-7.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Descriptors:  antiviral agents therapeutic use, disease outbreaks prevention and control, influenza prevention and control, influenza vaccines supply and distribution, world health, adjuvants, immunologic, antiviral agents supply and distribution, clinical trials, developed countries, developing countries, influenza epidemiology, influenza A virus, avian immunology, avian pathogenicity, orthomyxoviridae immunology, orthomyxoviridae pathogenicity, patents, United States, vaccines, synthetic.

Kanegae, Y., S. Sugita, K.F. Shortridge, Y. Yoshioka, and K. Nerome (1994). Origin and evolutionary pathways of the H1 hemagglutinin gene of avian, swine and human influenza viruses: cocirculation of two distinct lineages of swine virus. Archives of Virology 134(1-2): 17-28.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The nucleotide sequences of the HA1 domain of the H1 hemagglutinin genes of A/duck/Hong Kong/36/76, A/duck/Hong Kong/196/77, A/sw/North Ireland/38, A/sw/Cambridge/39 and A/Yamagata/120/86 viruses were determined, and their evolutionary relationships were compared with those of previously sequenced hemagglutinin (H1) genes from avian, swine and human influenza viruses. A pairwise comparison of the nucleotide sequences revealed that the genes can be segregated into three groups, the avian, swine and human virus groups. With the exception of two swine strains isolated in the 1930s, a high degree of nucleotide sequence homology exists within the group. Two phylogenetic trees constructed from the substitutions at the synonymous site and the third codon position showed that the H1 hemagglutinin genes can be divided into three host-specific lineages. Examination of 21 hemagglutinin genes from the human and swine viruses revealed that two distinct lineages are present in the swine population. The swine strains, sw/North Ireland/38 and sw/Cambridge/39, are clearly on the human lineage, suggesting that they originate from a human A/WSN/33-like variant. However, the classic swine strain, sw/Iowa/15/30, and the contemporary human viruses are not direct descendants of the 1918 human pandemic strain, but did diverge from a common ancestral virus around 1905. Furthermore, previous to this the above mammalian viruses diverged from the lineage containing the avian viruses at about 1880.

            Descriptors:  evolution, hemagglutinins viral genetics, influenza A virus avian genetics, human genetics, porcine genetics, amino acid sequence, chick embryo, genes viral, hemagglutinin glycoproteins, influenza virus, avian classification, human classification, porcine classification, molecular sequence data, phylogeny, sequence homology, amino acid.

Kaplan, M.M. (1980). Some epidemiological and virological relationships between human and animal influenza. Comparative Immunology, Microbiology and Infectious Diseases 3(1-2): 19-24.  ISSN: 0147-9571.

            NAL Call Number:  QR180.C62

            Descriptors:  disease reservoirs, influenza microbiology, influenza A virus genetics, orthomyxoviridae infections veterinary, genes viral, horses microbiology, influenza A virus avian, influenza A virus, porcine, orthomyxoviridae infections microbiology, orthomyxoviridae infections transmission, recombination, genetic.

Karasin, A.I., I.H. Brown, S. Carman, and C.W. Olsen (2000). Isolation and characterization of H4N6 avian influenza viruses from pigs with pneumonia in Canada.  Journal of Virology 74(19): 9322-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In October 1999, H4N6 influenza A viruses were isolated from pigs with pneumonia on a commercial swine farm in Canada. Phylogenetic analyses of the sequences of all eight viral RNA segments demonstrated that these are wholly avian influenza viruses of the North American lineage. To our knowledge, this is the first report of interspecies transmission of an avian H4 influenza virus to domestic pigs under natural conditions.

            Descriptors:  influenza A virus avian isolation and purification, pneumonia, viral virology, swine diseases virology, Canada epidemiology, influenza A virus avian genetics, molecular sequence data, phylogeny, pneumonia, viral epidemiology, swine, swine diseases epidemiology.

Karasin, A.I., C.W. Olsen, I.H. Brown, S. Carman, M. Stalker, and G. Josephson (2000). H4N6 influenza virus isolated from pigs in Ontario. Canadian Veterinary Journal Revue Veterinaire Canadienne  41(12): 938-9.  ISSN: 0008-5286.

            NAL Call Number:  41.8 R3224

            Descriptors:  influenza A virus avian isolation and purification, swine diseases virology, antigens, viral analysis, enzyme linked immunosorbent assay veterinary, incidence, avian immunology, Ontario epidemiology, swine, swine diseases epidemiology, swine diseases immunology.

Karasin, A.I., M.M. Schutten, L.A. Cooper, C.B. Smith, K. Subbarao, G.A. Anderson, S. Carman, and C.W. Olsen (2000). Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977-1999: evidence for wholly human and reassortant virus genotypes. Virus Research 68(1): 71-85.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Since 1998, H3N2 viruses have caused epizootics of respiratory disease in pigs throughout the major swine production regions of the U.S. These outbreaks are remarkable because swine influenza in North America had previously been caused almost exclusively by H1N1 viruses. We sequenced the full-length protein coding regions of all eight RNA segments from four H3N2 viruses that we isolated from pigs in the Midwestern U.S. between March 1998 and March 1999, as well as from H3N2 viruses recovered from a piglet in Canada in January 1997 and from a pig in Colorado in 1977. Phylogenetic analyses demonstrated that the 1977 Colorado and 1997 Ontario isolates are wholly human influenza viruses. However, the viruses isolated since 1998 from pigs in the Midwestern U.S. are reassortant viruses containing hemagglutinin, neuraminidase and PB1 polymerase genes from human influenza viruses, matrix, non-structural and nucleoprotein genes from classical swine viruses, and PA and PB2 polymerase genes from avian viruses. The HA proteins of the Midwestern reassortant swine viruses can be differentiated from those of the 1995 lineage of human H3 viruses by 12 amino acid mutations in HA1. In contrast, the Sw/ONT/97 virus, which did not spread from pig-to-pig, lacks 11 of these changes.

            Descriptors:  influenza A virus avian genetics, human genetics, porcine classification, porcine genetics, reassortant viruses genetics, genotype, influenza veterinary, influenza virology, molecular sequence data, North America, phylogeny, swine, swine diseases virology.

Katz, J.M. (2003). The impact of avian influenza viruses on public health. Avian Diseases 47(Special Issue): 914-920.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  In the late 1990s, H5N1 and H9N2 avian influenza viruses caused respiratory infections in humans in Hong Kong. Exposure to domestic poultry in live-bird markets was significantly associated with human H5N1 disease. Seroepidemiologic studies conducted among contacts of H5N1-infected persons determined that human-to-human transmission of the avian H5N1 viruses occurred but was rare. The relatively high rates of H5 and H9 antibody seroprevalence among Hong Kong poultry workers in 1997 highlight the potential for avian viruses to transmit to humans, particularly those with occupational exposure. Such transmission increases the likelihood of reassortment between a currently circulating human virus and an avian virus and thus the creation of a strain with pandemic potential.

            Descriptors:  epidemiology, immune system, infection, respiratory infection, infectious disease, respiratory system disease, antibody seroprevalence, live bird markets, pandemic, potential public health, viral transmission.

Katz, J.M., W. Lim, C.B. Bridges, T. Rowe, J. Hu Primmer, X. Lu, R.A. Abernathy, M. Clarke, L. Conn, H. Kwong, M. Lee, G. Au, Y.Y. Ho, K.H. Mak, N.J. Cox, and K. Fukuda (1999). Antibody response in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts. Journal of Infectious Diseases 180(6): 1763-70.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  The first documented outbreak of human respiratory disease caused by avian influenza A (H5N1) viruses occurred in Hong Kong in 1997. The kinetics of the antibody response to the avian virus in H5N1-infected persons was similar to that of a primary response to human influenza A viruses; serum neutralizing antibody was detected, in general, >/=14 days after symptom onset. Cohort studies were conducted to assess the risk of human-to-human transmission of the virus. By use of a combination of serologic assays, 6 of 51 household contacts, 1 of 26 tour group members, and none of 47 coworkers exposed to H5N1-infected persons were positive for H5 antibody. One H5 antibody-positive household contact, with no history of poultry exposure, provided evidence that human-to-human transmission of the avian virus may have occurred through close physical contact with H5N1-infected patients. In contrast, social exposure to case patients was not associated with H5N1 infection.

            Descriptors:  antibodies, viral blood, hemagglutinin glycoproteins, influenza virus immunology, influenza immunology, influenza transmission, influenza A virus avian immunology, adolescent, adult, child, child, preschool, cohort studies, family health, infant, influenza virology, avian isolation and purification, interpersonal relations, middle aged, neutralization tests, poultry virology.

Katz, J.M., X. Lu, A.M. Frace, T. Morken, S.R. Zaki, and T.M. Tumpey (2000). Pathogenesis of and immunity to avian influenza A H5 viruses. Biomedicine and Pharmacotherapy Biomedecine and Pharmacotherapie 54(4): 178-87.  ISSN: 0753-3322.

            NAL Call Number:  R41.B52

            Abstract:  In 1997 in Hong Kong, 18 human cases of respiratory illness were caused by an avian influenza A H5N1 virus. Although avian influenza viruses had not previously been known to cause respiratory illness in humans, the H5N1 viruses caused severe illness and death, primarily in individuals aged > 12 years. The introduction of H5N1 viruses into humans raised concerns about the potential of these viruses to cause a pandemic. We have used the BALB/c mouse to better understand the pathogenesis of and immunity to the H5N1 viruses in a mammalian model. Previously, we demonstrated that H5N1 viruses isolated from humans replicated efficiently in the lungs of mice without prior adaptation to this host. Two general phenotypes of pathogenicity of H5N1 viruses, based on high and low lethality for mice, were observed. We now demonstrate that in addition to a lethal outcome, H5N1 viruses with a high pathogenicity phenotype exhibit additional features that include rapid and uncontrolled replication in the lungs of infected mice, dissemination and replication of the virus in other organs, and depletion of peripheral blood leukocytes. The BALB/c mouse model was also used to better understand the parameters of protective immunity to the H5N1 viruses. Prior infection with H5N1 viruses of low pathogenicity or an antigenically related non-pathogenic H5N3 virus protected mice from death by infection with a highly pathogenic HK/483 virus. Serum hemagglutination-inhibition antibody titers of 40 or greater were associated with protection of mice from death. Immunization of mice with baculovirus-expressed recombinant H5 hemagglutinin protein or a previously defined HS-specific synthetic peptide induced MHC class II restricted CTL activity. Mice that had CTL activity but no serum hemagglutination-inhibition antibody were not protected from a lethal challenge with H5N1 virus. These results suggest that antibody is required for protection of mice against lethal challenge with H5N1 viruses of the high pathogenicity phenotype.

            Descriptors:  influenza A virus avian immunology, avian pathogenicity, antibodies, viral blood, antigens, viral analysis, immunization, influenza virology, influenza vaccine immunology, mice, mice inbred BALB c, T lymphocytes, cytotoxic immunology, virus replication.

Katz, J.M., X. Lu, T.M. Tumpey, C.B. Smith, M.W. Shaw, and K. Subbarao (2000). Molecular correlates of influenza A H5N1 virus pathogenesis in mice. Journal of Virology 74(22): 10807-10.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Highly pathogenic avian influenza A H5N1 viruses caused an outbreak of human respiratory illness in Hong Kong. Of 15 human H5N1 isolates characterized, nine displayed a high-, five a low-, and one an intermediate-pathogenicity phenotype in the BALB/c mouse model. Sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice. Alone or in combination, these specific residues are the likely determinants of virulence of human H5N1 influenza viruses in this model.

            Descriptors:  influenza virology, influenza A virus avian genetics, avian pathogenicity, adolescent, adult, child, preschool, disease models, animal, infant, influenza physiopathology, avian classification, mice, mice inbred BALB c, middle aged, molecular sequence data, phenotype, sequence analysis, DNA, viral proteins genetics, virulence.

Kaverin, N.V., I.A. Rudneva, Y.A. Smirnov, and N.N. Finskaya (1988). Human-avian influenza virus reassortants: effect of reassortment pattern on multi-cycle reproduction in MDCK cells. Archives of Virology 103(1-2): 117-26.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Human-avian influenza reassortants possessing the HA gene of the avian parent virus were tested for their ability to replicate in MDCK cells at 37 degrees C and 31 degrees C. Both avian parent viruses, A/Duck/Ukraine/1/63 (H3N8) and A/Duck/Hoshimin/014/78 (H5N3) induced an efficient multi-cycle infection at 37 degrees C, but replicated poorly at 31 degrees C, whereas the human parent virus, MDCK-adapted variant of A/USSR/90/77 (H1N1) strain, replicated efficiently at both temperatures. The reassortant clone possessing the HA gene of A/Duck/Ukraine/1/63 virus and the other 7 genes of A/USSR/90/77 virus replicated at both temperatures almost as efficiently as the human parent virus. Among the reassortants between A/Duck/Hoshimin/014/78 and A/USSR/90/77, the clones possessing the HA and NA genes of the avian strain, or the HA, NA, NP, and NS genes of the avian strain, and the other genes of the human parent virus, replicated poorly at both temperatures, especially at 31 degrees C, whereas the reassortant possessing the HA, NA, and M genes of the avian virus replicated at both temperatures fairly efficiently. The results are discussed in connection with the limitations imposed by different genes upon avian influenza viruses' ability to replicate in mammalian cells.

            Descriptors:  genes viral, hemagglutinins viral physiology, influenza A virus avian pathogenicity, human pathogenicity, virus replication, birds microbiology, chick embryo, hemagglutinins viral biosynthesis, hemagglutinins viral genetics, avian genetics, human genetics, RNA viral analysis, temperature, transfection, viral proteins biosynthesis.

Kaverin, N.V., Y.A. Smirnov, E.A. Govorkova, I.A. Rudneva, A.K. Gitelman, A.S. Lipatov, N.L. Varich, S.S. Yamnikova, N.V. Makarova, R.G. Webster, and D.K. Lvov (2000). Cross-protection and reassortment studies with avian H2 influenza viruses. Archives of Virology 145(6): 1059-66.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  In order to assess the degree of immune cross-protection among avian H2 influenza virus strains, mice were immunised with beta-propiolactone-inactivated virus preparations and infected intranasally with mouse-adapted variant of A/Black Duck/New Jersey/1580/78 (H2N3) strain. The experiments with 11 avian H2 strains revealed that both Eurasian and American H2 avian influenza viruses exhibit either high or moderate degree of cross-protection. The grouping of the strains in accordance with their cross-protection efficiency does not coincide with H2 phylogenetic branches. Several reassortant clones were obtained with the use of A/Pintail Duck/Primorie/695/76 (H2N3) strain and high-yield X-67 reassortant as parent viruses, among them a high-yield H2N3 reassortant. Taking into account the data on cross-protection among avian H2 strains, the high-yield H2N3 reassortant may be regarded as a prototype strain to be used for the preparation of killed vaccines in the case of a new appearance of avian H2 haemagglutinin in circulation in humans.

            Descriptors:  influenza prevention and control, influenza A virus avian genetics, avian immunology, influenza vaccine immunology, reassortant viruses immunology, chick embryo, cross reactions, immunization, influenza immunology, avian pathogenicity, mice, reassortant viruses genetics, vaccines, attenuated immunology.

Kaverin, N.V. and Y.A. Smirnov (2003). An interspecies transmission of influenza A viruses and pandemics. Voprosy Virusologii 48(3): 4-10.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Molecular and genetic data are summarized on the origin of influenza A virus pandemic variants. Conceptual modifications of the reassortment theory of the origin of pandemic strains are discussed in connection with the appearance of new H5 and H9 avian influenza viruses, which caused the respiratory infection in man and which are presently in the focus of attention as possible agents of future pandemic.

            Descriptors:  epidemiology, infection, respiratory system, veterinary medicine, influenza A, respiratory system disease, viral disease, pandemic, strain origins, reassortment theory.

Kawaoka, Y. (1991). Difference in replication and pathogenicity of influenza A viruses in chickens and mice. Journal of Veterinary Medical Science the Japanese Society of Veterinary Science 53(1): 125-6.  ISSN: 0916-7250.

            NAL Call Number:  SF604.J342

            Descriptors:  chickens microbiology, influenza A virus avian physiology, porcine physiology, influenza A virus physiology, mice microbiology, cloaca microbiology, avian pathogenicity, porcine pathogenicity, influenza A virus pathogenicity, orthomyxoviridae infections microbiology, orthomyxoviridae infections veterinary, poultry diseases microbiology, rodent diseases microbiology, trachea microbiology, virus replication.

Kawaoka, Y., E. Bordwell, and R.G. Webster (1987). Intestinal replication of influenza A viruses in two mammalian species. Brief report. Archives of Virology 93(3-4): 303-8.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The sites of replication of influenza A viruses in ferrets and pigs were studied. The majority of the swine, equine, and avian influenza A viruses tested were recovered from the intestinal tract of ferrets as well as from the respiratory tract; most of the human influenza viruses studied were recovered only from the respiratory tract. In contrast with ferrets, only Hong Kong/1/68 (H 3 N 2) influenza virus was recovered from the intestinal tract of pigs. Despite the large biological variability found in ferrets and in pigs, the results do establish that the majority of influenza viruses have the potential to replicate in the intestinal tissues of some mammals. Additionally, the study suggests that there are differences among the influenza A viruses in tissue tropism in different mammals. Both viral and host genetic factors determine the tissue tropism of influenza viruses in mammals.

            Descriptors:  influenza A virus physiology, intestines microbiology, virus replication, ferrets, avian physiology, human physiology, porcine physiology, swine.

Kawaoka, Y., S. Krauss, and R.G. Webster (1989). Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. Journal of Virology 63(11): 4603-8.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  We determined the origin and evolutionary pathways of the PB1 genes of influenza A viruses responsible for the 1957 and 1968 human pandemics and obtained information on the variable or conserved region of the PB1 protein. The evolutionary tree constructed from nucleotide sequences suggested the following: (i) the PB1 gene of the 1957 human pandemic strain, A/Singapore/1/57 (H2N2), was probably introduced from avian species and was maintained in humans until 1968; (ii) in the 1968 pandemic strain, A/NT/60/68 (H3N2), the PB1 gene was not derived from the previously circulating virus in humans but probably from another avian virus; and (iii) a current human H3N2 virus inherited the PB1 gene from an A/NT/60/68-like virus. Nucleotide sequence analysis also showed that the avian PB1 gene was introduced into pigs. Hence, transmission of the PB1 gene from avian to mammalian species is a relatively frequent event. Comparative analysis of deduced amino acid sequences disclosed highly conserved regions in PB1 proteins, which may be key structures required for PB1 activities.

            Descriptors:  evolution, genes, structural, viral, influenza transmission, influenza A virus avian genetics, human genetics, viral proteins genetics, amino acid sequence, cloning, molecular, influenza epidemiology, porcine genetics, molecular sequence data, sequence homology, nucleic acid, species specificity, swine.

Kaye, D. and C.R. Pringle (2005). Avian influenza viruses and their implication for human health. Clinical Infectious Diseases 40(1): 108-12.  ISSN: 1537-6591.

            NAL Call Number:  RC111.R4

            Abstract:  Widespread outbreaks of avian influenza in domestic fowl throughout eastern Asia have reawakened concern that avian influenza viruses may again cross species barriers to infect the human population and thereby initiate a new influenza pandemic. Simultaneous infection of humans (or swine) by avian influenza viruses in the presence of human influenza viruses could theoretically generate novel influenza viruses with pandemic potential as a result of reassortment of genome subunits between avian and mammalian influenza viruses. These hybrid viruses would have the potential to express surface antigens from avian viruses to which the human population has no preexisting immunity. This article reviews current knowledge of the routes of transmission of avian influenza A viruses to humans, places the risk of appearance of a new pandemic influenza virus in perspective, and describes the recently observed epidemiology and clinical syndromes of avian influenza in humans.

            Descriptors:  influenza A virus, viral diseases, zoonoses, birds, human, avian influenza virus.

Keawcharoen, J., K. Oraveerakul, T. Kuiken, R.A. Fouchier, A. Amonsin, S. Payungporn, S. Noppornpanth, S. Wattanodorn, A. Theambooniers, R. Tantilertcharoen, R. Pattanarangsan, N. Arya, P. Ratanakorn, D.M. Osterhaus, and Y. Poovorawan (2004). Avian influenza H5N1 in tigers and leopards. Emerging Infectious Diseases 10(12): 2189-91.  ISSN: 1080-6040.

            NAL Call Number:  RA648.5.E46

            Abstract:  Influenza virus is not known to affect wild felids. We demonstrate that avian influenza A (H5N1) virus caused severe pneumonia in tigers and leopards that fed on infected poultry carcasses. This finding extends the host range of influenza virus and has implications for influenza virus epidemiology and wildlife conservation.

            Descriptors:  zoo animals virology, influenza veterinary, influenza A virus, avian pathogenicity, Panthera virology, chickens virology, food microbiology, influenza virology, avian genetics, lung virology, meat virology, phylogeny, tigers virology, variation genetics.

Kelly, D.C. and N.J. Dimmock (1974). Fowl plaque virus replication in mammalian cell-avian erythrocyte heterokaryons: studies concerning the actinomycin D and ultra-violet light sensitive phase in influenza virus replication. Virology 61(1): 210-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  cell nucleus microbiology, dactinomycin pharmacology, influenza A virus avian growth and development, ultraviolet rays, virus replication drug effects, virus replication radiation effects, antigens, viral analysis, autoradiography, cell fusion, cell line, cell nucleus immunology, cultured cells cytology, chick embryo, chickens, erythrocytes cytology, fluorescent antibody technique, hamsters, hemagglutinins viral, avian immunology, avian metabolism, kidney, l cells cell line, mice, neuraminidase biosynthesis, nucleoproteins biosynthesis, radiation effects, viral proteins biosynthesis.

Kemink, S.A., R.A. Fouchier, F.W. Rozendaal, J.M. Broekman, M. Koopmans, A.D. Osterhaus, and P.M. Schneeberger (2004 ). Een fatale infectie door aviair influenza-A (H7N7)-virus en aanpassing van het preventiebeleid. [A fatal infection due to avian influenza-A (H7N7) virus and adjustment of the preventive measures]. Nederlands Tijdschrift Voor Geneeskunde 148(44): 2190-4.  ISSN: 0028-2162.

            Abstract:  In February 2003, the highly pathogenic avian influenza-A virus, subtype H7N7, was the causative agent of a large outbreak of fowl plague in the Netherlands. Two days after visiting a poultry farm that was infected by fowl plague, a 57-year-old male veterinarian developed malaise, headache and fever. After 8 days he was admitted to hospital with signs of pneumonia. Five days later, his condition deteriorated alarmingly. Despite extensive pharmacotherapy he died 4 days later of acute pneumonia. Influenza-A virus, subtype H7N7, was identified by means of reverse transcriptase/PCR in broncho-alveolar washings that had been obtained earlier; routine virus culture yielded the isolate A/Nederland/219/03, which differs by 14 amino-acid substitutions from the first isolate in a chicken (A/kip/Nederland/1/03). Partly as a result of this case, the preventive measures were then adjusted; people who came into contact with infected poultry were given increased possibilities for vaccination and the administration of oseltamivir.

            Descriptors:  influenza A virus, avian isolation and purification, avian influenza transmission, occupational diseases prevention and control, poultry diseases transmission, zoonoses, disease outbreaks, fatal outcome, avian influenza pathogenicity, avian influenza epidemiology, avian influenza prevention and control, avian influenza virology, middle aged, Netherlands epidemiology, occupational diseases virology, poultry, poultry diseases epidemiology, veterinarians.

Kida, H. (1997). [Ecology of influenza viruses in animals and the mechanism of emergence of new pandemic strains]. Nippon Rinsho Japanese Journal of Clinical Medicine 55(10): 2521-6.  ISSN: 0047-1852.

            Abstract:  Ecological studies on influenza viruses revealed that the hemagglutinin genes are introduced into new pandemic strains from viruses circulating in migratory ducks through domestic ducks and pigs in southern China. Experimental infection of pigs with 38 avian influenza virus strains with H1-H13 hemagglutinins showed that at least one strain of each HA subtype replicated in the upper respiratory tract of pigs. Co-infection of pigs with a swine virus and with an avian virus generated reassortant viruses. The results indicate that avian viruses of any subtype can contribute genes in the generation of reassortants. Virological surveillance revealed that influenza viruses in waterfowl reservoir are perpetuated year-by-year in the frozen lake water while ducks are absent.

            Descriptors:  influenza veterinary, bird diseases transmission, birds, horse diseases transmission,  horses, influenza transmission, swine, swine diseases transmission, zoonoses.

Kida, H., T. Ito, J. Yasuda, Y. Shimizu, C. Itakura, K.F. Shortridge, Y. Kawaoka, and R.G. Webster (1994). Potential for transmission of avian influenza viruses to pigs. Journal of General Virology 75(9):  2183-2188.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  Pandemic strains of influenza A virus arise by genetic reassortment between avian and human viruses. Pigs have been suggested to generate such reassortants as intermediate hosts. In order for pigs to serve as 'mixing vessels' in genetic reassortment events, they must be susceptible to both human and avian influenza viruses. The ability of avian influenza viruses to replicate in pigs, however, has not been examined comprehensively. In this study, we assessed the growth potential of 42 strains of influenza virus in pigs. Of these, 38 were avian strains, including 27 with non-human-type haemagglutinins (HA; H4 to H13). At least one strain of each HA subtype replicated in the respiratory tract of pigs for 5 to 7 days to a level equivalent to that of swine and human viruses. These results indicate that avian influenza viruses with or without non-human-type HAs can be transmitted to pigs, thus raising the possibility of introduction of their genes into humans. Sera from pigs infected with avian viruses showed high titres of antibodies in ELISA and neutralization tests, but did not inhibit haemagglutination of homologous viruses, cautioning against the use of haemagglutination-inhibition tests to identify pigs infected with avian influenza viruses. Co-infection of pigs with a swine virus and with an avian virus unable to replicate in this animal generated reassortant viruses, whose polymerase and HA genes were entirely of avian origin, that could be passaged in pigs. This finding indicates that even avian viruses that do not replicate in pigs can contribute genes in the generation of reassortants.

            Descriptors:  evolution and adaptation, genetics, immune system, infection, microbiology, vector biology, veterinary medicine, ELISA antibody hemagglutination inhibiting antibody mixing vessel neutralizing antibody pandemic strain origin reassortant virus generation swine virus avian virus co infection virus replication.

Klimov, A., Y. Ghendon, H. Zavadova, J. Broucek, and T. Medvedeva (1983). High reproduction capacity of recombinants between H3N2 human influenza and fowl plague viruses is due to the gene coding for M proteins. Acta Virologica 27(5): 434-8.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Recombinants between H3N2 human influenza viruses (A/Victoria/3/75 and A/Bangkok/1/79, low-yielding parents in chick embryos) and fowl plague virus (FPV, a high-yielding parent in chick embryos) have been obtained. The high reproductive capacity of recombinants in chick embryos has been shown to be due to the gene coding for M proteins.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, recombination, genetic, viral proteins genetics, virus replication, chick embryo, avian physiology, human physiology, viral matrix proteins.

Klingeborn, B., L. Englund, R. Rott, N. Juntti, and G. Rockborn (1985). An avian influenza A virus killing a mammalian species--the mink. Brief report. Archives of Virology 86(3-4): 347-51.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  During October of 1984 an influenza epidemic occurred on mink farms in the coastal region of South Sweden. Six strains of an influenza A virus were isolated. All six isolates were of the H 10 subtype in combination with N4. The H 10 subtype in combination with various N subtypes was hitherto only known to occur in avian strains, the prototype being the A/chicken/Germany/N/49 (H 10N7) virus.

            Descriptors:  disease outbreaks veterinary, influenza veterinary, influenza A virus avian pathogenicity, mink, influenza epidemiology.

Kodihalli, S., H. Goto, D.L. Kobasa, S. Krauss, Y. Kawaoka, and R.G. Webster (1999). DNA vaccine encoding hemagglutinin provides protective immunity against H5N1 influenza virus infection in mice. Journal of Virology 73(3): 2094-8.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and six deaths. Strategies must be developed to deal with this virus if it should reappear, and prospective vaccines must be developed to anticipate a future pandemic. We have determined that unadapted H5N1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological studies of lethal avian influenza virus infection. We report that a DNA vaccine encoding hemagglutinin from the index human influenza isolate A/HK/156/97 provides immunity against H5N1 infection of mice. This immunity was induced against both the homologous A/HK/156/97 (H5N1) virus, which has no glycosylation site at residue 154, and chicken isolate A/Ck/HK/258/97 (H5N1), which does have a glycosylation site at residue 154. The mouse model system should allow rapid evaluation of the vaccine's protective efficacy in a mammalian host. In our previous study using an avian model, DNA encoding hemagglutinin conferred protection against challenge with antigenic variants that differed from the primary antigen by 11 to 13% in the HA1 region. However, in our current study we found that a DNA vaccine encoding the hemagglutinin from A/Ty/Ir/1/83 (H5N8), which differs from A/HK/156/97 (H5N1) by 12% in HA1, prevented death but not H5N1 infection in mice. Therefore, a DNA vaccine made with a heterologous H5 strain did not prevent infection by H5N1 avian influenza viruses in mice but was useful in preventing death.

            Descriptors:  hemagglutinin glycoproteins, influenza virus immunology, influenza prevention and control, influenza A virus avian immunology, influenza vaccine immunology, vaccines, DNA immunology, antibodies, viral blood, hemagglutinin glycoproteins, influenza virus genetics, immunization, mice, mice inbred BALB c.

Kodihalli, S., D.L. Kobasa, and R.G. Webster (2000). Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines. Vaccine 18(23): 2592-9.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  The cross-species transfer of a H5N1 influenza virus from birds to humans, and the systemic spread of this virus in mice, has accelerated the efforts to devise protective strategies against lethal influenza viruses. DNA vaccination with the highly conserved nucleoprotein gene appears to provide cross protection against influenza A viruses in murine models. Whether such vaccines would protect human hosts against different influenza A viruses, including strains with pandemic potential, is unclear. Our aim in this study is to evaluate the ability of a combination DNA vaccine consisting of two plasmids encoding the HA genes from two different subtypes and a DNA vaccine encoding the viral nucleoprotein gene from a H5 virus to induce protection against highly lethal infection caused by H5 and H7 influenza viruses in chickens. Chickens given a single dose of plasmids expressing H5 and H7 hemagglutinins protected the birds from infection by either subtype. However, birds immunized with nucleoprotein DNA and challenged with either A/Ck/Vic/1/85(H7N7) or A/Ty/Ir/1/83 (H5N8) showed definite signs of infection, suggesting inadequate immunity against viral infection. Fifty percent of the nucleoprotein DNA immunized birds survived infection by influenza A/Ty/Ir/1/83 (H5N8) virus (virus of same subtype) while 42% survived infection by influenza A/Ck/Vic/1/85/(H7N7) virus (virus of a different subtype). These studies demonstrate that immunization with DNA encoding a type-specific gene may not be effective against either homologous or heterologous strains of virus, particularly if the challenge virus causes a highly lethal infection. However, the combination of HA subtype vaccines are effective against lethal infection caused by viruses expressing any of the HA subtypes used in the combination preparation.

            Descriptors:  chickens immunology, hemagglutinin glycoproteins, influenza virus immunology, influenza veterinary, influenza A virus avian immunology, influenza vaccine immunology, nucleoproteins, poultry diseases prevention and control, vaccination veterinary, vaccines, DNA immunology, viral core proteins immunology, cos cells, Cercopithecus aethiops, evaluation studies, hemagglutinin glycoproteins, influenza virus genetics, influenza immunology, influenza prevention and control, influenza transmission, avian genetics, mice, plasmids immunology, poultry diseases immunology, recombinant fusion proteins immunology, species specificity, transfection, viral core proteins genetics, zoonoses.

Koopmans, M., B. Wilbrink, M. Conyn, G. Natrop, H. van der Nat, H. Vennema, A. Meijer, J. van Steenbergen, R. Fouchier, A. Osterhaus, and A. Bosman (2004). Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet  363(9409): 587-93.  ISSN: 1474-547X.

            NAL Call Number:  448.8 L22

            Abstract:  BACKGROUND: An outbreak of highly pathogenic avian influenza A virus subtype H7N7 started at the end of February, 2003, in commercial poultry farms in the Netherlands. Although the risk of transmission of these viruses to humans was initially thought to be low, an outbreak investigation was launched to assess the extent of transmission of influenza A virus subtype H7N7 from chickens to humans. METHODS: All workers in poultry farms, poultry farmers, and their families were asked to report signs of conjunctivitis or influenza-like illness. People with complaints were tested for influenza virus type A subtype H7 (A/H7) infection and completed a health questionnaire about type of symptoms, duration of illness, and possible exposures to infected poultry. FINDINGS: 453 people had health complaints--349 reported conjunctivitis, 90 had influenza-like illness, and 67 had other complaints. We detected A/H7 in conjunctival samples from 78 (26.4%) people with conjunctivitis only, in five (9.4%) with influenza-like illness and conjunctivitis, in two (5.4%) with influenza-like illness only, and in four (6%) who reported other symptoms. Most positive samples had been collected within 5 days of symptom onset. A/H7 infection was confirmed in three contacts (of 83 tested), one of whom developed influenza-like illness. Six people had influenza A/H3N2 infection. After 19 people had been diagnosed with the infection, all workers received mandatory influenza virus vaccination and prophylactic treatment with oseltamivir. More than half (56%) of A/H7 infections reported here arose before the vaccination and treatment programme. INTERPRETATION: We noted an unexpectedly high number of transmissions of avian influenza A virus subtype H7N7 to people directly involved in handling infected poultry, and we noted evidence for person-to-person transmission. Our data emphasise the importance of adequate surveillance, outbreak preparedness, and pandemic planning.

            Descriptors:  avian influenza A virus, transmission, humans, outbreak, poultry farms, sub type H7N7.

Kosiakov, P.N., V.S. Pankratov, and Z.I. Rovnova (1979). Antigeny gemaggliutininov virusov grippa, vydelennykh ot cheloveka i ptits. [Hemagglutinin antigens of influenza viruses isolated from man and birds]. Voprosy Virusologii (3): 242-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Immunological analysis has shown hemagglutinins of avian viruses like hemagglutinins of human viruses to have a complex antigenic composition. Three antigenic determinants were discovered in hemagglutinin of A/Chicken/12/71 virus previously designated H3 and in hemagglutinin of A/Tern/18/73 virus previously designated Hav7. The H3 determinant and the second determinant are identical in avian and A/Hong Kong/1/68 human viruses. In addition, hemagglutinins of avian viruses have a determinant specific for each virus which is lacking in human influenza virus hemagglutinin.

            Descriptors:  antigens, viral isolation and purification, birds microbiology, hemagglutinins viral isolation and purification, influenza A virus avian immunology, human immunology, adsorption, chick embryo, complement fixation tests, epitopes, hemagglutination inhibition tests.

Krichevets, S.G., N.L. Varich, I.A. Rudneva, and N.V. Kaverin (1999). Relationship between antigenic characteristics of human and avian influenza virus NP protein and strain variations of amino acid sequences. Voprosy Virusologii 44(4): 158-162.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Human and avian influenza A strains with a known amino acid sequence of NP protein were studied in radioimmunoprecipitation test with a panel of anti-NP monoclonal antibodies. Two of 7 MAbs (315 and IVE8) reacted with variable epitopes. One of the epitopes was present only in human strains, while the other in both human and avian strains, but absent in gull strains and in one human strain, A/Puerto Rico/8/34 (H1N1). The variations recognized by antibodies 315 and IVE8 correlated with amino acid substitutes in positions 16 and 353, respectively.

            Descriptors:  biochemistry and molecular biophysics, infection, amino acid substitution molecular variability.

Kroes, A.C., W.J. Spaan, and E.C. Claas (2004). Van vogelpest tot influenzapandemie; reden tot voorzorgen. [From fowl plague to influenza pandemic; a reason for taking precautions]. Nederlands Tijdschrift Voor Geneeskunde 148(10): 458-63.  ISSN: 0028-2162.

            Abstract:  Throughout Eastern Asia, there is currently an epidemic of fowl plague or highly pathogenic avian influenza, on an unprecedented scale. The prospects for rapid containment are poor. The causative virus, influenza A of the H5N1 subtype, is of limited infectivity for humans. If infection occurs, however, then the consequences are serious and even fatal in a majority of cases. In view of the receptor specificity of avian influenza viruses, this may be related to individually increased susceptibility, which does not lead to further spread. However, it is known that influenza A viruses can readily adapt to replication in the human host by the acquisition of specific gene segments or even by mutations of the avian virus. The extreme scale of human contact with influenza virus of the H5N1 subtype at present engenders fear that there is a high risk of such adaptation and a subsequent pandemic spread. Adequate precautions are necessary, not only in terms of an acceleration of vaccine production but primarily in arranging for sufficient availability of the new antiviral drugs.

            Descriptors:  disease outbreaks, influenza A virus, avian pathogenicity, human pathogenicity, avian influenza transmission, zoonoses, chickens, avian genetics, human genetics.

Ku, A.S.W. and L.T.W. Chan (1999). The first case of H5N1 avian influenza infection in a human with complications of adult respiratory distress syndrome and Reye's syndrome. Journal of Paediatrics and Child Health 35(2): 207-209.  ISSN: 1034-4810.

            Abstract:  Avian influenza virus was not known to cause systemic infection in humans before. We report a 3-year-old boy with good past health who developed pneumonia caused by H5N1 avian influenza A virus (A/Hong Kong/156/97). The virus was isolated from a tracheal aspirate. There were complications of Reye's syndrome, adult respiratory distress syndrome, and multiple organ system failure. He had a history of receiving aspirin. His adult respiratory distress syndrome did not respond to endotracheal surfactant replacement therapy. He died 6 days after admission. Clinicians should be alert to the importance of a new human influenza strain.

            Descriptors:  infection, pediatrics, pulmonary medicine, adult respiratory distress syndrome, respiratory system disease, pneumonia, respiratory system disease, H5N1 avian influenza infection, first case, respiratory system disease, viral disease, Reye's syndrome, digestive system disease, nervous system disease, endotracheal surfactant replacement therapy therapeutic method, case study.

Kul'kova, L.V. and V.Z. Soloukhin (1979). Reproduktsiia virusa istinnoi chumy ptits v organizme komarov Aedes aegypti. [Classical fowl plague virus reproduction in the body of Aedes aegypti mosquitoes]. Voprosy Virusologii (6): 652-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  The results of the studies on fowl plague virus (FPV, Rostok strain) reproduction in Aedes aegypti mosquitoes are presented. The virus-containing allantoic fluid was inoculated intrathoracally in volumes of 0.1 and 0.2 microliter. The virus was isolated in chick embryos and could be detected at 5--14 days after inoculation. After inoculation of 0.1 microliter of virus it could be detected in doses of 0.5, 2.0, 1.75 Ig2 ID50, after inoculation of 0.2 microliter--in doses of 5, 1.5, and 0.5 Ig2 ID50.

            Descriptors:  Aedes microbiology, influenza A virus avian physiology, time factors, virus replication.

Kurtz, J., R.J. Manvell, and J. Banks (1996). Avian influenza virus isolated from a woman with conjunctivitis. Lancet 348(9031): 901-902.

            NAL Call Number:  448.8 L22

            Descriptors:  viroses, women, conjunctivitis, mankind, zoonoses, avian influenza virus, eye diseases, infectious diseases, influenza virus, mankind, organic diseases, orthomyxoviridae, viruses, influenza.

L'vov, D.K., R.I.A. Podcherniaeva, R. Webster, M.V. Ronina, and T.V. Pysina (1979). Poluchenie rekombinantov, antigenno identichynykh tsirkuliruiushchim v prirode shtammam virusa grippa. [Production of recombinants antigenically identical to influenza virus strains circulating in nature]. Voprosy Virusologii (5): 493-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Recombination of a human influenza virus with an avian influenza virus produced a H2Nav2 recombinant with the antigenic properties analogous to those of avian influenza virus (H2Nav2) isolated from wild ducks in the Far East, USSR. Recombination of two avian influenza viruses yielded a recombinant H2N2, an antigenic analogues of influenza A/Singapore/1/57 (H2N2) virus which had started an epidemic of influenza in 1957.

            Descriptors:  antigens, viral genetics, influenza A virus genetics, recombination, genetic, animals, wild, crosses, genetic, ducks microbiology, hemagglutination inhibition tests, influenza A virus human genetics, neuraminidase antagonists and inhibitors.

L'vov, D.K., A.N. Slepushkin, S.S. Iamnikova, and E.I. Burtseva (1998). Gripp ostaetsia nepredskazuemoi infektsiei. [Influenza remains an unpredictable infection]. Voprosy Virusologii 43(3): 141-4.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Influenza virus A (H5N1) was isolated from the tracheal swab of a 3-year-old boy who died from influenza with the Raye syndrome in Hong Kong in May, 1997. Up to the present time, influenza viruses with hemagglutinin H5 were known to circulate only among birds. They caused a variety of diseases: from asymptomatic to epizootic with 100% mortality, particularly among chickens. The main difference between virulent and avirulent strains is as follows: virulent viruses are isolated from all tissues of an infected bird. A (H5) virus hemagglutinin, transformed into a virulent variant, becomes sensitive to cleavage by proteases of mammalian and avian cells. Intensive epidemiological surveillance of influenza in Hong Kong started by the WHO and Department of Public Health of Hong Kong in August-September, 1997, resulted in detection of 17 more cases with Influenza A (H5N1) in November-December 1997. all of the occurred before December 28, 1997 and were detected in hospitals and health centers of Hong Kong. Nine patients were children aged under 5 years. Six patients died as a result of complications (pneumonia) and exacerbations of concomitant chronic diseases. Virological and logical studies showed that the main route of infection transmission was from birds to humans. Human to human transmission is probable. Study of 7 influenza A (H5N1) viruses isolated from patients showed that they contained all 8 RNA gene segments of avian virus. There are no reports about new cases of influenza A (H5N1) in humans in January 1998, and we can hope that the outbreak of Influenza A (H5N1) in Hong Kong caused by avian virus will not develop into a new influenza pandemic, although an unfavorable course of events is probable.

            Descriptors:  influenza virology, influenza A virus avian pathogenicity, chickens virology, Hong Kong epidemiology, influenza epidemiology, influenza physiopathology, avian genetics, RNA, viral, virulence.

Lang, G., A. Gagnon, and J.R. Geraci (1981). Isolation of an influenza A virus from seals. Archives of Virology 68(3-4): 189-95.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Influenza A virus of serotype Hav1 Neq1 (H7N7 by the 1980 revised influenza typing system proposed by WHO experts) was repeatedly isolated from lung and brain tissues taken from harbor seals (Phoca vitulina) found suffering from pneumonia on Cape Cod Peninsula (U.S.A.) in the winter of 1979-1980. The seal isolates, although of a serotype identical to some fowl plaque virus strains, were harmless to chickens and turkeys in transmission experiments. An earlier human infection by a Hav1 Neq1 influenza virus and the serologic relatedness of this avian serotype with the equine 1 serotype are cited in support of the view that influenza viruses with these antigenic characteristics seem to have a facility to pass from birds to mammals.

            Descriptors:  influenza microbiology, influenza A virus avian isolation and purification, Pinnipedia microbiology, pneumonia, viral microbiology, seals microbiology, antigens, viral immunology, brain microbiology, epitopes, avian immunology, lung microbiology.

Langlois, I. (2005). Viral diseases of ferrets. Veterinary Clinics of North America. Exotic Animal Practice 8(1): 139-60.  ISSN: 1094-9194.

            NAL Call Number:  SF997.5.E95E97

            Abstract:  Distemper and rabies vaccination are highly recommended because of the almost invariable fatal outcome of these conditions. Vaccination should constitute an important part of a ferret's preventative medicine program. With the current and anticipated development and licensing of new vaccines, practitioners are invited to gain awareness of the latest vaccine information. Establishment of a practice vaccination protocol with regards to the site of administration of rabies and distemper vaccines is paramount to document any future abnormal tissue reactions. Influenza is the most common zoonotic disease that is seen in ferrets. Although it generally is benign in most ferrets, veterinarians must take this condition seriously. The characteristic continuous antigenic variation of this virus may lead to more virulent strains; the recent emergence of avian influenza virus outbreaks; and the increased susceptibility of elderly, young, and immunosuppressed individuals.

            Descriptors:  ferrets virology, virus diseases veterinary, viruses isolation and purification, virus diseases diagnosis, virus diseases pathology, virus diseases prevention and control, viruses pathogenicity, diagnosis differential, virology.

Lashley, F.R. (2004). Emerging infectious diseases: vulnerabilities, contributing factors and approaches. Expert Review of Anti Infective Therapy 2(2): 299-316.  ISSN: 1478-7210.

            Abstract:  We live in an ever more connected global village linked through international travel, politics, economics, culture and human-human and human-animal interactions. The realization that the concept of globalization includes global exposure to disease-causing agents that were formerly confined to small, remote areas and that infectious disease outbreaks can have political, economic and social roots and effects is becoming more apparent. Novel infectious disease microbes continue to be discovered because they are new or newly recognized, have expanded their geographic range, have been shown to cause a new disease spectrum, have jumped the species barrier from animals to humans, have become resistant to antimicrobial agents, have increased in incidence or have become more virulent. These emerging infectious disease microbes may have the potential for use as agents of bioterrorism. Factors involved in the emergence of infectious diseases are complex and interrelated and involve all classifications of organisms transmitted in a variety of ways. In 2003, outbreaks of interest included severe acute respiratory syndrome, monkeypox and avian influenza. Information from the human genome project applied to microbial organisms and their hosts will provide new opportunities for detection, diagnosis, treatment, prevention, control and prognosis. New technology related not only to genetics but also to satellite and monitoring systems will play a role in weather, climate and the approach to environmental manipulations that influence factors contributing to infectious disease emergence and control. Approaches to combating emerging infectious diseases include many disciplines, such as animal studies, epidemiology, immunology, ecology, environmental studies, microbiology, pharmacology, other sciences, health, medicine, public health, nursing, cultural, political and social studies, all of which must work together. Appropriate financial support of the public health infrastructure including surveillance, prevention, communication, adherence techniques and the like will be needed to support efforts to address emerging infectious disease threats.

            Descriptors:  communicable diseases, emerging economics, prevention and control, emerging transmission, climate, demography, disease susceptibility, disease transmission prevention and control, industry, politics, social conditions, economics, technology, travel, weather.

Laver, G. and E. Garman (2002). Pandemic influenza: its origin and control. Microbes and Infection Institut Pasteur 4(13): 1309-16.  ISSN: 1286-4579.

            NAL Call Number:  QR180.M53

            Abstract:  A "new" influenza virus will appear at some time in the future. This virus will arise by natural processes, which we do not fully understand, or it might be created by some bioterrorist. The world's population will have no immunity to the new virus, which will spread like wild-fire, causing much misery, economic disruption and many deaths. Vaccines will take time to develop and the only means of control, at least in the early stages of the epidemic, are anti-viral drugs, of which the neuraminidase inhibitors currently seem the most effective.

            Descriptors:  disease outbreaks prevention and control, influenza epidemiology, influenza prevention and control, antiviral agents therapeutic use, birds, chickens, China epidemiology, drug resistance, viral, influenza drug therapy, influenza virology, influenza A virus avian classification, avian physiology, models, molecular, neuraminidase physiology, orthomyxoviridae genetics, orthomyxoviridae immunology.

Laver, G. and E. Garman (2001). Virology. The origin and control of pandemic influenza. Science 293(5536): 1776-7.  ISSN: 0036-8075.

            NAL Call Number:  470 Sci2

            Descriptors:  chickens virology, influenza epidemiology, influenza prevention and control, influenza A virus enzymology, influenza A virus pathogenicity, antiviral agents therapeutic use, drug industry methods, drug resistance, microbial, enzyme inhibitors therapeutic use, hn protein chemistry, hn protein genetics, hn protein metabolism, Hong Kong epidemiology, influenza diagnosis, influenza drug therapy, influenza A virus avian enzymology, avian genetics, avian immunology, avian pathogenicity, human enzymology, human genetics, human immunology, human pathogenicity, influenza A virus genetics, influenza A virus immunology, influenza vaccine biosynthesis, influenza vaccine economics, influenza vaccine immunology, models, molecular, mutation genetics, neuraminidase antagonists and inhibitors, neuraminidase chemistry, neuraminidase genetics, neuraminidase metabolism, protein conformation, RNA viral analysis, viral genetics, reassortant viruses enzymology, reassortant viruses genetics, reassortant viruses immunology, reassortant viruses pathogenicity, sialic acids therapeutic use.

Lazzari, S. and K. Stohr (2004). Avian influenza and influenza pandemics. Bulletin of the World Health Organization 82(4): 242.  ISSN: 0042-9686.

            NAL Call Number:  449.9 W892B

            Descriptors:  disease outbreaks prevention and control, influenza epidemiology, influenza A virus, avian pathogenicity, influenza prevention and control, influenza transmission, influenza virology, avian influenza epidemiology, avian influenza transmission, avian influenza virology, sentinel surveillance, world health, zoonoses virology.

Lee, P.J. and L.R. Krilov (2005). When animal viruses attack: SARS and avian influenza. Pediatric Annals 34(1): 42-52.  ISSN: 0090-4481.

            NAL Call Number:  RJ1.P35

            Abstract:  SARS and avian influenza have many common features. They both arose in Asia and originated from animal viruses. They both have the potential to become pandemics because human beings lack antibodies to the animal-derived antigens present on the viral surface and rapid dissemination can occur from the relative ease and availability of high speed and far-reaching transportation methods. Pediatricians, in particular, should remain alert about the possibility of pandemic illnesses in their patients. Annual rates of influenza in children may be 1.5 to 3 times those in the adult population, and infection rates during a community epidemic may exceed 40% in preschool-aged children and 30% in school-aged children. Infected children also play a central role in disseminating influenza, as they are the major point of entry for the virus into the household, from which adults spread disease into the community. Of course, children younger than 24 months also are at high risk for complications from influenza. A 1999 Centers for Disease Control and Prevention projection of an influenza pandemic in the US paints a grim picture: 89,000 to 207,000 deaths, 314,000 to 734,000 hospitalizations, 18 million to 42 million outpatient visits, and 20 million to 47 million additional illnesses, at a cost to society of at least dollars 71.3 billion to dollars 166.5 billion. High-risk patients (15% of the population) would account for approximately 84% of all deaths. Although SARS has been kind to the pediatric population so far, there are no guarantees that future outbreaks would be as sparing. To aid readers in remaining up-to-date with SARS and avian influenza, some useful websites are listed in the Sidebar. Two masters of suspense, Alfred Hitchcock and Stephen King, may have been closer to the truth than they ever would have believed. Both birds and a super flu could bring about the end of civilization as we know it. But all is not lost--to paraphrase Thomas Jefferson, the price of health is eternal vigilance. Although we may not be able to prevent future pandemics, mankind has the ability to recognize new diseases and outbreaks as they occur, to study these infections and find ways to contain and treat them, and to implement the necessary measures to defeat them.

            Descriptors:  avian influenza prevention and control, severe acute respiratory syndrome prevention and control, adult, child, antiviral agents therapeutic use, disease outbreaks prevention and control, disease vectors, avian influenza diagnosis, avian influenza epidemiology, avian influenza transmission, pediatrics methods, population surverillance methods, severe acute respiratory syndrome diagnosis, severe acute respiratory syndrome epidemiology, severe acute respiratory syndrome transmission, world health, SARS.

Leneva, I.A., O. Goloubeva, R.J. Fenton, M. Tisdale, and R.G. Webster (2001). Efficacy of zanamivir against avian influenza A viruses that possess genes encoding H5N1 internal proteins and are pathogenic in mammals. Antimicrobial Agents and Chemotherapy 45(4): 1216-24.  ISSN: 0066-4804.

            NAL Call Number:  RM265.A5132

            Abstract:  In 1997, an avian H5N1 influenza virus, A/Hong Kong/156/97 (A/HK/156/97), caused six deaths in Hong Kong, and in 1999, an avian H9N2 influenza virus infected two children in Hong Kong. These viruses and a third avian virus [A/Teal/HK/W312/97 (H6N1)] have six highly related genes encoding internal proteins. Additionally, A/Chicken/HK/G9/97 (H9N2) virus has PB1 and PB2 genes that are highly related to those of A/HK/156/97 (H5N1), A/Teal/HK/W312/97 (H6N1), and A/Quail/HK/G1/97 (H9N2) viruses. Because of their similarities with the H5N1 virus, these H6N1 and H9N2 viruses may have the potential for interspecies transmission. We demonstrate that these H6N1 and H9N2 viruses are pathogenic in mice but that their pathogenicities are less than that of A/HK/156/97 (H5N1). Unadapted virus replicated in lungs, but only A/HK/156/97 (H5N1) was found in the brain. After three passages (P3) in mouse lungs, the pathogenicity of the viruses increased, with both A/Teal/HK/W312/97 (H6N1) (P3) and A/Quail/HK/G1/97 (H9N2) (P3) viruses being found in the brain. The neuraminidase inhibitor Zanamivir inhibited viral replication in Madin-Darby canine kidney cells in virus yield assays (50% effective concentration, 8.5 to 14.0 microM) and inhibited viral neuraminidase activity (50% inhibitory concentration, 5 to 10 nM). Twice daily intranasal administration of Zanamivir (50 and 100 mg/kg of body weight) completely protected infected mice from death. At a dose of 10 mg/kg, Zanamivir completely protected mice from infection with H9N2 viruses and increased the mean survival day and the number of survivors infected with H6N1 and H5N1 viruses. Zanamivir, at all doses tested, significantly reduced the virus titers in the lungs and completely blocked the spread of virus to the brain. Thus, Zanamivir is efficacious in treating avian influenza viruses that can be transmitted to mammals.

            Descriptors:  antiviral agents therapeutic use, enzyme inhibitors therapeutic use, influenza drug therapy, influenza A virus avian drug effects, neuraminidase antagonists and inhibitors, sialic acids therapeutic use, administration, intranasal, antiviral agents administration and dosage, antiviral agents pharmacology, brain virology, cell line, dogs, enzyme inhibitors administration and dosage, enzyme inhibitors pharmacology, genes viral, influenza virology, avian genetics, avian pathogenicity, kinetics, lung virology, mice, mice inbred BALB c, microbial sensitivity tests, sialic acids administration and dosage, sialic acids pharmacology, species specificity, virus replication drug effects.

Leneva, I.A., N. Roberts, E.A. Govorkova, O.G. Goloubeva, and R.G. Webster (2000). The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Research 48(2): 101-15.  ISSN: 0166-3542.

            NAL Call Number:  QR355.A5

            Abstract:  In 1997, an H5N1 avian influenza A/Hong Kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. In 1999, another avian A/Hong/1074/99 (H9N2) virus caused influenza in two children. In such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. Here we demonstrate the efficacy of the neuraminidase inhibitor GS4104 (oseltamivir phosphate) against these H5N1 and H9N2 viruses. GS4071 (the active metabolite of oseltamivir) inhibited viral replication in MDCK cells (EC(50) values, 7.5-12 microM) and neuraminidase activity (IC(50) values, 7.0-15 nM). When orally administered at doses of 1 and 10 mg/kg per day, GS4104 prevented death of mice infected with A/Hong Kong/156/97 (H5N1), mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2), or human A/Hong Kong/1074/99 (H9N2) viruses and reduced virus titers in the lungs and prevented the spread of virus to the brain of mice infected with A/Hong Kong/156/97 (H5N1) and mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2) viruses. When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control. Oral administration of GS4104 (0.1 mg/kg per day) in combination with rimantadine (1 mg/kg per day) reduced the number of deaths of mice infected with 100 MLD(50) of H9N2 virus and prevented the deaths of mice infected with 5 MLD(50) of virus. Thus, GS4104 is efficacious in treating infections caused by H5N1 and H9N2 influenza viruses in mice.

            Descriptors:  acetamides pharmacology, antiviral agents pharmacology, influenza drug therapy, influenza A virus avian drug effects, human drug effects, neuraminidase antagonists and inhibitors, acetamides therapeutic use, antiviral agents therapeutic use, brain virology, cell line, dogs, enzyme inhibitors pharmacology, enzyme inhibitors therapeutic use, influenza virology, avian enzymology, avian pathogenicity, human enzymology, human pathogenicity, kidney, lung virology, mice, mice inbred BALB c, neuraminidase metabolism, rimantadine therapeutic use, virus replication drug effects.

Lesník, F., N. Ucekaj, O. Ondrasovicová, and V. Bajová (2003). A highly virulent avian influenza virus in Europe. Slovenský Veterinársky Casopis 28(3): 31-32.  ISSN: 1335-0099.

            Descriptors:  disease control, mutations, virulence, avian influenza virus, ducks, Europe.

Letonturier, P. (2004). Quand les virus attaquent. [When viruses attack]. Presse Medicale Paris, France 1983 33(6): 428.  ISSN: 0755-4982.

            Descriptors:  disease outbreaks, influenza A virus, avian influenza, avian influenza epidemiology, avian influenza transmission, zoonoses, poultry, risk factors.

Li, S., M.L. Perdue, and E. Patzer (2002). Seed viruses containing novel avian HA and NA antigens for prevention against potential influenza pandemic. Developments in Biologicals 110: 135-41.  ISSN: 1424-6074.

            NAL Call Number:  QR180.3.D4

            Abstract:  An influenza pandemic could arise unexpectedly with rapid spread across the world. The efficiency of production of a vaccine and the ability to administer it widely will be among the most important factors in the ability to protect public health. The current process for producing inactivated or live attenuated influenza vaccines requires six to nine months. That reduces considerably the likelihood that the vaccine will be available during the first wave of the pandemic. Therefore, a key element of preparedness is to optimize the production process and to reduce the vaccine development time. During the 1997 H5N1 outbreak in Hong Kong, seed viruses were prepared for production of inactivated and live-attenuated vaccines. We used the cold-adapted A/Ann Arbor/6/60 as the donor virus to generate live attenuated vaccines containing genetically modified HA and NA genes from H5N1 influenza viruses. These reassortants were shown to be safe and protective in animal models. This study indicates that production of live attenuated avian influenza vaccines is feasible and that development of a library of reassortants containing different subtype HA and NA genes may reduce the vaccine preparation time for future influenza pandemics.

            Descriptors:  antigens, viral immunology, influenza prevention and control, influenza A virus avian immunology, influenza epidemiology, influenza vaccine administration and dosage.

Li, S.Q., M. Orlich, and R. Rott (1990). Generation of seal influenza virus variants pathogenic for chickens, because of hemagglutinin cleavage site changes. Journal of Virology 64(7): 3297-303.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza virus A/seal/Mass/1/80 (H7N7) was adapted to grow in MDCK cells and chicken embryo cells (CEC) in the absence of exogenous protease. The biological properties of the virus variants obtained coincided with intracellular activation of the hemagglutinin (HA) by posttranslational proteolytic cleavage and depended on the cell type used for adaptation. MDCK cell-adapted variants contained point mutations in regions of the HA more distant from the cleavage site. It is proposed that these mutations are probably responsible, through an unknown mechanism, for enhanced cleavability of HA in MDCK cells. Such virus variants were apathogenic in chickens. CEC-adapted variants, on the other hand, contained an insertion of basic amino acids at the HA cleavage site, in addition to scattered point mutations. The insertions converted the cleavage sites in the variant virus HAs so that they came to resemble the cleavage site found in highly pathogenic avian influenza viruses. CEC variants with such cleavage site modifications were highly pathogenic for chickens. The lethal outcome of the infection in chickens demonstrated for the first time that an influenza virus derived from a mammalian species can be modified during adaptation to a new cell type to such an extent that the resulting virus variant becomes pathogenic for an avian species.

            Descriptors:  chickens microbiology, hemagglutinins viral metabolism, influenza A virus pathogenicity, pinnipedia microbiology, seals microbiology, amino acid sequence, base sequence, cell line, chick embryo, dogs, electrophoresis, gel, two dimensional, hemagglutinins viral genetics, influenza A virus genetics, molecular sequence data, mutation, peptide hydrolases metabolism, species specificity, virus replication.

Liem, N.T. (2005). Lack of H5N1 avian influenza transmission to hospital employees, Hanoi, 2004. Emerging Infectious Diseases 11(2): 210-5.  ISSN: 1080-6040.

            NAL Call Number:  RA648.5.E46

            Abstract:  To establish whether human-to-human transmission of influenza A H5N1 occurred in the healthcare setting in Vietnam, we conducted a cross-sectional seroprevalence survey among hospital employees exposed to 4 confirmed and 1 probable H5N1 case-patients or their clinical specimens. Eighty-three (95.4%) of 87 eligible employees completed a questionnaire and provided a serum sample, which was tested for antibodies to influenza A H5N1. Ninety-five percent reported exposure to >1 H5N1 case-patients; 59 (72.0%) reported symptoms, and 2 (2.4%) fulfilled the definition for a possible H5N1 secondary case-patient. No study participants had detectable antibodies to influenza A H5N1. The data suggest that the H5N1 viruses responsible for human cases in Vietnam in January 2004 are not readily transmitted from person to person. However, influenza viruses are genetically variable, and transmissibility is difficult to predict. Therefore, persons providing care for H5N1 patients should continue to take measures to protect themselves.

            Descriptors:  patient to professional disease transmission, health personnel, influenza transmission, avian influenza A virus growth and development, Western blotting, child, preschool child, adolescent, adult, viral blood antibodies, cross sectional studies, influenza immunology, influenza virology, avian influenza A virus immunology, middle-aged, neutralization tests, questionnaires, seroepidemiologic studies, Vietnam epidemiology.

Lin, Y.P., M. Shaw, V. Gregory, K. Cameron, W. Lim, A. Klimov, K. Subbarao, Y. Guan, S. Krauss, K. Shortridge, R. Webster, N. Cox, and A. Hay (2000). Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates. Proceedings of the National Academy of Sciences of the United States of America 97(17): 9654-8.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. Slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of H5N1 infection have occurred. In March 1999, however, a new pandemic threat appeared when influenza A H9N2 viruses infected two children in Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a quail in Hong Kong in late 1997. Although differing in their surface hemagglutinin and neuraminidase components, a notable feature of these H9N2 viruses is that the six genes encoding the internal components of the virus are similar to those of the 1997 H5N1 human and avian isolates. This common feature emphasizes the apparent propensity of avian viruses with this genetic complement to infect humans and highlights the potential for the emergence of a novel human pathogen.

            Descriptors:  bird diseases transmission, influenza transmission, influenza A virus avian genetics, influenza A virus genetics, influenza A virus immunology, quail virology, antigens, viral chemistry, antigens, viral genetics, antigens, viral immunology, binding sites,  bird diseases epidemiology, child, preschool, conserved sequence genetics, genes viral genetics, hemagglutinins viral chemistry, hemagglutinins viral genetics, hemagglutinins viral immunology, Hong Kong epidemiology, infant, influenza epidemiology, avian chemistry, avian classification, avian immunology, influenza A virus chemistry,  influenza A virus classification, molecular sequence data, neuraminidase chemistry, neuraminidase genetics, neuraminidase immunology, phylogeny, species specificity, variation genetics genetics.

Lin, Y.P., L.L. Shu, S. Wright, W.J. Bean, G.B. Sharp, K.F. Shortridge, and R.G. Webster (1994). Analysis of the influenza virus gene pool of avian species from southern China. Virology 198(2): 557-566.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Although Southern China has been considered the epicenter of human influenza pandemics, little is known about the genetic composition of influenza viruses in lower mammals or birds in that region. To provide information on the molecular epidemiology of these viruses, we used dot blot hybridization and phylogenetic methods to study the internal genes (PB1, PB2, PA, NP, M, and NS) of 106 avian influenza A viruses isolated from a total of 11,798 domestic ducks, chickens, and geese raised in Southern China including Hong Kong. All 636 genes examined were characteristic of avian influenza viruses; no human or swine influenza genes were detected. Thus, influenza virus reassortants do not appear to be maintained in the domesticated birds of Southeast Asia, eliminating opportunities for further gene reassortment. Phylogenetic analysis showed that the internal genes of these viruses belong to the Eurasian avian lineage, supporting geographical separation of the major avian lineages. The PB1 genes were most similar to A/Singapore/57 (H2N2) and Hong Kong (H3N2) viral genes, supporting an avian origin for the recent human H2N2 and H3N2 pandemic strains. The majority of internal genes from avian influenza viruses in Southern China belong to the Eurasian lineage and are similar to viruses that have recently been transmitted to humans, swine, and horses. This study provides evidence that the transmission of avian influenza viruses and their genes to other species is unidirectional and that the transmission of mammalian influenza virus strains to domestic poultry is probably not a factor in the generation of new pandemic strains.

            Descriptors:  poultry, China, Hong Kong, avian influenza virus, genes, phylogeny, nucleotide sequence, mankind, epidemiology, Asia, cell structure, chromosomes, domestic animals, domesticated birds, East Asia, evolution, genomes, influenza virus, livestock, nucleus,  useful animals, viruses, pandemics, sequence homology, gene flow, comparisons, man.

Lina, B. (2004). A gripe das aves desperta o terror de uma pandemia. [Avian influenza causes fear about a pandemic.]. Servir Lisbon, Portugal 52(2): 93-5.  ISSN: 0871-2379.

            Descriptors:  influenza, avian epidemiology, influenza, avian transmission.

Lindstrom, S.E., N.J. Cox, and A. Klimov (2004). Evolutionary analysis of human H2N2 and early H3N2 influenza viruses: evidence for genetic divergence and multiple reassortment among H2N2 and/or H3N2 viruses. International Congress Series 1263: 184-190.

            Abstract:  Pandemic influenza H2N2 viruses emerged in humans in 1957 and caused widespread morbidity and mortality in humans until 1968 when they were displaced by emerging H3N2 viruses. Although it is known that both the appearance and disappearance of H2N2 viruses involved reassortment between human and avian influenza viruses, genetic characterization of these viruses is limited. In this study, detailed genetic analysis of all eight gene segments of human H2N2 viruses isolated from 1957 until 1968 from geographically diverse regions was undertaken to establish a better understanding of the evolutionary nature of this virus. In addition, a number of human H3N2 viruses isolated from 1968 until 1972 were examined to investigate genetic events associated with the emergence of pandemic H3N2 viruses in humans. Phylogenic analysis of all gene segments of human H2N2 viruses consistently demonstrated divergent evolution. Genes of late H2N2 isolates were located in either of two distinct clades (I and II). Analysis of H3N2 viruses of 1968 revealed that all gene segments that were retained from H2N2 viruses were most similar to H2N2 virus genes of clade I. However, genes of both lineages were found to cocirculate among H3N2 isolates of 1969-1971. Furthermore, each gene segment demonstrated unique phylogenic topologies, indicating multiple reassortment events between late H2N2 and/or H3N2 viruses. The H3N2 viruses of 1972 analyzed here appeared to possess the genome constellation that represents the ancestral virus of contemporary H3N2 viruses. This constellation was first observed among isolates of 1970 and was distinct from that found among the earliest human H3N2 viruses from 1968. This evidence demonstrates that establishment of H3N2 viruses in humans was associated with multiple-reassortment events that contributed to genetic diversity among viruses.

            Descriptors:  influenza, H2N2, H3N2, evolution, reassortment, hemagglutinin, neuraminidase, nucleoprotein, influenza virus genetics.

Lipatov, A.S., A.K. Gitel'man, E.A. Govorkova, and Y.U.A. Smirnov (1995). Izmeneniya biologicheskikh i fiziko-khimicheskikh svojstv gemagglyutinina H2 ptich' ego virusa grippa A v protsesse adaptatsii k novomu khozyainu. [Alteration of the biological and physicochemical characteristics of hemagglutinin H2 of avian influenza A virus in the course of adaptation to a new host]. Voprosy Virusologii 40(5): 208-211.

            NAL Call Number:  448.8 P942

            Abstract:  Avian influenza A virus with H2 hemagglutinin has been adapted to mice for the first time. Alterations in the hemagglutinin of adapted variants of the virus as a result of adaptation to a new host are described. Hemagglutinin of a hightly virulent adapted variant differed from the parental avirulent strain by antigenic structure, electrophoretic mobility, and receptor activity during interactions with murine red cells.

            Descriptors:  laboratory animals, avian influenza virus, pathotypes, host pathogen relations, adaptation, agglutinins, immunological factors, biological properties, chemicophysical properties, experimental infection, in vivo experimentation, mice, biotypes, disease transmission, experimentation, infection, influenza virus, mammals, orthomyxoviridae, pathogenesis, pathology, proteins, Rodentia, useful animals, viruses.

Lipatov, A.S., A.K. Gitelman, E.A. Govorkova, and Y.U.A. Smirnov (1995 ). Changes of morphological, biological and antigenic properties of avian influenza A virus haemagglutinin H2 in the course of adaptation to new host. Acta Virologica 39(5-6): 279-81.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  The alterations of avian influenza A virus haemagglutinin (HA) H2 as a result of adaptation to mice were first investigated in this study. HA of mouse-adapted (MA) variant was somewhat different from that of the original strain in electrophoretical mobility, antigenic structure and in haemagglutination activity with mouse red blood cells.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, adaptation, physiological, cell line, chick embryo, dogs, electrophoresis, polyacrylamide gel, erythrocytes immunology, fowl plague immunology, fowl plague virology, hemagglutination tests, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral chemistry, mice.

Lipatov, A.S., A.K. Gitelman, and Y.U.A. Smirnov (1996). Differences between original strains and their mouse-adapted variants of human (H1) and avian (H2) influenza A viruses in the reaction with cross-neutralizing monoclonal antibody recognizing conformational epitope. Acta Virologica 40(4): 227-30.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Human (H1) and avian (H2) influenza A viruses and their mouse-adapted (MA) variants were studied in radioimmunoprecipitation assay (RIPA) and infectivity neutralization test using a monoclonal antibody (MoAb) directed against a conserved antigenic epitope in the stem region of the haemagglutinin (HA) and reacting both with H1 and H2 subtypes of HA. Whereas the MA variant of avian influenza A virus differed from the original strain in RIPA and neutralization tests, no differences were observed between the original human strain and its MA variant, as well as between the original H1 and H2 strains.

            Descriptors:  antibodies, viral immunology, antigens, viral immunology, epitopes, b lymphocyte immunology, hemagglutinin glycoproteins, influenza virus immunology, influenza A virus avian immunology, human immunology, adaptation, physiological, antibodies, monoclonal immunology, cell line, chick embryo, cross reactions, dogs, glycosylation, mice, neutralization tests, protein conformation, variation genetics.

Lipkind, M. and Y. Weisman (1989). Ecological studies and diagnosis of animal influenza and animal paramyxoviruses in Israel. II. Animal influenza: a review on decade studies. Israel Journal of Veterinary Medicine 45(4): 263-287.  ISSN: 0334-9152.

            NAL Call Number:  41.8 R25

            Descriptors:  DNA hybridization, influenza, paramyxoviruses, disease transmission, reviews, turkeys,  wild birds, ducks, pigs, horses, review, Israel, ecological study.

Lipkind, M., Y. Weisman, E. Shihmanter, D. Shoham, C. Yuval, and A. Aronovici (1980). Evidence for the interspecific transfer of an avian influenza virus. Israel Journal of Medical Sciences 16(6): 475.  ISSN: 0021-2180.

            NAL Call Number:  R97.I87

            Descriptors:  avian influenza virus, transfer, turkeys,  birds, ducks, Israel.

Lisovskaya, K.V., L.M. Garmashova, and T.E. Medvedeva (1981). Analysis of ts mutations of cold-adapted influenza A/Leningrad/134/57 virus variants. Acta Virologica 25(6): 415-7.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  By recombination of ts mutants of fowl plague virus belonging to different complementation groups with two cold-adapted variants of human influenza virus, the number and gene localization of ts mutations occurring in these variants was determined. In the course of passaging of human influenza virus at lowered temperature, the number of genes with ts mutations increased.

            Descriptors:  genes viral, influenza A virus avian genetics, human genetics, cold, genetic complementation test, mutation, recombination, genetic.

Liu, J.H., K. Okazaki, G.R. Bai, W.M. Shi, A. Mweene, and H. Kida (2004). Interregional transmission of the internal protein genes of H2 influenza virus in migratory ducks from North America to Eurasia. Virus Genes  29(1): 81-6.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  H2 influenza virus caused a pandemic in 1957 and has the possibility to cause outbreaks in the future. To assess the evolutionary characteristics of H2 influenza viruses isolated from migratory ducks that congregate in Hokkaido, Japan, on their flyway of migration from Siberia in 2001, we investigated the phylogenetic relationships among these viruses and avian and human viruses described previously. Phylogenetic analysis showed that the PB2 gene of Dk/Hokkaido/107/01 (H2N3) and the PA gene of Dk/Hokkaido/95/01 (H2N2) belonged to the American lineage of avian virus and that the other genes of the isolates belonged to the Eurasian lineage. These results indicate that the internal protein genes might be transmitted from American to Eurasian avian host. Thus, it is further confirmed that interregional transmission of influenza viruses occurred between the North American and Eurasian birds. The fact that reassortants could be generated in the migratory ducks between North American and Eurasian avian virus lineage further stresses the importance of global surveillance among the migratory ducks.

            Descriptors:  ducks virology, emigration and immigration, influenza A virus, avian genetics, influenza, avian virology, viral proteins genetics, Asia, Europe, avian influenza A virus classification, molecular sequence data, North America, phylogeny, sequence analysis, DNA.

Liu, M., Y. Guan, M. Peiris, S. He, R.J. Webby, D. Perez, and R.G. Webster (2003). The quest of influenza A viruses for new hosts. Avian Diseases 47(Special Issue): 849-856.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  There is increasing evidence that stable lineages of influenza viruses are being established in chickens. H9N2 viruses are established in chickens in Eurasia, and there are increasing reports of H3N2, H6N1, and H6N2 influenza viruses in chickens both in Asia and North America. Surveillance in a live poultry market in Nanchang, South Central China, reveals that influenza viruses were isolated form 1% of fecal samples taken from healthy poultry over the course of 16 months. The highest isolation rates were from chickens (1.3%) and ducks (1.2%), followed by quail (0.8%), then pigeon (0.5%). H3N6, H9N2, H2N9, and H4N6 viruses were isolated from multiple samples, while single isolates of HlN1, H3N2, and H3N3 viruses were made. Representatives of each virus subtype were experimentally inoculated into both quail and chickens. All the viruses replicated in the trachea of quail, but efficient replication in chickens was confined to 25% of the tested isolates. In quail, these viruses were shed primarily by the aerosol route, raising the possibility that quail may be the "route modulator" that changes the route of transmission of influenza viruses from fecal-oral to aerosol transmission. Thus, quail may play an important role in the natural history of influenza viruses. The pros and cons of the use of inactivated and recombinant fowl pox-influenza vaccines to control the spread of avian influenza are also evaluated.

            Descriptors:  epidemiology, infection, live poultry market, transmission route, aerosol, fecal, oral, viral, natural history.

Lu, X., D. Cho, H. Hall,  T. Rowe, H. Sung, W. Kim, C. Kang, I. Mo, N. Cox, A. Klimov, and J. Katz (2003). Pathogenicity and antigenicity of a new influenza A (H5N1) virus isolated from duck meat. Journal of Medical Virology 69(4): 553-559.  ISSN: 0146-6615.

            Abstract:  Avian influenza A viruses are the ancestral origin of all human influenza viruses. The outbreak of highly pathogenic (HP) avian H5N1 in Hong Kong in 1997 highlighted the potential of these viruses to infect and cause severe disease in humans. Since 1999, HP H5N1 viruses were isolated several times from domestic poultry in Asia. In 2001, a HP H5N1 virus, A/Duck/Anyang/AVL-1/2001 (Dk/Anyang), was isolated from imported frozen duck meat in Korea. Because of this novel source of HP H5N1 virus isolation, concerns were raised about the potential for human exposure and infection; we therefore compared the Dk/Anyang virus with HP H5N1 viruses isolated from humans in 1997 in terms of antigenicity and pathogenicity for mammals. At high doses, Dk/Anyang virus caused up to 50% mortality in BALB/c mice, was isolated from the brains and lymphoid organs of mice, and caused lymphopenia. Overall Dk/Anyang virus was substantially less pathogenic for mice than the H5N1 virus isolated from a fatal human case in 1997. Likewise, Dk/Anyang virus was apathogenic for ferrets. Dk/Anyang virus was antigenically distinguishable by hemagglutination-inhibition (HI) assay from human H5N1 viruses isolated in 1997 and avian H5N1 viruses isolated in 2001 in Hong Kong. Nevertheless, prior infection with Dk/Anyang virus protected mice from death after secondary infection with HP human H5N1 viruses. These results indicate that compared with HP human H5N1 viruses, Dk/Anyang virus is substantially less pathogenic for mammalian species. Nevertheless, the novel source of isolation of this avian H5N1 virus must be considered when evaluating the potential risk to public health.

            Descriptors:  infection, avian influenza, viral disease, duck meat, meat product.

Lu, X., T.M. Tumpey, T. Morken, S.R. Zaki, N.J. Cox, and J.M. Katz (1999). A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. Journal of Virology 73(7): 5903-11.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  During 1997 in Hong Kong, 18 human cases of respiratory illness, including 6 fatalities, were caused by highly pathogenic avian influenza A (H5N1) viruses. Since H5 viruses had previously been isolated only from avian species, the outbreak raised questions about the ability of these viruses to cause severe disease and death in humans. To better understand the pathogenesis and immunity to these viruses, we have used the BALB/c mouse model. Four H5N1 viruses replicated equally well in the lungs of mice without prior adaptation but differed in lethality for mice. H5N1 viruses that were highly lethal for mice were detected in multiple organs, including the brain. This is the first demonstration of an influenza A virus that replicates systemically in a mammalian species and is neurotropic without prior adaptation. The mouse model was also used to evaluate a strategy of vaccination against the highly pathogenic avian H5N1 viruses, using an inactivated vaccine prepared from nonpathogenic A/Duck/Singapore-Q/F119-3/97 (H5N3) virus that was antigenically related to the human H5N1 viruses. Mice administered vaccine intramuscularly, with or without alum, were completely protected from lethal challenge with H5N1 virus. Protection from infection was also observed in 70% of animals administered vaccine alone and 100% of mice administered vaccine with alum. The protective effect of vaccination correlated with the level of virus-specific serum antibody. These results suggests a strategy of vaccine preparedness for rapid intervention in future influenza pandemics that uses antigenically related nonpathogenic viruses as vaccine candidates.

            Descriptors:  influenza prevention and control, influenza virology, influenza A virus avian immunology, avian pathogenicity, uman immunology, human pathogenicity, cell line, disease models, animal, disease outbreaks, dogs, influenza epidemiology, influenza immunology, avian growth and development, avian isolation and purification, human growth and development, human isolation and purification, influenza vaccine immunology, mice, inbred BALB c, vaccines, inactivated immunology.

Lu, X.H., D. Cho, H. Hall,  T. Rowe, I.P. Mo, H.W. Sung, W.J. Kim, C. Kang, N. Cox, A. Klimov, and J.M. Katz (2003). Pathogenesis of and immunity to a new influenza A (H5N1) virus isolated from duck meat. Avian Diseases 47(Special Issue): 1135-1140.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The outbreak of avian influenza H5N1 in Hong Kong in 1997 raised concerns about the potential for the H5 subtype to cause a human pandemic. In 2001 a new H5N1 virus, A/Duck Meat/Anyang/AVL-1/2001 (A/Dkmt), was isolated from imported duck meat in Korea. The pathogenesis of this virus was investigated in mice. A/Dkmt virus had low infectivity but was lethal for mice at high doses, and at lethal doses, the virus replicated in the brains of infected mice. A/Dkmt virus cross-reacted poorly with ferret antisera raised against human H5N1 viruses, but prior infection with A/Dkmt virus protected mice from death after secondary infection with human H5N1 virus.

            Descriptors:  infection, avian influenza, infectious disease, respiratory system disease, viral disease, disease pathogenesis duck meat, contamination, poultry product, influenza pandemic, viral immunity.

Ludwig, S., A. Haustein, E.F. Kaleta, and C. Scholtissek (1994). Recent influenza A (H1N1) infections of pigs and turkeys in northern Europe. Virology 202(1): 281-286.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The most recent introduction of an avian influenza A virus without reassortment into mammals occurred in 1979 when H1N1 strains could be isolated from diseased pigs in northern Europe. This newly introduced avian virus formed a stable lineage in pigs and, in the meantime, spread all over Europe In 1991 highly pathogenic H1N1 strains closely related to a contemporary swine virus were isolated from turkeys of a breeding farm near Bremen, Germany. Outbreaks in several farms in Germany, France, and the Netherlands indicate that the "avian-like" swine viruses can easily be reintroduced into an avian population causing severe economical losses.

            Descriptors:  swine, Germany, Netherlands, France, turkeys,  swine influenza virus, avian influenza virus, animal viruses, proteins, genes, nucleotide sequence, artiodactyla, birds, cell structure, chromosomes, domestic animals, Europe, Galliformes, genomes, influenza virus, livestock, mammals, Mediterranean countries, nucleus, suidae, useful animals, viruses, western Europe, spread, amino acid sequences, comparisons.

Ludwig, S., L. Stitz, O. Planz, H. Van, W.M. Fitch, and C. Scholtissek (1995). European swine virus as a possible source for the next influenza pandemic? Virology 212(2): 555-561.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  According to phylogenetic data, about 100 years ago an avian influenza virus passed me species barrier (possibly first) to pigs and (possibly from there) to humane. In 1979 an avian influenza A virus (as a whole, without reassortment) again entered the pig population in northern Europe, forming a stable lineage. Here it is shown that the early North European swine viruses exhibit higher than normal evolutionary rates and are highly variable with respect to plaque morphology and neutralizability by monoclonal antibodies. Our results are consistent with the idea that, in order to pass the species barrier, an influenza A virus needs a mutator mutation to provide an additional number of variants, from which the new host might select the best fitting ones. A mutator mutation could be of advantage under such stress conditions and might enable a virus to pass the species barrier as a whole even twice, as it seems to have happened about 100 years ago. This stressful situation should be over for the recent swine lineage, since the viruses seem to be adapted already to the new host in that the most recent isolates--at least in northern Germany--are genetically stable and seem to have lost the putative mutator mutation again.

            Descriptors:  Europe, swine influenza virus, avian influenza virus, influenza virus, mankind, phylogeny, agglutinins, monoclonal antibodies, viruses, antigen antibody reactions, mutation, antibodies, evolution, genetics, immune response, immunity, immunological factors, influenza virus, orthomyxoviridae, proteins, viruses, human influenza virus, mutator mutations, species barriers, northern Europe, viral hemagglutinins, viral morphology, virus neutralization, barriers.

Makarova, K.S., Y.I. Wolf, E.P. Tereza, and V.A. Ratner (1998). Different patterns of molecular evolution of influenza A viruses in avian and human populations. Genetika 34(7): 890-896.  ISSN: 0016-6758.

            NAL Call Number:  QH431.A1G4

            Abstract:  Patterns of molecular evolution of the influenza virus proteins and genes are discussed. The subsets of all viral genes corresponding to statistically significant clusters on dendrogram were shown to fall into two distinct groups. The first group was characterized by the presence of an exact linear relationship between the year of the strain isolation and the evolutionary distance. The subsets of human influenza virus genes belong to this group. A method for eliminating the "frozen" strains from the subsets and for calculating the evolutionary rates without construction of phylogenetic trees has been elaborated. The substitution rates calculated according to this technique agreed with the data obtained previously. A linear relationship was not observed in the second group. This group was predominantly composed of avian influenza virus genes. The lack of linear correlation pointed to the cocirculation of a large amount of different influenza virus genomic segments in the avian population. An approach for an examination of the role of intragenic recombination in the development of the antigenic subtypes of hemagglutinin is suggested. Our results suggest that recombination did not play a considerable role in this process, and that all modern subtypes of this protein were probably formed before the introduction of the influenza viruses into the human population. These findings are consistent with the hypothesis that influenza viruses penetrated into human population from their pools in avian populations.

            Descriptors:  evolution and adaptation, genetics, influenza virus, human, avian.

Makarova, K.S., Y.U.I. Wulf, E.P. Tereza, and V.A. Ratner (1998). Razlichie rezhimov molekuliarnoi evoliutsii virusov grippa A v populiatsiiakh ptits i cheloveka. [Different patterns of molecular evolution of influenza A viruses in avian and human population]. Genetika  34(7): 890-6.  ISSN: 0016-6758.

            NAL Call Number:  QH431.A1G4

            Abstract:  Patterns of molecular evolution of the influenza virus proteins and genes are discussed. The subsets of all viral genes corresponding to statistically significant clusters on dendrogram were shown to fall into two distinct groups. The first group was characterized by the presence of an exact linear relationship between the year of the strain isolation and the evolutionary distance. The subsets of human influenza virus genes belong to this group. A method for eliminating the "frozen" strains from the subsets and for calculating the evolutionary rates without construction of phylogenetic trees has been elaborated. The substitution rates calculated according to this technique agreed with the data obtained previously. A linear relationship was not observed in the second group. This group was predominantly composed of avian influenza virus genes. The lack of linear correlation pointed to the cocirculation of a large amount of different influenza virus genomic segments in the avian population. An approach for an examination of the role of intragenic recombination in the development of the antigenic subtypes of hemagglutinin is suggested. Our results suggest that recombination did not play a considerable role in this process, and that all modern subtypes of this protein were probably formed before the introduction of the influenza viruses into the human population. These findings are consistent with the hypothesis that influenza viruses penetrated into human population from their pools in avian populations.

            Descriptors:  birds genetics, evolution, molecular, genes viral, influenza A virus avian genetics, human genetics, viral proteins genetics.

Makarova, N.V., H. Ozaki, H. Kida, R.G. Webster, and D.R. Perez (2003). Replication and transmission of influenza viruses in Japanese quail. Virology 310(1): 8-15.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Quail have emerged as a potential intermediate host in the spread of avian influenza A viruses in poultry in Hong Kong. To better understand this possible role, we tested the replication and transmission in quail of influenza A viruses of all 15 HA subtypes. Quail supported the replication of at least 14 subtypes. Influenza A viruses replicated predominantly in the respiratory tract. Transmission experiments suggested that perpetuation of avian influenza viruses in quail requires adaptation. Swine influenza viruses were isolated from the respiratory tract of quail at low levels. There was no evidence of human influenza A or B virus replication. Interestingly, a human-avian recombinant containing the surface glycoprotein genes of a quail virus and the internal genes of a human virus replicated and transmitted readily in quail; therefore, quail could function as amplifiers of influenza virus reassortants that have the potential to infect humans and/or other mammalian species.

            Descriptors:  infection, molecular genetics, respiratory system, adaptation.

Marois, P., A. Boudreault, E. DiFranco, and V. Pavilanis (1971). Response of ferrets and monkeys to intranasal infection with human, equine and avian influenza viruses. Canadian Journal of Comparative Medicine Revue Canadienne De Medecine Comparee 35(1): 71-6.  ISSN: 0008-4050.

            NAL Call Number:  41.8 C162

            Descriptors:  Carnivora, influenza veterinary, monkey diseases microbiology, nose microbiology, orthomyxoviridae pathogenicity, respiratory tract infections microbiology, antigen antibody reactions, birds, cross reactions, haplorhini, hemagglutination inhibition tests, horses, immune sera, influenza immunology, orthomyxoviridae isolation and purification, respiratory tract infections immunology, turkeys, virus replication.

Mase, M., T. Imada, Y. Sanada, M. Etoh, N. Sanada, K. Tsukamoto, Y. Kawaoka, and S. Yamaguchi (2001). Imported parakeets harbor H9N2 influenza A viruses that are genetically closely related to those transmitted to humans in Hong Kong. Journal of Virology 75(7): 3490-4.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In 1997 and 1998, H9N2 influenza A viruses were isolated from the respiratory organs of Indian ring-necked parakeets (Psittacula Krameri manillensis) that had been imported from Pakistan to Japan. The two isolates were closely related to each other (>99% as determined by nucleotide analysis of eight RNA segments), indicating that H9N2 viruses of the same lineage were maintained in these birds for at least 1 year. The hemagglutinins and neuraminidases of both isolates showed >97% nucleotide identity with those of H9N2 viruses isolated from humans in Hong Kong in 1999, while the six genes encoding internal proteins were >99% identical to the corresponding genes of H5N1 viruses recovered during the 1997 outbreak in Hong Kong. These results suggest that the H9N2 parakeet viruses originating in Pakistan share an immediate ancestor with the H9N2 human viruses. Thus, influenza A viruses with the potential to be transmitted directly to humans may be circulating in captive birds worldwide.

            Descriptors:  influenza transmission, influenza A virus avian classification, nucleoproteins, parakeets virology, amino acid sequence, Hong Kong, avian genetics, mice, inbred BALB c, molecular sequence data, phylogeny, RNA viral analysis, viral core proteins genetics.

Massin, P., S. van der Werf, and N. Naffakh (2001). Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. Journal of Virology 75(11): 5398-404.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Human influenza A viruses replicate in the upper respiratory tract at a temperature of about 33 degrees C, whereas avian viruses replicate in the intestinal tract at a temperature close to 41 degrees C. In the present study, we analyzed the influence of low temperature (33 degrees C) on RNA replication of avian and human viruses in cultured cells. The kinetics of replication of the NP segment were similar at 33 and 37 degrees C for the human A/Puerto-Rico/8/34 and A/Sydney/5/97 viruses, whereas replication was delayed at 33 degrees C compared to 37 degrees C for the avian A/FPV/Rostock/34 and A/Mallard/NY/6750/78 viruses. Making use of a genetic system for the in vivo reconstitution of functional ribonucleoproteins, we observed that the polymerase complexes derived from avian viruses but not human viruses exhibited cold sensitivity in mammalian cells, which was determined mostly by residue 627 of PB2. Our results suggest that a reduced ability of the polymerase complex of avian viruses to ensure replication of the viral genome at 33 degrees C could contribute to their inability to grow efficiently in humans.

            Descriptors:  influenza A virus avian metabolism, human metabolism, RNA viral metabolism, viral proteins metabolism, cell line, mutation, viral genetics, temperature, time factors, transcription, genetic, viral proteins genetics, virus replication.

Matrosovich, M., A. Tuzikov, N. Bovin, A. Gambaryan, A. Klimov, M.R. Castrucci, I. Donatelli, and Y. Kawaoka (2000). Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. Journal of Virology 74(18): 8502-12.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Interspecies transmission of influenza A viruses circulating in wild aquatic birds occasionally results in influenza outbreaks in mammals, including humans. To identify early changes in the receptor binding properties of the avian virus hemagglutinin (HA) after interspecies transmission and to determine the amino acid substitutions responsible for these alterations, we studied the HAs of the initial isolates from the human pandemics of 1957 (H2N2) and 1968 (H3N2), the European swine epizootic of 1979 (H1N1), and the seal epizootic of 1992 (H3N3), all of which were caused by the introduction of avian virus HAs into these species. The viruses were assayed for their ability to bind the synthetic sialylglycopolymers 3'SL-PAA and 6'SLN-PAA, which contained, respectively, 3'-sialyllactose (the receptor determinant preferentially recognized by avian influenza viruses) and 6'-sialyl(N-acetyllactosamine) (the receptor determinant for human viruses). Avian and seal viruses bound 6'SLN-PAA very weakly, whereas the earliest available human and swine epidemic viruses bound this polymer with a higher affinity. For the H2 and H3 strains, a single mutation, 226Q-->L, increased binding to 6'SLN-PAA, while among H1 swine viruses, the 190E-->D and 225G-->E mutations in the HA appeared important for the increased affinity of the viruses for 6'SLN-PAA. Amino acid substitutions at positions 190 and 225 with respect to the avian virus consensus sequence are also present in H1 human viruses, including those that circulated in 1918, suggesting that substitutions at these positions are important for the generation of H1 human pandemic strains. These results show that the receptor-binding specificity of the HA is altered early after the transmission of an avian virus to humans and pigs and, therefore, may be a prerequisite for the highly effective replication and spread which characterize epidemic strains.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian metabolism, receptors, virus metabolism,  amino acid sequence, amino acid substitution, disease outbreaks, ducks virology, hemagglutinin glycoproteins, influenza virus chemistry, avian isolation and purification, models, molecular, molecular sequence data, mutation, missense, phylogeny, protein binding, seals virology, sequence alignment, sialic acids metabolism, species specificity, swine virology.

Matrosovich, M., N. Zhou, Y. Kawaoka, and R. Webster (1999). The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties. Journal of Virology 73(2): 1146-55.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In 1997, 18 confirmed cases of human influenza arising from multiple independent transmissions of H5N1 viruses from infected chickens were reported from Hong Kong. To identify possible phenotypic changes in the hemagglutinin (HA) and neuraminidase (NA) of the H5 viruses during interspecies transfer, we compared the receptor-binding properties and NA activities of the human and chicken H5N1 isolates from Hong Kong and of H5N3 and H5N1 viruses from wild aquatic birds. All H5N1 viruses, including the human isolate bound to Sia2-3Gal-containing receptors but not to Sia2-6Gal-containing receptors. This finding formally demonstrates for the first time that receptor specificity of avian influenza viruses may not restrict initial avian-to-human transmission. The H5N1 chicken viruses differed from H5 viruses of wild aquatic birds by a 19-amino-acid deletion in the stalk of the NA and the presence of a carbohydrate at the globular head of the HA. We found that a deletion in the NA decreased its ability to release the virus from cells, whereas carbohydrate at the HA head decreased the affinity of the virus for cell receptors. Comparison of amino acid sequences from GenBank of the HAs and NAs from different avian species revealed that additional glycosylation of the HA and a shortened NA stalk are characteristic features of the H5 and H7 chicken viruses. This finding indicates that changes in both HA and NA may be required for the adaptation of influenza viruses from wild aquatic birds to domestic chickens and raises the possibility that chickens may be a possible intermediate host in zoonotic transmission.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian metabolism, human metabolism, alpha globulins metabolism, amino acid sequence, carbohydrates metabolism, chickens, fowl plague virology, Hong Kong, horseradish peroxidase metabolism, influenza veterinary, influenza virology, avian classification, avian isolation and purification, human classification, human isolation and purification, molecular sequence data, neuraminidase metabolism, ovomucin metabolism, phenotype, receptors, virus metabolism, sequence homology, amino acid.

Matrosovich, M.N., A.S. Gambaryan, S. Teneberg, V.E. Piskarev, S.S. Yamnikova, D.K. Lvov, J.S. Robertson, and K.A. Karlsson (1997). Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site. Virology 233(1): 224-234.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Avian influenza virus strains representing most hemagglutinin (HA) subtypes were compared with human influenza A (H1N1, H3N2) and B virus isolates, including those with no history of passaging in embryonated hen's eggs, for their ability to bind free N-acetylneuraminic acid (Neu5Ac) and sialyloligosaccharides in a competitive binding assay and to attach to gangliosides in a solid-phase adsorption assay. The avian viruses, irrespective of their HA subtype, showed a higher affinity for sialyl-3-lactose and the other Neu5Ac2-3Gal-terminated oligosaccharides and a lower affinity for sialyl-6-lactose than for free Neu5Ac, indicative of specific interactions between the HA and the 3-linked Gal and poor accommodation of 6-linked Gal in the avian receptor-binding site (RBS). Human H1 and H3 strains, by contrast, were unable to bind to 3-linked Gal, interacting instead with the asialic portion of sialyl-6-(N-acetyllactosamine). Different parts of this moiety were recognized by H3 and H1 subtype viruses (Gal and GlcNAc, respectively). Comparison of the HA amino acid sequences revealed that residues in positions 138, 190, 194, 225, 226, and 228 are conserved in the avian RBS, while the human HAs harbor substitutions at these positions, A characteristic feature of avian viruses was their binding to Neu5Ac2-3Gal-containing gangliosides. This property of avian precursor viruses was preserved in early human H3 isolates, but was gradually lost with further circulation of the H3 HA in humans. Consequently, later human H3 isolates, as well as H1 and type B human strains, were unable to bind to short Neu5Ac2-3Gal-terminated gangliosides, an incompatibility that correlated with higher glycosylation of the HA globular head of human viruses. Our results suggest that the RBS is highly conserved among HA subtypes of avian influenza virus, while that of human viruses displays distinctive genotypic and phenotypic variability.

            Descriptors:  biochemistry and molecular biophysics, evolution and adaptation, genetics, infection, microbiology, avian influenza A virus, biochemistry and biophysics, conservation, gangliosides, genotypic variability, hemagglutinin receptor binding site, hemagglutinin subtypes, human influenza A virus, human influenza B virus, H1N1 subtype, H3N2 subtype, infection phenotypic variability, sialyloligosaccharides.

Matrosovich, M.N., S. Krauss, and R.G. Webster ( 2001). H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity. Virology 281(2): 156-62.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus avian metabolism, poultry virology, receptors, virus metabolism, amino acid substitution, Asia, binding sites, fowl plague transmission, fowl plague virology, hemagglutinin glycoproteins, influenza virus genetics, hemagglutinin glycoproteins, influenza virus metabolism, avian classification, avian genetics, human classification, human genetics, human metabolism, mutation, neuraminidase genetics, neuraminidase metabolism, phylogeny, viral envelope proteins genetics, viral envelope proteins metabolism.

Matrosovich, M.N., T.Y. Matrosovich, T. Gray, N.A. Roberts, and H.D. Klenk (2004). Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proceedings of the National Academy of Sciences of the United States of America 101(13): 4620-4.  ISSN: 0027-8424.

            NAL Call Number:  500 N21P

            Abstract:  The recent human infections caused by H5N1, H9N2, and H7N7 avian influenza viruses highlighted the continuous threat of new pathogenic influenza viruses emerging from a natural reservoir in birds. It is generally believed that replication of avian influenza viruses in humans is restricted by a poor fit of these viruses to cellular receptors and extracellular inhibitors in the human respiratory tract. However, detailed mechanisms of this restriction remain obscure. Here, using cultures of differentiated human airway epithelial cells, we demonstrated that influenza viruses enter the airway epithelium through specific target cells and that there were striking differences in this respect between human and avian viruses. During the course of a single-cycle infection, human viruses preferentially infected nonciliated cells, whereas avian viruses as well as the egg-adapted human virus variant with an avian virus-like receptor specificity mainly infected ciliated cells. This pattern correlated with the predominant localization of receptors for human viruses (2-6-linked sialic acids) on nonciliated cells and of receptors for avian viruses (2-3-linked sialic acids) on ciliated cells. These findings suggest that although avian influenza viruses can infect human airway epithelium, their replication may be limited by a nonoptimal cellular tropism. Our data throw light on the mechanisms of generation of pandemic viruses from their avian progenitors and open avenues for cell level-oriented studies on the replication and pathogenicity of influenza virus in humans.

            Descriptors:  influenza A virus, avian pathogenicity, human pathogenicity, respiratory mucosa microbiology, bronchi, cell line, dogs, avian isolation and purification, avian physiology, human isolation and purification, human physiology, kidney, lectins, microscopy, confocal, nasal mucosa microbiology, sialic acids analysis, trachea.

Matrosovich, M.N., T.Y. Matrosovich, T. Gray, N.A. Roberts, and H.D. Klenk (2004). Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. Journal of Virology 78(22): 12665-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza virus neuraminidase (NA) plays an essential role in release and spread of progeny virions, following the intracellular viral replication cycle. To test whether NA could also facilitate virus entry into cell, we infected cultures of human airway epithelium with human and avian influenza viruses in the presence of the NA inhibitor oseltamivir carboxylate. Twenty- to 500-fold less cells became infected in drug-treated versus nontreated cultures (P < 0.0001) 7 h after virus application, indicating that the drug suppressed the initiation of infection. These data demonstrate that viral NA plays a role early in infection, and they provide further rationale for the prophylactic use of NA inhibitors.

            Descriptors:  bronchi virology, nasal mucosa virology, neuraminidase physiology, orthomyxoviridae physiology, trachea virology, acetamides pharmacology, orthomyxoviridae enzymology.

Matsuoka, Y., H. Chen, N. Cox, K. Subbarao, J. Beck, and D. Swayne (2003). Safety evaluation in chickens of candidate human vaccines against potential pandemic strains of influenza. Avian Diseases 47(Special Issue): 926-930.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Two candidate formalin-inactivated vaccines, made from high-growth reassortant viruses with the HA and NA genes from avian viruses in a background of genes derived from A/Puerto Rico/8/34 (PR8), were prepared against H5N1 and H9N2 subtypes (designated as H5N1/PR8 and H9N2/PR8, respectively). These viruses bear the genotypes, antigenicity, and attenuation in mouse models that are desirable in candidate vaccines. The pathogenicity of the newly generated avian-human reassortant vaccine viruses was also evaluated in chickens. Neither H5N1/PR8 nor H9N2/PR8 were highly pathogenic for chickens. No clinical signs, gross legions, or histological lesions were observed in chickens that were administered H5N1/PR8 either intranasally (i.n.) or intravenously (i.v.), and virus was not detected in oropharyngeal or cloacal swabs. When H9N2/PR8 was administered i.n., no clinical signs, gross lesions, or histological lesions were observed and no virus was detected in cloacal swabs. However, virus was isolated at low titer from oropharyngeal swabs of all eight chickens. Although no clinical signs were observed when H9N2/PR8 was administered i.v., mild tracheitis was seen in one of two chickens. Moderate amounts of antigen were observed in tracheal respiratory epithelium, and low titers of virus were recovered from oropharyngeal and cloacal swabs of some chickens. In summary, both reassortant vaccine viruses replicated poorly in chickens. These studies suggest that these candidate vaccine viruses carry a low risk of transmission to chickens.

            Descriptors:  epidemiology, infection, avian influenza, infectious disease, prevention and control, respiratory system disease, viral disease.

Matsuura, Y., R. Yanagawa, and H. Noda (1979). Experimental infection of mink with influenza A viruses. Brief report. Archives of Virology 62(1): 71-6.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Mink were found to be susceptible to the intranasal inoculation of human, swine, equine and avian influenza A viruses. The viruses were recovered until the 7th post inoculation (p.i.) day from the respiratory tract. The inoculated mink showed antibody response against these viruses. Contact infection in mink with A/Kumamoto/22/77 (H3N2) was possible.

            Descriptors:  influenza A virus pathogenicity, orthomyxoviridae infections microbiology, antibodies, viral biosynthesis, disease models, animal, hemagglutination inhibition tests, influenza A virus immunology, influenza A virus isolation and purification, orthomyxoviridae infections immunology, orthomyxoviridae infections transmission, respiratory system microbiology.

McManus, K. (2004). Asian avian influenza--a call to action. Australian Veterinary Journal 82(3): 135.  ISSN: 0005-0423.

            NAL Call Number:  41.8 Au72

            Descriptors:  chickens, disease outbreaks veterinary, avian influenza, prevention and control, southeastern Asia, epidemiology, disease outbreaks prevention and control, influenza A virus.

Melville, D.S. and K.F. Shortridge (2004). Influenza: time to come to grips with the avian dimension. Lancet Infectious Diseases 4(5): 261-2.  ISSN: 1473-3099.

            Descriptors:  disease outbreaks prevention and control, avian influenza epidemiology, avian influenza prevention and control, zoonoses epidemiology, animal husbandry methods, southeastern Asia epidemiology, chickens, ducks.

Meslin, F.X., K. Stohr, and D. Heymann (2000). Public health implications of emerging zoonoses. Revue Scientifique Et Technique Office International Des Epizooties 19(1): 310-7.  ISSN: 0253-1933.

            NAL Call Number:  SF781.R4

            Abstract:  Many new, emerging and re-emerging diseases of humans are caused by pathogens which originate from animals or products of animal origin. A wide variety of animal species, both domestic and wild, act as reservoirs for these pathogens, which may be viruses, bacteria or parasites. Given the extensive distribution of the animal species affected, the effective surveillance, prevention and control of zoonotic diseases pose a significant challenge. The authors describe the direct and indirect implications for public health of emerging zoonoses. Direct implications are defined as the consequences for human health in terms of morbidity and mortality. Indirect implications are defined as the effect of the influence of emerging zoonotic disease on two groups of people, namely: health professionals and the general public. Professional assessment of the importance of these diseases influences public health practices and structures, the identification of themes for research and allocation of resources at both national and international levels. The perception of the general public regarding the risks involved considerably influences policy-making in the health field. Extensive outbreaks of zoonotic disease are not uncommon, especially as the disease is often not recognised as zoonotic at the outset and may spread undetected for some time. However, in many instances, the direct impact on health of these new, emerging or re-emerging zoonoses has been small compared to that of other infectious diseases affecting humans. To illustrate the tremendous indirect impact of emerging zoonotic diseases on public health policy and structures and on public perception of health risks, the authors provide a number of examples, including that of the Ebola virus, avian influenza, monkeypox and bovine spongiform encephalopathy. Recent epidemics of these diseases have served as a reminder of the existence of infectious diseases and of the capacity of these diseases to occur unexpectedly in new locations and animal species. The need for greater international co-operation, better local, regional and global networks for communicable disease surveillance and pandemic planning is also illustrated by these examples. These diseases have contributed to the definition of new paradigms, especially relating to food safety policies and more generally to the protection of public health. Finally, the examples described emphasise the importance of intersectorial collaboration for disease containment, and of independence of sectorial interests and transparency when managing certain health risks.

            Descriptors:  communicable diseases, emerging epidemiology, disease outbreaks prevention and control, public health, zoonoses epidemiology, zoonoses etiology, communicable diseases, emerging prevention and control, communicable diseases, emerging transmission, international cooperation, morbidity, risk factors, world health.

Mohammad Yousaf (2004). Avian influenza outbreak hits the industry again. World Poultry 20(3): 22-25.  ISSN: 1388-3119.

            NAL Call Number:  SF481.M54

            Descriptors:  disease control, disease prevention, disease surveys, disease transmission, epidemiology, clinical aspects, diagnostic techniques, outbreaks, pathogenicity, poultry industry, public health, World Health Organization, zoonoses, human diseases, avian influenza virus.

Mohan, R., Y.M. Saif, G.A. Erickson, G.A. Gustafson, and B.C. Easterday (1981). Serologic and epidemiologic evidence of infection in turkeys with an agent related to the swine influenza virus. Avian Diseases 25(1): 11-6.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Descriptors:  influenza veterinary, influenza A virus, porcine immunology, influenza A virus immunology, poultry diseases epidemiology, turkeys,  antibodies, viral analysis, hemagglutination tests veterinary, immunodiffusion veterinary, influenza diagnosis, influenza epidemiology, avian immunology, poultry diseases diagnosis.

Molibog, E.V., T.V. Pysina, and A.S. Gorbunova ( 1968). Sootnoshenie mezhdu eliuikuiushchei i neiraminidaznoi aktivost'iu virusov gruppa tipa A cheloveka, mlekopitaiushchikh i ptits. [Relationship between eluting and neuraminidase activity of human, mammalian and avian influenza type A viruses]. Voprosy Virusologii 13(5):  623-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  neuraminidase analysis, orthomyxoviridae enzymology, orthomyxoviridae physiology.

Monto, A.S. (2005). The threat of an avian influenza pandemic. New England Journal of Medicine 352(4): 323-5.  ISSN: 1533-4406.

            NAL Call Number:  448.8 N442

            Descriptors:  acetamides therapeutic use, antiviral agents therapeutic use, disease outbreaks prevention and control, influenza epidemiology, influenza transmission, influenza A virus, avian influenza classification, avian influenza genetics, avian influenza pathogenicity, birds, disease transmission prevention and control, genome, viral, influenza drug therapy, avian influenza transmission, avian influenza virology, neuraminidase antagonists and inhibitors, neuraminidase metabolism, virulence, zoonoses transmission, zoonoses virology.

Moore, J.T., L.M. Spence, T.D. Sanders, and A.K. Adams (1999). Human influenza: viral mutations and altered tropisms. Clinical Laboratory Science Journal of the American Society for Medical Technology 12(2): 67-9.  ISSN: 0894-959X.

            NAL Call Number:  RB37.A1C5

            Abstract:  Influenza is a virus that is capable of causing a pandemic of the human race. Influenza has the ability to infect humans by mutating and altering its pathogenic characteristics. Efforts must be made worldwide to educate people about the possibilities of a potential outbreak. Awareness of optimal conditions which could lead to viral mutation and human to human transmission of a neogenetic strain of influenza appears to be a key deterrent against future cases.

            Descriptors:  influenza genetics, influenza transmission, influenza A virus genetics, mutation, adolescent, adult, birds, child, preschool, disease outbreaks, Hong Kong epidemiology, infant, influenza physiopathology, influenza virology, influenza A virus avian genetics, middle aged, species specificity.

Morse, S.S. (2004). Factors and determinants of disease emergence. Revue Scientifique Et Technique Office International Des Epizooties 23(2): 443-51.  ISSN: 0253-1933.

            NAL Call Number:  SF781.R4

            Abstract:  Emerging infectious diseases can be defined as infections that have newly appeared in a population or are rapidly increasing in incidence or geographic range. Many of these diseases are zoonoses, including such recent examples as avian influenza, severe acute respiratory syndrome, haemolytic uraemic syndrome (a food-borne infection caused by certain strains of Escherichia coli) and probably human immunodeficiency virus/acquired immune deficiency syndrome. Specific factors precipitating the emergence of a disease can often be identified. These include ecological, environmental or demographic factors that place people in increased contact with the natural host for a previously unfamiliar zoonotic agent or that promote the spread of the pathogen. These factors are becoming increasingly prevalent, suggesting that infections will continue to emerge and probably increase. Strategies for dealing with the problem include focusing special attention on situations that promote disease emergence, especially those in which animals and humans come into contact, and implementing effective disease surveillance and control.

            Descriptors:  epidemiology, infection, public health, vector biology, veterinary medicine, SARS, severe acute respiratory syndrome, haemolytic uraemic syndrome, Escherichia coli, control, demographic factors, disease emergence, disease surveillance, ecological factors, environmental factors, geographic range, zoonosis.

Mounts, A.W., H. Kwong, H.S. Izurieta, Y. Ho, T. Au, M. Lee, C. Buxton Bridges, S.W. Williams, K.H. Mak, J.M. Katz, W.W. Thompson, N.J. Cox, and K. Fukuda (1999). Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997. Journal of Infectious Diseases 180(2): 505-8.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  In May 1997, a 3-year-old boy in Hong Kong died of a respiratory illness related to influenza A (H5N1) virus infection, the first known human case of disease from this virus. An additional 17 cases followed in November and December. A case-control study of 15 of these patients hospitalized for influenza A (H5N1) disease was conducted using controls matched by age, sex, and neighborhood to determine risk factors for disease. Exposure to live poultry (by visiting either a retail poultry stall or a market selling live poultry) in the week before illness began was significantly associated with H5N1 disease (64% of cases vs. 29% of controls, odds ratio, 4.5, P=.045). By contrast, travel, eating or preparing poultry products, recent exposure to persons with respiratory illness, including persons with known influenza A (H5N1) infection, were not associated with H5N1 disease.

            Descriptors:  influenza etiology, influenza A virus avian isolation and purification, adolescent, adult, case control studies, child, preschool, Hong Kong, infant, influenza virology, matched pair analysis, middle aged, poultry,  risk factors.

Murakami, Y., K. Nerome, Y. Yoshioka, S. Mizuno, and A. Oya (1988). Difference in growth behavior of human, swine, equine, and avian influenza viruses at a high temperature. Archives of Virology 100(3-4): 231-44.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Growth characteristics of a wide range of influenza A viruses from different mammals and bird species were examined in an established line of canine kidney (MDCK) cells at an ordinary (37 degrees C) and a high temperature (42 degrees C). Although all viruses employed in the present study possessed a capability of replicating at 37 degrees C, virus growth at 42 degrees C showed considerable variation and reflected differences in the natural hosts of the isolates. All reference strains and isolates from bird species grew well in the MDCK cells maintained at 42 degrees C, but human viruses did not, showing an asymmetrical growth behavior. In contrast to this, growth of swine and equine viruses showed growth characteristics intermediate between human and avian viruses. Of the two swine viruses examined, replication of one strain occurred equally well at both temperatures and another failed to grow at 42 degrees C. Similarly, two of the three equine viruses tested belonging to H3N8 antigenic subtypes grew at 42 degrees C. However, the results obtained from comparison of plaque sizes and growth curves indicated that the replication of the above swine and equine viruses was restricted under a stringent temperature when compared to avian viruses. The detailed analysis of cloned viruses revealed that some of the swine and equine viruses contained two variants which are readily distinguished by growth behavior at 42 degrees C. Genome analysis of parental and virus clones by oligonucleotide mapping and migration profiles of RNA segments did not detect any differences among the above variants exhibiting the asymmetrical growth characteristics at 42 degrees C.

            Descriptors:  influenza A virus avian growth and development, human growth and development, influenza A virus growth and development, cell line, genes viral, horses, avian genetics, human genetics, porcine genetics, porcine growth and development, influenza A virus genetics, plaque assay, RNA viral genetics, temperature.

Murphy, B.R., A.J. Buckler White, W.T. London, J. Harper, E.L. Tierney, N.T. Miller, L.J. Reck, R.M. Chanock, and V.S. Hinshaw (1984). Avian-human reassortant influenza A viruses derived by mating avian and human influenza A viruses.  Journal of Infectious Diseases 150(6): 841-50.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Reassortant influenza A viruses were produced by mating an avian virus (A/Mallard/NY/78, A/Mallard/Alberta/78, or A/Pintail/Alberta/79) with a wild-type human influenza A virus. From each mating a reassortant virus was obtained that contained the genes coding for the hemagglutinin and neuraminidase surface antigens of the human influenza A wild-type virus and the six other RNA segments ("internal genes") of the avian influenza A virus parent. The avian-human reassortant influenza viruses produced resembled their avian virus parent in that they produced plaques on MDCK monolayers at 42 C, a temperature restrictive for the human influenza viruses. In the trachea of squirrel monkeys, each avian-human reassortant influenza virus was as restricted in its replication as was its avian influenza virus parent. Thus, one or more of the six internal genes of each avian parent virus was responsible for restriction of the reassortant virus in monkeys. The A/Washington/80 X A/Mallard/NY/78 reassortant virus retained its phenotype of restricted replication in monkeys after five serial passages in vivo. It also failed to transmit to cagemates or induce resistance to wild-type virus challenge, and it did not initiate a systemic or enteric infection. These findings form the basis for evaluation of these attenuated avian-human reassortant influenza A viruses as live attenuated vaccines for humans.

            Descriptors:  crosses, genetic, influenza A virus avian genetics, human genetics, neuraminidase genetics, chickens, child, ducks, hemagglutinins viral genetics, immunization, avian physiology, human physiology, saimiri, virus replication.

Murphy, B.R., A.J. Buckler White, W.T. London, and M.H. Snyder (1989). Characterization of the M protein and nucleoprotein genes of an avian influenza A virus which are involved in host range restriction in monkeys. Vaccine 7(6): 557-61.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  A reassortant virus possessing RNA segment 7, which codes for the M1 and M2 proteins, of the avian influenza A/Mallard/New York/6750/78 (H2N2) virus and the other seven RNA segments of the human influenza A/Udorn/307/72 (H3N2) virus had been shown previously to be markedly restricted in replication in the respiratory tract of squirrel monkeys. In contrast, a reassortant possessing segment 7 of another avian influenza virus, A/Pintail/Alberta/119/79 (H4N6), and the seven other RNA segments from the A/Udorn/72 virus was not restricted. The nucleotide and deduced amino acid sequence of the RNA segment 7 of each virus was determined to identify the structural basis for the attenuation phenotype specified by RNA segment 7 of the A/Mallard/78 virus. Analysis of the deduced amino acid sequences revealed only two amino acid differences in the M1 protein and one difference in the M2 protein, suggesting that the attenuation phenotype of a reassortant virus possessing segment 7 of the A/Mallard/78 virus may be specified by one to three amino acids. Reassortant viruses possessing RNA segment 6, which codes for the nucleoprotein, of either avian influenza virus and the other seven RNA segments of a human influenza virus were also restricted in replication in squirrel monkeys. A comparison of the deduced amino acid sequences of the two avian nucleopeoteins demonstrated only three amino acid differences indicating that these two avian viruses possess NP genes that are highly related. The high degree of relatedness of both the NP and M proteins of these two avian viruses contrasts with their divergent surface antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

            Descriptors:  genes viral, influenza A virus avian genetics, nucleoproteins genetics, viral core proteins, viral matrix proteins genetics, viral proteins genetics, amino acid sequence, base sequence, human genetics, RNA viral analysis, saimiri, virus replication.

Murphy, B.R., M.L. Clements, E.L. Tierney, R.E. Black, J. Stienberg, and R.M. Chanock (1985). Dose response of influenza A/Washington/897/80 (H3N2) avian-human reassortant virus in adult volunteers. Journal of Infectious Diseases 152(1): 225-9.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  antibodies, viral biosynthesis, influenza A virus avian immunology, human immunology, influenza vaccine immunology, adult, dose response relationship, immunologic, influenza microbiology, influenza transmission, avian genetics, human genetics, recombination, genetic, vaccination, vaccines, attenuated.

Murphy, B.R., V.S. Hinshaw, D.L. Sly, W.T. London, N.T. Hosier, F.T. Wood, R.G. Webster, and R.M. Chanock (1982). Virulence of avian influenza A viruses for squirrel monkeys. Infection and Immunity 37(3): 1119-26.  ISSN: 0019-9567.

            NAL Call Number:  QR1.I57

            Descriptors:  cebidae microbiology, influenza A virus avian pathogenicity, saimiri microbiology, cell line, dogs, ducks microbiology, ferrets microbiology, hamsters, avian growth and development, human growth and development, lung microbiology, mesocricetus microbiology, plaque assay, turbinates microbiology, virus replication.

Murphy, B.R., D.L. Sly, E.L. Tierney, N.T. Hosier, J.G. Massicot, W.T. London, R.M. Chanock, R.G. Webster, and V.S. Hinshaw (1982). Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys. Science 218(4579): 1330-2.  ISSN: 0036-8075.

            NAL Call Number:  470 Sci2

            Abstract:  An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication is squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistant to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.

            Descriptors:  influenza A virus avian genetics, human genetics, influenza vaccine immunology, antigens, surface genetics, epitopes genetics, epitopes immunology, hamsters, hemagglutinins genetics, hemagglutinins immunology, neuraminidase genetics, neuraminidase immunology, saimiri, vaccines, attenuated immunology.

Naffakh, N., J.C. Manuguerra, and S. Van der Werf (2002). Grippe: Zoonose et transmission inter-especes.  [Influenza viruses: Zoonosis and interspecies transmission]. Virologie Montrouge 6(Special): S73-S82.  ISSN: 1267-8694.

            Abstract:  Influenza A viruses have been isolated from a wide range of species. Aquatic birds, in which all 15 hemagglutinin subtypes have been found, are believed to be the reservoir of influenza A viruses from which new virus subtypes can episodically be transmitted to new hosts. Generally, avian influenza viruses replicate poorly in humans. However, adaptation of an avian virus to the human host may occur either through genetic reassortment or following direct transmission, and may result in influenza pandemics, as has been the case in 1918, 1957 and 1968. Several observations suggest that pigs, in which both avian and human influenza viruses replicate, are involved as a link and a mixing vessel in interspecies transmissions of influenza viruses. In addition, domestic poultry seem to serve as intermediate hosts for the acquisition of determinants that increase the potential of transmission of influenza viruses to mammals. The molecular bases for the host-specificity of human or avian influenza A viruses are not fully understood. The hemagglutinin and neuraminidase are considered as possible determinants of host-restriction because of different receptor specificities. In addition, genetic studies have indicated that gene segments encoding internal proteins, and especially the PB2 segment, harbor host-range determinants. This notion was strengthened by the fact that the six internal genes of avian H5N1 and H9N2 viruses that were responsible for respiratory disease in humans in Hong Kong in 1997 and 1999, respectively, were found to be very similar. However, the multiple genetic features of internal genes that contribute to host-specificity of influenza A viruses and to their potential for interspecies transmission, as well as the molecular mechanisms involved, are still to be understood.

            Descriptors:  biochemistry and molecular biophysics, infection, influenza, respiratory system disease, viral disease.

Naffakh, N., P. Massin, N. Escriou, B. Crescenzo Chaigne, and S. van der Werf (2000). Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses. Journal of General Virology 81(Pt. 5): 1283-91.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  In order to determine how efficiently the polymerase proteins derived from human and avian influenza A viruses can interact with each other in the context of a mammalian cell, a genetic system that allows the in vivo reconstitution of active ribonucleoproteins was used. The ability to achieve replication of a viral-like reporter RNA in COS-1 cells was examined with heterospecific mixtures of the core proteins (PB1, PB2, PA and NP) from two strains of human viruses (A/Puerto Rico/8/34 and A/Victoria/3/75), two strains of avian viruses (A/Mallard/NY/6750/78 and A/FPV/-Rostock/34), and a strain of avian origin (A/Hong Kong/156/97) that was isolated from the first human case of H5N1 influenza in Hong Kong in 1997. In accordance with published observations on reassortant viruses, PB2 amino acid 627 was identified as a major determinant of the replication efficiency of heterospecific complexes in COS-1 cells. Moreover, the results showed that replication of the viral-like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins. Furthermore, the PB1 and PB2 proteins from the A/Hong- Kong/156/97 virus exhibited intermediate properties with respect to the corresponding proteins from avian or human influenza viruses, suggesting that some molecular characteristics of PB1 and PB2 proteins might at least partially account for the ability of the A/Hong Kong/156/97 virus to replicate in humans.

            Descriptors:  influenza A virus avian genetics, influenza A virus human genetics, nucleoproteins, RNA replicase, viral core proteins genetics, viral core proteins metabolism, cos cells, chloramphenicol o acetyltransferase, cloning, molecular, DNA, complementary, DNA directed RNA polymerases genetics, DNA directed RNA polymerases metabolism, influenza A virus avian metabolism, influenza A virus human metabolism, molecular sequence data, plasmids genetics, sequence analysis, DNA, transcription, genetic, transfection, viral proteins genetics, viral proteins metabolism, virus replication.

Nagai, Y., K. Otsuki, N. Abe, Y. Kawaoka, H. Kida, T. Kurata, T. Sata, M. Tashiro, N. Yamaguchi, and H. Yoshikura (2004). [Round table discussion on highly pathogenic H5N1 avian influenza]. Uirusu Journal of Virology 54(1): 123-41.  ISSN: 0042-6857.

            Descriptors:  influenza A virus, avian pathogenicity, virulence, Asia epidemiology, disease outbreaks prevention and control, influenza epidemiology, influenza prevention and control, influenza transmission, influenza virology, avian influenza A virus classification, avian influenza A virus genetics, avian influenza A virus immunology, avian influenza epidemiology, avian influenza prevention and control, avian influenza transmission, avian influenza virology, poultry, receptors, virus physiology, viral vaccines, zoonoses epidemiology, zoonoses transmission, zoonoses virology.

Nakajima, K., E. Nobusawa, and S. Nakajima (1984). Genetic relatedness between A/Swine/Iowa/15/30(H1N1) and human influenza viruses. Virology 139(1): 194-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The nucleotide sequences of the M and NS1 genes of influenza virus A/Swine/Iowa/15/30 (A/SW/IW/30)(H1N1) were determined with cloned DNAs and compared with reported sequences of human and avian influenza viruses. A/SW/IW/30 virus was found to be closely similar to A/PR/8/34(H1N1) virus in the nucleotide sequences of the M and NS1 genes, the base differences between the two strains being 64 out of 1027 nucleotides in the M gene and 52 out of 740 in the NS1 gene. Based on the assumptions that these two viruses were derived from a common ancestor and that the rate of base changes per year was the same in man and in swine, it was estimated that the progenitor virus was in circulation during the period from 1915 to 1920. This estimation was compatible with the epidemiological findings suggesting that the progenitor of the swine influenza virus was the agent of the 1918 influenza pandemic. Furthermore, the M and NS1 gene sequences of A/FPV/Rostock/34(H7N6) virus were much closer to those of A/SW/IW/30 and A/PR/8/34 viruses than to A/duck/Alberta/60/76(H12N5) virus, but not as close as the A/SW/IW/30 virus was to A/PR/8/34 virus.

            Descriptors:  influenza A virus human genetics, influenza A virus, porcine genetics, influenza A virus genetics, base sequence, evolution, genes viral.

Nerome, K., Y. Kanegae, K.F. Shortridge, S. Sugita, and M. Ishida (1995). Genetic analysis of porcine H3N2 viruses originating in southern China. Journal of General Virology 76(Pt. 3): 613-24.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  From immunological and phylogenetic analyses of H3 influenza viruses isolated from pigs and ducks in the People's Republic of China (China), Hong Kong, Taiwan and Japan, between 1968 and 1982, we arrived at the following conclusions. The H3 haemagglutinin and N2 neuraminidase genes from swine isolates can be segregated into four mammalian lineages, including: (i) the earliest human strains; (ii) early swine strains including Hong Kong isolates from 1976-1977; (iii) an intermediate strain between the early swine and recent human strains; and (iv) recent human strains. In this study we found an unusual swine strain (sw/Hong Kong/127/82) belonging to the third lineage which behaved like those of the early swine-like lineage in the haemagglutination inhibition test; but neuraminidase inhibition profiles with monoclonal antibodies indicated that this virus is related to late human strains. On the basis of pairwise comparisons of complete or partial nucleotide sequences the genes encoding the three polymerase proteins (PB2, PB1, PA), the nucleoprotein, the membrane protein and possibly the nonstructural proteins of sw/Hong Kong/127/82 are of the swine H1N1 lineage, whereas genes encoding the two surface glycoproteins belong to the human H3N2 lineage. In contrast, all RNA segments of one swine isolate (sw/Hong Kong/81/78) are similar to those of recent human H3N2 viruses. This study indicated that frequent interspecies infections between human and swine hosts appeared to occur during 1976-82. Although the evolutionary rates of human (0.0122/site/year), swine (0.0127/site/year) and avian (0.0193/site/year) virus genes are similar when based upon synonymous substitutions, nonsynonymous substitutions indicated that viral genes derived from human and swine viruses evolved about three times faster (0.0026-0.0027/site/year) than those of avian viruses (0.0008/site/year). Furthermore, the evolutionary mechanism by which human and swine H3 haemagglutinin genes evolve at a similar rate, based on nonsynonymous substitutions, appeared to be quite different from previous evidence which showed that human H1 haemagglutinin genes evolved three times faster than those of swine viruses. However, comparison of the number of nonsynonymous substitutions in the antigenic sites (A-E) of haemagglutinin molecules demonstrated that swine viruses evolve at a rate that is about one fifth to one tenth that of human viruses, reflecting the conservative nature of the antigenic structure in the former.

            Descriptors:  evolution, genes viral genetics, hemagglutinins viral genetics, influenza A virus, porcine genetics, influenza A virus genetics, amino acid sequence, antibodies, monoclonal, antibodies, viral, antigenic variation genetics, China, hemagglutinins viral analysis, hemagglutinins viral immunology, Hong Kong, influenza A virus avian genetics, influenza A virus avian immunology, influenza A virus human genetics, influenza A virus human immunology, influenza A virus, porcine immunology, influenza A virus immunology, molecular sequence data, neuraminidase analysis, neuraminidase genetics, RNA viral genetics, sequence analysis, DNA, sequence homology, amino acid, sequence homology, nucleic acid, swine.

Nerome, K., Y. Yoshioka, C.A. Torres, A. Oya, P. Bachmann, K. Ottis, and R.G. Webster (1984). Persistence of Q strain of H2N2 influenza virus in avian species: antigenic, biological and genetic analysis of avian and human H2N2 viruses. Archives of Virology 81(3-4): 239-50.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The characteristics of an avian influenza virus were compared in detail with those of human Asian (H2N2) influenza viruses. Antigenic analysis by different antisera against H2N2 viruses and monoclonal antibodies to both the hemagglutinin and neuraminidase antigens showed that an avian isolate, A/duck/Munchen/9/79 contained hemagglutinin and neuraminidase subunits closely related to those of the early human H2N2 viruses which had been prevalent in 1957. However, this avian virus gave low HI titers with absorbed and non-absorbed antisera to different human H2N2 viruses isolated in 1957. Like human Q phase variant, such as A/RI/5-/57 (H2N2), hemagglutination of the above avian strain was not inhibited by the purified non-specific gamma-inhibitor from guinea pig serum. Growth behavior at restrictive temperature (42 degrees C) clearly differentiate the avian H2N2 virus from human influenza viruses, showing that the former virus grew well in MDCK cells at 42 degrees C but not the latters. Genomic analysis of these viruses revealed that the oligonucleotide map of H2N2 virus isolated from a duck was quite different from those of human H2N2 viruses from 1957 to 1967. The oligonucleotide mapping also indicated that different H2N2 influenza virus variants had co-circulated in humans in 1957.

            Descriptors:  influenza A virus avian immunology, influenza A virus human immunology, hemagglutinins viral immunology, influenza A virus avian genetics, influenza A virus human genetics, influenza A virus growth and development, neuraminidase immunology, RNA viral genetics.

Nestorowicz, A., Y. Kawaoka, W.J. Bean, and R.G. Webster (1987). Molecular analysis of the hemagglutinin genes of Australian H7N7 influenza viruses: role of passerine birds in maintenance or transmission? Virology 160(2): 411-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  In 1985 a fowl plague-like disease occurred in chickens in Lockwood, Victoria, Australia and caused high mortality. An H7N7 influenza virus was isolated from the chickens (A/Chicken/Victoria/1/85); additionally, an antigenically similar virus was isolated from starlings (A/Starling/Victoria/5156/85) and serological evidence of H7N7 virus infection was found in sparrows. Antigenic analysis with monoclonal antibodies to H7, oligonucleotide mapping of total vRNA, and sequence analysis of the HA genes established that the chicken and starling influenza viruses were closely related and probably came from the same source. There was high nucleotide sequence homology (95.3%) between the HA genes of A/Chick/Vic/85 and a fowl plague-like virus isolated from chickens in Victoria 9 years earlier [A/Fowl/Vic/76 (H7N7)]. The sequence homologies indicated that the A/Chick/Vic/85 and A/Fowl/Vic/76 were derived from a common recent ancestor, while another recent H7N7 virus, Seal/Mass/1/80 originated from a different evolutionary lineage. Experimental infection of chickens and starlings with A/Chick/Vic/1/85 (H7N7) was associated with high mortality (100%), transmission to contact birds of the same species, and virus in all organs. In sparrows one-third of the birds died after infection and virus was isolated from most organs; transmission to contact sparrows did not occur. In contrast, the H7N7 virus replicated in ducks and spread to contact ducks but caused no mortality. These studies establish that the host species plays a role in determining the virulence of avian influenza viruses, and provide the first evidence for transmission of virulent influenza viruses between domestic poultry and passerine birds. They support the hypothesis that potentially virulent H7N7 influenza viruses could be maintained in ducks where they cause no apparent disease and may sometimes spread to other wild birds and domestic poultry.

            Descriptors:  birds microbiology, hemagglutinins viral genetics, influenza A virus avian genetics, amino acid sequence, animals, wild microbiology, Australia, base sequence, chickens microbiology, disease reservoirs, genes viral, molecular sequence data, nucleotide mapping, RNA viral genetics, species specificity, virus replication.

Nettles, V.F., J.M. Wood, and R.G. Webster (1985). Wildlife surveillance associated with an outbreak of lethal H5N2 avian influenza in domestic poultry. Avian Diseases 29(3): 733-41.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Wildlife surveillance was conducted for influenza viruses in conjunction with the 1983-84 lethal H5N2 avian influenza epizootic in domestic poultry in Pennsylvania, New Jersey, Maryland, and Virginia. Virus-isolation attempts made on cloacal and tracheal swabs from 4,466 birds and small rodents within the quarantined areas and 1,511 waterfowl in nearby Maryland yielded only a single H5N2 isolate from a pen-raised chukar in Pennsylvania. Antibodies against hemagglutinin type 5 and/or neuraminidase type 2 were found in 33% of the aquatic birds tested; however, this finding could not be used to confirm previous H5N2 avian influenza virus activity because of the possibility of prior infections with multiple influenza subtypes. The low prevalence of lethal H5N2 avian influenza virus in wild birds and small rodents strongly indicated that these animals were not responsible for dissemination of the disease among poultry farms during the outbreak.

            Descriptors:  birds microbiology, disease outbreaks veterinary, fowl plague transmission, disease reservoirs microbiology, hemagglutinins viral analysis, neuraminidase analysis, orthomyxoviridae isolation and purification, paramyxoviridae isolation and purification, Pennsylvania.

Nguyen, D.C., T.M. Uyeki, S. Jadhao, T. Maines, M. Shaw, Y. Matsuoka, C. Smith, T. Rowe, X. Lu, H. Hall, X. Xu, A. Balish, A. Klimov, T.M. Tumpey, D.E. Swayne, L.P. Huynh, H.K. Nghiem, H.H. Nguyen, L.T. Hoang, N.J. Cox, and J.M. Katz (2005). Isolation and characterization of avian influenza viruses, including highly pathogenic H5N1, from poultry in live bird markets in Hanoi, Vietnam, in 2001. Journal of Virology 79(7): 4201-12.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Since 1997, outbreaks of highly pathogenic (HP) H5N1 and circulation of H9N2 viruses among domestic poultry in Asia have posed a threat to public health. To better understand the extent of transmission of avian influenza viruses (AIV) to humans in Asia, we conducted a cross-sectional virologic study in live bird markets (LBM) in Hanoi, Vietnam, in October 2001. Specimens from 189 birds and 18 environmental samples were collected at 10 LBM. Four influenza A viruses of the H4N6 (n = 1), H5N2 (n = 1), and H9N3 (n = 2) subtypes were isolated from healthy ducks for an isolation frequency of over 30% from this species. Two H5N1 viruses were isolated from healthy geese. The hemagglutinin (HA) genes of these H5N1 viruses possessed multiple basic amino acid motifs at the cleavage site, were HP for experimentally infected chickens, and were thus characterized as HP AIV. These HA genes shared high amino acid identities with genes of other H5N1 viruses isolated in Asia during this period, but they were genetically distinct from those of H5N1 viruses isolated from poultry and humans in Vietnam during the early 2004 outbreaks. These viruses were not highly virulent for experimentally infected ducks, mice, or ferrets. These results establish that HP H5N1 viruses with properties similar to viruses isolated in Hong Kong and mainland China circulated in Vietnam as early as 2001, suggest a common source for H5N1 viruses circulating in these Asian countries, and provide a framework to better understand the recent widespread emergence of HP H5N1 viruses in Asia.

            Descriptors:  avian influenza A virus classification, avian influenza A virus isolation and purification, avian influenza virology, poultry virology, viral antigens, chickens virology, ducks virology, molecular epidemiology, ferrets, geese virology, avian influenza A virus genetics, avian influenza A viruspathogenicity, mice, molecular sequence data, neuraminidase genetics, phylogeny, sequence analysis, serotyping, Vietnam, virulence.

Nicholson, K.G., A.E. Colegate, A. Podda, I. Stephenson, J. Wood, E. Ypma, and M.C. Zambon (2001). Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: A randomised trial of two potential vaccines against H5N1 influenza. Lancet 357(9272): 1937-1943.  ISSN: 0099-5355.

            NAL Call Number:  448.8 L22

            Abstract:  Background: In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat to human beings. A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines. Methods: 32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 mug haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination. Findings: The A/Duck/Singapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 mug doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 mug doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus. Interpretation: Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 mug haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.

            Descriptors:  infection, pharmacology, influenza, respiratory system disease, viral disease, antigenicity safety.

Nicholson, K.G., J.M. Wood, and M. Zambon (2003). Influenza. Lancet 362(9397): 1733-1745.  ISSN: 0099-5355.

            NAL Call Number:  448.8 L22

            Descriptors:  epidemiology, humans, infection, influenza, vaccination, clinical techniques, pandemic prevention.

Niculescu, I.T., E. Zilisteanu, L. Cretescu, M. Matepiuc, and V. Roman (1972). Relationship between human and animal infections with A2 /Hong Kong/68 - like strains of influenza virus. Archives Roumaines De Pathologie Experimentales Et De Microbiologie 31(4 Suppl): 545-52.  ISSN: 0004-0037.

            NAL Call Number:  448.3 Ar22

            Descriptors:  influenza epidemiology, orthomyxoviridae immunology, birds, cross reactions, influenza A virus avian immunology, influenza A virus human immunology, influenza A virus, porcine immunology, Romania, swine.

Ninomiya, A., A. Takada, K. Okazaki, K.F. Shortridge, and H. Kida (2002). Seroepidemiological evidence of avian H4, H5, and H9 influenza A virus transmission to pigs in southeastern China. Veterinary Microbiology 88(2): 107-14.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  Pig serum samples collected in southeastern China were examined for antibodies to influenza A viruses. Since the hemagglutination inhibition (HI) test does not accurately detect antibodies to the hemagglutinins (HAs) of "avian" influenza viruses, we utilized the neutralization (NT) test to detect subtype-specific antibodies to the HA of avian viruses in pig sera. Neutralizing antibodies to H1, H3, H4, and H5 influenza viruses were detected in the serum samples collected in 1977-1982 and 1998, suggesting that pigs in China have been sporadically infected with avian H4 and H5 viruses in addition to swine and human H1 and H3 viruses. Antibodies to H9 virus, on the other hand, were found only in the sera collected in 1998, not in those collected in 1977-1982, correlating with the recent spread in poultry and subsequent isolation of H9N2 viruses from pigs and humans in 1998. The present results indicate that avian influenza viruses have been transmitted to pig populations in southeastern China.

            Descriptors:  antibodies, viral blood, influenza veterinary, influenza A virus immunology, swine diseases epidemiology, China epidemiology, hemagglutination inhibition tests veterinary, hemagglutinins viral, influenza epidemiology, influenza transmission, influenza A virus avian immunology, influenza A virus human immunology, influenza A virus, porcine immunology, influenza A virus classification, neutralization tests veterinary, poultry, seroepidemiologic studies, specific pathogen free organisms, swine, swine diseases blood, swine diseases transmission, swine diseases virology.

Normile, D. (2005). Avian flu. First human case in Cambodia highlights surveillance shortcomings. Science 307(5712): 1027.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Descriptors:  influenza epidemiology, influenza virology, influenza A virus, avian, influenza, avian epidemiology, population surveillance, adult, southeastern Asia epidemiology, Cambodia epidemiology, disease outbreaks veterinary, influenza transmission, poultry.

Normile, D. (2004). Infectious diseases. Stopping Asia's avian flu: a worrisome third outbreak. Science 303(5657): 447.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Descriptors:  disease outbreaks veterinary, influenza virology, influenza A virus, avian classification, avian influenza pathogenicity, avian influenza epidemiology, avian virology, birds, chickens, China epidemiology, disease reservoirs, influenza epidemiology, influenza prevention and control, influenza transmission, avian influenza prevention and control, avian influenza transmission, Japan epidemiology, Korea epidemiology, Vietnam epidemiology.

Normile, D. and M. Enserink (2004). Infectious diseases. Avian influenza makes a comeback, reviving pandemic worries. Science 305(5682): 321.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Descriptors:  disease outbreaks veterinary, influenza epidemiology, influenza virology, influenza A virus, avian pathogenicity, avian influenza epidemiology, Asia epidemiology, birds, evolution, molecular, avian genetics, avian influenza virology, poultry, recombination, genetic.

Okazaki, K. (1983). Studies on susceptibility of mink to influenza viruses--serological evidence of human influenza virus infection in mink, contact infection of mink with avian influenza viruses, and application of mink for evaluation of influenza vaccine. Japanese Journal of Veterinary Research 31(2): 95.  ISSN: 0047-1917.

            NAL Call Number:  41.8 V6446

            Descriptors:  avian influenza virus, human influenza virus, mink, susceptibility, studies, serological evidence.

Okazaki, K., A. Takada, T. Ito, M. Imai, H. Takakuwa, M. Hatta, H. Ozaki, T. Tanizaki, T. Nagano, A. Ninomiya, V.A. Demenev, M.M. Tyaptirganov, T.D. Karatayeva, S.S. Yamnikova, D.K. Lvov, and H. Kida (2000). Precursor genes of future pandemic influenza viruses are perpetuated in ducks nesting in Siberia. Archives of Virology 145(5): 885-93.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Influenza A viruses of different subtypes were isolated from fecal samples of ducks in their nesting areas in Siberia in summer from 1996 to 1998. Phylogenetic analysis of the NP genes of the isolates in Siberia and those in Hokkaido, Japan on their flyway of migration from Siberia to the south in autumn revealed that they belong to the Eurasian lineage of avian influenza viruses. It is noted that the genes of the isolates in Siberia are closely related to those of H5N1 influenza virus strains isolated from chickens and humans in Hong Kong in 1997 as well as to those of isolates from domestic birds in southern China. The results indicate that influenza viruses perpetuated in ducks nesting in Siberia should have contributed genes in the emergence of the H5N1 virus in Hong Kong. Vaccine prepared from avirulent A/duck/Hokkaido/4/96 (H5N3) influenza virus was potent enough to protect mice from challenge with lethal dose of the pathogenic H5N1 virus [19]. Intensive surveillance study of aquatic birds especially in Siberia is, therefore, stressed to provide information on the future pandemic influenza virus strains and for vaccine preparation.

            Descriptors:  ducks virology, genes viral, influenza A virus avian genetics, base sequence, DNA primers genetics, disease reservoirs, fowl plague immunology, fowl plague prevention and control, influenza A virus avian classification, influenza A virus avian pathogenicity, influenza vaccine pharmacology, Japan, mice, nucleoproteins genetics,  phylogeny, poultry, Siberia, viral proteins genetics.

Okazaki, K., R. Yanagawa, and H. Kida (1983). Contact infection of mink with 5 subtypes of avian influenza virus. Archives of Virology 77(2-4): 265-269.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Descriptors:  avian influenza virus, transmission, epidemiology, host range, mink.

Olofsson, S., U. Kumlin, K. Dimock, and N. Arnberg (2005). Avian influenza and sialic acid receptors: more than meets the eye? Lancet Infectious Diseases 5(3): 184-8.  ISSN: 1473-3099.

            Abstract:  Given our recent discoveries that the ocular human pathogens adenovirus serotype 37 and enterovirus serotype 70 use sialic acid linked to galactose via alpha2,3 glycosidic bonds as a cellular receptor, we propose that the presence of this receptor in the eye also explains the ocular tropism exhibited by zoonotic avian influenza A viruses such as subtype H5N1 in Hong Kong in 1997, H7N7 in the Netherlands in 2003, H7N2 in the USA in 2003, and H7N3 in Canada in 2004. We also draw attention to the implications this hypothesis may have for epizootic and zoonotic influenza, and the initiation of future pandemics.

            Descriptors:  Adenoviridae classification, eye diseases virology, avian influenza pathology, cell surface physiology receptors, zoonoses virology, Adenoviridae pathology, birds, avian influenza epidemiology, avian influenza transmission, serotyping, zoonoses transmission, sialic acid.

Olsen, C.W. (2002). The emergence of novel swine influenza viruses in North America. Virus Research  85(2): 199-210.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  Since 1997, novel viruses of three different subtypes and five different genotypes have emerged as agents of influenza among pigs in North America. The appearance of these viruses is remarkable because there were no substantial changes in the overall epidemiology of swine influenza in the United States and Canada for over 60 years prior to this time. Viruses of the classical H1N1 lineage were virtually the exclusive cause of swine influenza from the time of their initial isolation in 1930 through 1998. Antigenic drift variants of these H1N1 viruses were isolated in 1991-1998, but a much more dramatic antigenic shift occurred with the emergence of H3N2 viruses in 1997-1998. In particular, H3N2 viruses with genes derived from human, swine and avian viruses have become a major cause of swine influenza in North America. In addition, H1N2 viruses that resulted from reassortment between the triple reassortant H3N2 viruses and classical H1N1 swine viruses have been isolated subsequently from pigs in at least six states. Finally, avian H4N6 viruses crossed the species barrier to infect pigs in Canada in 1999. Fortunately, these H4N6 viruses have not been isolated beyond their initial farm of origin. If these viruses spread more widely, they will represent another antigenic shift for our swine population, and could pose a threat to the world's human population. Research on these novel viruses may offer important clues to the genetic basis for interspecies transmission of influenza viruses.

            Descriptors:  influenza virology, influenza A virus, porcine physiology, Canada epidemiology, fowl plague transmission, influenza A virus avian,  influenza A virus, porcine classification, influenza A virus, porcine genetics,  influenza A virus, porcine immunology, North America epidemiology, species specificity, swine, United States, variation genetics.

Olsen, C.W., S. Carey, L. Hinshaw, and A.I. Karasin (2000). Virologic and serologic surveillance for human, swine and avian influenza virus infections among pigs in the north-central United States. Archives of Virology 145(7): 1399-419.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Influenza virus infection in pigs is both an animal health problem and a public health concern. As such, surveillance and characterization of influenza viruses in swine is important to the veterinary community and should be a part of human pandemic preparedness planning. Studies in 1976/1977 and 1988/1989 demonstrated that pigs in the U.S. were commonly infected with classical swine H1N1 viruses, whereas human H3 and avian influenza virus infections were very rare. In contrast, human H3 and avian H1 viruses have been isolated frequently from pigs in Europe and Asia over the last two decades. From September 1997 through August 1998, we isolated 26 influenza viruses from pigs in the north central United States at the point of slaughter. All 26 isolates were H1N1 viruses, and phylogenetic analyses of the hemagglutinin and nucleoprotein genes from 11 representative viruses demonstrated that these were classical swine H1 viruses. However, monoclonal antibody analyses revealed antigenic heterogeneity among the HA proteins of the 26 viruses. Serologically, 27.7% of 2,375 pigs tested had hemagglutination-inhibiting antibodies against classical swine H1 influenza virus. Of particular significance, however, the rates of seropositivity to avian H1 (7.6%) and human H3 (8.0%) viruses were substantially higher than in previous studies.

            Descriptors:  influenza veterinary, influenza virology, influenza A virus avian isolation and purification, influenza A virus human isolation and purification, influenza A virus, porcine isolation and purification, swine diseases virology, amino acid sequence, influenza epidemiology, molecular sequence data,  seroepidemiologic studies, swine, swine diseases epidemiology, United States epidemiology.

Osterhaus, A.D., R.A. Fouchier, and T. Kuiken (2004). The aetiology of SARS: Koch's postulates fulfilled. Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 359(1447): 1081-2.  ISSN: 0962-8436.

            NAL Call Number:  501 L84Pb

            Abstract:  Proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca fascicularis). SARS-CoV-infected macaques developed a disease comparable to SARS in humans; the virus was re-isolated from these animals and they developed SARS-CoV-specific antibodies. This completed the fulfilment of Koch's postulates, as modified by Rivers for viral diseases, for SARS-CoV as the aetiological agent of SARS. Besides the macaque model, a ferret and a cat model for SARS-CoV were also developed. These animal models allow comparative pathogenesis studies for SARS-CoV infections and testing of different intervention strategies. The first of these studies has shown that pegylated interferon-alpha, a drug approved for human use, limits SARS-CoV replication and lung damage in experimentally infected macaques. Finally, we argue that, given the worldwide nature of the socio-economic changes that have predisposed for the emergence of SARS and avian influenza in Southeast Asia, such changes herald the beginning of a global trend for which we are ill prepared.

            Descriptors:  disease models, animal, ferrets, Macaca fascicularis, SARS virus, severe acute respiratory syndrome etiology, zoonoses transmission, cats, severe acute respiratory syndrome physiopathology, severe acute respiratory syndrome transmission.

Otsuki, K., K. Yamazaki, Y. Kawaoka, and M. Tsubokura (1987). Infectivity for mice of avian influenza A viruses of H7N7, H5N3 and H2N2 subtypes isolated from migratory waterfowls in San-in District, Western Japan. Nippon Juigaku Zasshi Japanese Journal of Veterinary Science 49(1): 199-201.  ISSN: 0021-5295.

            NAL Call Number:  41.8 J27

            Descriptors:  birds microbiology, influenza A virus avian pathogenicity, mice microbiology, influenza A virus avian isolation and purification, Japan.

Oxford, J.S., R. Lambkin, A. Sefton, R. Daniels, A. Elliot, R. Brown, and D. Gill (2005). A hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern France during the Great War provided the conditions for the emergence of the "Spanish" influenza pandemic of 1918-1919. Vaccine  23(7): 940-5.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  The Great Influenza Pandemic of 1918-1919 was a cataclysmic outbreak of infection wherein over 50 million people died worldwide within 18 months. The question of the origin is important because most influenza surveillance at present is focussed on S.E. Asia. Two later pandemic viruses in 1957 and 1968 arose in this region. However we present evidence that early outbreaks of a new disease with rapid onset and spreadability, high mortality in young soldiers in the British base camp at Etaples in Northern France in the winter of 1917 is, at least to date, the most likely focus of origin of the pandemic. Pathologists working at Etaples and Aldershot barracks later agreed that these early outbreaks in army camps were the same disease as the infection wave of influenza in 1918. The Etaples camp had the necessary mixture of factors for emergence of pandemic influenza including overcrowding (with 100,000 soldiers daily changing), live pigs, and nearby live geese, duck and chicken markets, horses and an additional factor 24 gases (some of them mutagenic) used in large 100 ton quantities to contaminate soldiers and the landscape. The final trigger for the ensuing pandemic was the return of millions of soldiers to their homelands around the entire world in the autumn of 1918.

            Descriptors:  communicable diseases, emerging history, disease outbreaks, influenza history, military personnel history, world war I, ducks, France, geese, history, 20th century, horses, influenza A virus, avian pathogenicity, swine.

Ozaki, H., E.A. Govorkova, C. Li, X. Xiong, R.G. Webster, and R.J. Webby (2004). Generation of high-yielding influenza A viruses in African green monkey kidney (Vero) cells by reverse genetics. Journal of Virology 78(4): 1851-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. Recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategies to produce influenza vaccine. Although cell-based systems are being developed, barriers remain that need to be overcome if the potential of these systems is to be fully realized. These barriers include, but are not limited to, potentially poor reproducibility of viral rescue with reverse genetics systems and poor growth kinetics and yields. In this study we present a modified A/Puerto Rico/8/34 (PR8) influenza virus master strain that has improved viral rescue and growth properties in the African green monkey kidney cell line, Vero. The improved properties were mediated by the substitution of the PR8 NS gene for that of a Vero-adapted reassortant virus. The Vero growth kinetics of viruses with H1N1, H3N2, H6N1, and H9N2 hemagglutinin and neuraminidase combinations rescued on the new master strain were significantly enhanced in comparison to those of viruses with the same combinations rescued on the standard PR8 master strain. These improvements pave the way for the reproducible generation of high-yielding human and animal influenza vaccines by reverse genetics methods. Such a means of production has particular relevance to epidemic and pandemic use.

            Descriptors:  influenza A virus avian growth and development, influenza A virus human growth and development, influenza vaccine, reassortant viruses growth and development, vero cells virology, Cercopithecus aethiops, influenza A virus avian genetics, influenza A virus human genetics, reassortant viruses genetics, viral nonstructural proteins genetics, virus cultivation, virus replication.

Papparella, V., A. Fioretti, L.F. Menna, JM Bruce (ed.), and S. M. (1987). On the danger of certain avian respiratory diseases to human health. In: Environmental aspects of respiratory disease in intensive pig and poultry houses, including the implications for human health. Report Eur 10820 EN, Aberdeen, UK, Commission of he European Communities: Luxembourg, p. 127-132.

            Descriptors: zoonoses, public health,  humans, Newcastle disease virus, avian influenza virus.

Park, C.H., K. Matsuda, Y. Sunden, A. Ninomiya, A. Takada, H. Ito, T. Kimura, K. Ochiai, H. Kida, and T. Umemura (2003). Persistence of viral RNA segments in the central nervous system of mice after recovery from acute influenza A virus infection. Veterinary Microbiology 97(3-4): 259-68.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  One-hundred thirty-seven BALB/c mice were intranasally inoculated with neurotropic avian influenza A virus (H5N3). Thirty-nine of these mice died within 16 days post-inoculation (PID) and 98 of the mice recovered from the infection. To investigate whether viral antigens and genomes persist in the central nervous system (CNS) of recovered mice, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods were performed. Histopathologically, mild interstitial pneumonia and non-suppurative encephalomyelitis restricted to the basal part of the frontal lobe of the cerebrum, brain stem and thoracic spinal cord were observed in BALB/c mice until 40 PID. Small amounts of viral antigens were detected in the brain and spinal cord and some viral RNA segments (NA, NP, M, PA, HA, NS, PB1) were intermittently detected in the CNS until 48 PID. Immunosuppression of these mice by dexamethazone (DEX) treatment did not increase the frequency of detection of the lesions, viral antigens or genomes. These findings suggest that viral genomes of neurovirulent influenza virus persist with restricted transcriptive activity in the CNS of the mice even after clinical recovery from the infection.

            Descriptors:  central nervous system virology, fowl plague virology, influenza A virus avian isolation and purification, RNA viral analysis, brain pathology, brain virology, central nervous system pathology, disease models, animal, fowl plague mortality, fowl plague pathology, immunohistochemistry veterinary, influenza A virus avian genetics, mice, mice inbred BALB c, random allocation, reverse transcriptase polymerase chain reaction veterinary, specific pathogen free organisms.

Parry, J. (2004). Death toll mounts in avian flu outbreak. BMJ Clinical Research 328(7434): 243.  ISSN: 1468-5833.

            Descriptors:  disease outbreaks, fowl plague virology, influenza mortality, Asia, southeastern epidemiology, birds, influenza A virus avian, influenza A virus human.

Parry, J. (2004). WHO investigates possible human to human transmission of avian flu. BMJ Clinical Research 328(7435): 308.  ISSN: 1468-5833.

            Descriptors:  influenza, avian transmission, zoonoses transmission, influenza, avian epidemiology, poultry, Vietnam epidemiology.

Parry, J. (2004). WHO warns that avian flu could still be in the environment. BMJ Clinical Research 328(7437): 426.  ISSN: 1468-5833.

            Descriptors:  influenza, avian epidemiology, birds, Carnivora, cat diseases epidemiology, cats, poultry, world health, World Health Organization.

Pasick, J., K. Handel, J. Robinson, J. Copps, D. Ridd, K. Hills, H. Kehler, C. Cottam Birt, J. Neufeld, Y. Berhane, and S. Czub (2005). Intersegmental recombination between the haemagglutinin and matrix genes was responsible for the emergence of a highly pathogenic H7N3 avian influenza virus in British Columbia. Journal of General Virology 86(Pt. 3): 727-31.  ISSN: 0022-1317.

            NAL Call Number:  QR360.A1J6

            Abstract:  In February 2004 a highly pathogenic avian influenza (HPAI) outbreak erupted in British Columbia. Investigations indicated that the responsible HPAI H7N3 virus emerged suddenly from a low pathogenic precursor. Analysis of the haemagglutinin (HA) genes of the low and high pathogenic viruses isolated from the index farm revealed the only difference to be a 21 nt insert at the HA cleavage site of the highly pathogenic avian influenza virus. It was deduced that this insert most probably arose as a result of non-homologous recombination between the HA and matrix genes of the same virus. Over the course of the outbreak, a total of 37 isolates with, and 3 isolates without inserts were characterized. The events described here appear very similar to those which occurred in Chile in 2002 where the virulence shift of another H7N3 virus was attributed to non-homologous recombination between the HA and nucleoprotein genes.

            Descriptors:  veterinary disease outbreaks, hemagglutinins viral genetics, avian influenza A virus genetics, avian influenza epidemiology, genetic recombination, viral matrix proteins genetics, British Columbia.

Peiris, J.S., Y. Guan, D. Markwell, P. Ghose, R.G. Webster, and K.F. Shortridge (2001). Cocirculation of avian H9N2 and contemporary "human" H3N2 influenza A viruses in pigs in southeastern China: potential for genetic reassortment? Journal of Virology 75(20): 9679-86.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Pigs are permissive to both human and avian influenza viruses and have been proposed to be an intermediate host for the genesis of pandemic influenza viruses through reassortment or adaptation of avian viruses. Prospective virological surveillance carried out between March 1998 and June 2000 in Hong Kong, Special Administrative Region, People's Republic of China, on pigs imported from southeastern China, provides the first evidence of interspecies transmission of avian H9N2 viruses to pigs and documents their cocirculation with contemporary human H3N2 (A/Sydney/5/97-like, Sydney97-like) viruses. All gene segments of the porcine H9N2 viruses were closely related to viruses similar to chicken/Beijing/1/94 (H9N2), duck/Hong Kong/Y280/97 (H9N2), and the descendants of the latter virus lineage. Phylogenetic analysis suggested that repeated interspecies transmission events had occurred from the avian host to pigs. The Sydney97-like (H3N2) viruses isolated from pigs were related closely to contemporary human H3N2 viruses in all gene segments and had not undergone genetic reassortment. Cocirculation of avian H9N2 and human H3N2 viruses in pigs provides an opportunity for genetic reassortment leading to the emergence of viruses with pandemic potential.

            Descriptors:  influenza A virus avian isolation and purification, influenza A virus human isolation and purification, swine virology, antibodies, viral blood, carrier state epidemiology, carrier state veterinary, cell line, China epidemiology, influenza epidemiology, influenza veterinary, influenza A virus avian classification, influenza A virus avian genetics, influenza A virus human classification, influenza A virus human genetics, molecular sequence data, phylogeny, sequence homology, nucleic acid, seroepidemiologic studies.

Perdue, M.L. (2003). Molecular diagnostics in an insecure world. Avian Diseases 47(Special Issue): 1063-1068.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  As of October 2001, the potential for use of infectious agents, such as anthrax, as weapons has been firmly established. It has been suggested that attacks on a nations' agriculture might be a preferred form of terrorism or economic disruption that would not have the attendant stigma of infecting and causing disease in humans. Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents, generally following foot and mouth disease virus and Newcastle disease virus at or near the top of the list. Rapid detection techniques for bioweapon agents are a critical need for the first-responder community, on a par with vaccine and antiviral development in preventing spread of disease. There are several current approaches for rapid, early responder detection of biological agents including influenza A viruses. There are also several proposed novel approaches in development. The most promising existing approach is real-time fluorescent PCR analysis in a portable format using exquisitely sensitive and specific primers and probes. The potential for reliable and rapid early-responder detection approaches are described, as well as the most promising platforms for using real-time PCR for avian influenza, as well as other potential bioweapon agents.

            Descriptors:  immune system, infection, molecular genetics, molecular diagnostics clinical techniques, diagnostic techniques, real time fluorescent polymerase chain reaction, real time fluorescent PCR, genetic techniques, laboratory techniques, agricultural bioweapon agents, bioterrorism, economic disruption, rapid disease detection.

Perez, D.R., R.J. Webby, E. Hoffmann, and R.G. Webster (2003). Land-based birds as potential disseminators of avian/mammalian reassortant influenza A viruses. Avian Diseases 47(Special Issue): 1114-1117.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Chickens, quail, and other land-based birds are extensively farmed around the world. They have been recently implicated in zoonotic outbreaks of avian influenza in Hong Kong. The possibility that land-based birds could act as mixing vessels or disseminators of avian/mammalian reassortant influenza A viruses with pandemic potential has not been evaluated. In this report, we investigated whether chickens and Japanese quail are susceptible to a mammalian influenza virus (A/swine/Texas/4199-2/98 (H3N2)). This virus did not grow in chickens and replicated to low levels in Japanese quail but did not transmit. Replacing the H3 gene of this virus for one of the avian H9 viruses resulted in transmission of the avian/swine reassortant virus among quail but not among chickens. Our findings demonstrated that Japanese quail could provide an environment in which viruses like the A/swine/Texas/4199-2/98 (H3N2) virus could further reassort and generate influenza viruses with pandemic potential.

            Descriptors:  epidemiology, infection, avian influenza, infectious disease, respiratory system disease, viral disease, pandemic potentials, zoonotic influenza outbreaks.

Perkins, L.E.L. and D.E. Swayne (2003). Comparative susceptibility of selected avian and mammalian species to a Hong Kong-Origin H5N1 high-pathogenicity avian influenza virus. Avian Diseases 47(Special Issue): 956-967.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Seventeen avian species and two mammalian species were intranasally inoculated with the zoonotic A/chicken/Hong Kong/220/97 (chicken/HK) (H5N1) avian influenza (AI) virus in order to ascertain a relative range of susceptible hosts and the pathobiology of the resultant disease. A direct association was demonstrated between viral replication and the severity of disease, with four general gradations being observed among these species. These gradations included the following: 1) widespread dissemination with rapid and high mortality, 2) neurological disease relative to viral neurotropism, 3) asymptomatic infection or only mild transient depression associated with minor viral replication, and 4) absence of disease relative to minimal to no viral replication. This investigation not only demonstrates that the chicken/HK virus could infect multiple avian species, but also that the virulence of the chicken/HK virus varied significantly among avian species, including those species that are members of the same order.

            Descriptors:  epidemiology, infection, avian influenza, infectious disease, respiratory system disease, viral disease, inoculation, clinical techniques, therapeutic and prophylactic techniques, disease severity, disease susceptibility, host susceptibility, pathobiology, viral neurotropism, viral replication.

Perkins, L.E.L. and D.E. Swayne (2002). Pathogenicity of a Hong Kong-origin H5N1 highly pathogenic avian influenza virus for emus, geese, ducks, and pigeons. Avian Diseases 46(1): 53-63.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The H5N1 type A influenza viruses that emerged in Hong Kong in 1997 are a unique lineage of type A influenza viruses with the capacity to transmit directly from chickens to humans and produce significant disease and mortality in-both of these hosts. The objective of this study was to ascertain the susceptibility of emus (Dramaius novaehollandiae), domestic geese (Anser anser domesticus), domestic ducks (Anas platyrhynchos), and pigeons (Columba livia) to intranasal (i.n.) inoculation with the A/chicken/Hong Kong/220/97 (H5N1) highly pathogenic avian influenza virus. No mortality occurred within 10 days postinoculation (DPI) in the four species investigated, and clinical disease, evident as neurologic dysfunction, was observed exclusively in emus and geese. Grossly, pancreatic mottling and splenomegaly were identified in these two species. In addition, the geese had cerebral malacia and thymic and bursal atrophy. Histologically, both the emus and geese developed pancreatitis, meningoencephalitis, and mild myocarditis. Influenza viral antigen was demonstrated in areas with histologic lesions up to 10 DPI in the geese. Virus was reisolated from oropharyngeal and cloacal swabs and from the lung, brain, and kidney of the emus and geese. Moderate splenomegaly was observed grossly in the ducks. Viral infection of the ducks was pneumotropic, as evidenced by mild inflammatory lesions in the respiratory tract and virus reisolation from oropharyngeal swabs and from a lung. Pigeons were resistant to HK/220 infection, lacking gross and histologic lesions, viral antigen, and reisolation of virus. These results imply that emus and geese are susceptible to i.n. inoculation with the HK/220 virus, whereas ducks and pigeons are more resistant. These latter two species probably played a minimal epidemiologic role in the perpetuation of the H5N1 Hong Kong-origin influenza viruses.

            Descriptors:  infection, veterinary medicine, H5N1 avian influenza virus infection, etiology, mortality, viral disease, bursal atrophy, joint disease, cerebral malacia, nervous system disease, meningoencephalitis, nervous system disease, myocarditis, heart disease, neurologic dysfunction, nervous system disease, pancreatic mottling, digestive system disease, endocrine disease, pancreas, pancreatitis, digestive system disease, respiratory tract inflammation, respiratory system disease, splenomegaly, blood and lymphatic disease, thymic atrophy, endocrine disease, thymus.

Permin, A. (2004). Avian influenza is spreading. Now avian influenza is also in pigs [Aviaer influenza breder sig nu ogsa aviaer influenza hos svin]. Dansk Veterinaertidsskrift 87(19): 10-11.  ISSN: 0106-6854.

            NAL Call Number:  41.9 D23

            Descriptors:  avian influenza virus, pigs, poultry.

Permin, A. (2003). A veterinarian dies from avian influenza virus infection. Dansk Veterinaertidsskrift 86(13): 13-15.  ISSN: 0106-6854.

            NAL Call Number:  41.9 D23

            Descriptors:  avian influenza virus, zoonoses, human death, Denmark, Holland.

Pilet, C. (1980). Proceedings of an International Symposium, held on September 13 and 14, 1979 at the Ecole Nationale Veterinaire d'Alfort, France. Comparative Immunology, Microbiology and Infectious Diseases. Special Issue on Animal and Human Influenzas 3(1/2): xvi + 246.  ISSN: 0147-9571.

            NAL Call Number:  QR180.C62

            Descriptors:  influenza virus, humans, zoonoses, equine, porcine, avian, symposium.

Pilet, C., G. Dauphin, and S. Zientara (2004). Actualites en pathologie comparee: sur quelques maladies animales menacantes pour l'homme. [Advances in comparative pathology: some zoonoses threatening man]. Bulletin De L'Academie Nationale De Medecine 188(5): 823-36.  ISSN: 0001-4079.

            Abstract:  The last major human epidemics of infectious diseases have arisen from animals. Some of them are especially threatening. The authors call attention to the danger of spread of avian influenza, either directly or indirectly through genetic rearrangements. They underline the role of animals in the epidemiology of SARS, West Nile virus, hepatitis E, NIPA and Hendra virus, ehrlichiosis and Lyme disease. The authors recommend health surveillance not only in humans but also in animals; the teaching of zoonoses, and research on animal diseases transmissible to humans.

            Descriptors:  virus diseases transmission, zoonoses.

Podcherniaeva, R.I.A., V.K. Blinova, M.V. Ronina, E.I. Sklianskaia, and N.V. Kaverin (1980). Antigennye rekombinanty virusov grippa cheloveka s virusami, vydelennymi ot dikikh ptits. [Antigenic recombinants of human influenza viruses with viruses isolated from wild birds]. Voprosy Virusologii (4): 419-24.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  Antigenic recombinants obtained by crossing of different human and animal influenza viruses were studied for some genetic markers and specific proteins in the resulting recombinants were analyses. In a number of cases the origin of inner virion proteins (NP and M) from one or the other parent and nonstructural NS proteins was established.

            Descriptors:  antigens, viral genetics, birds microbiology, influenza A virus avian genetics, influenza A virus human genetics, recombination, genetic, antigens, viral analysis, genetic markers, species specificity, viral proteins genetics.

Podchernyaeva, R.J., R.G. Webster, V.V. Skovorodka, A.I. Klimov, and V.M. Zhdanov (1989). Molecular and biological properties of a variant of avian influenza A/Seal/Massachusetts/1/80 (H7N7) virus that is pathogenic for mice. Acta Virologica 33(1): 38-42.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  A/Seal/Mass/80 influenza virus has been shown to be closely related antigenically and genetically to avian influenza H7N7 viruses, however, the virus does not replicate efficiently in avian species but does replicate in most mammals, except mice (Hinshaw et al., Infect. Immun., 34, 351-361, 1981). In order to develop a model defining the molecular changes that occur during acquisition of virulence, the A/Seal/Mass/80 virus was adapted to growth in mouse lungs. The adaptation was accompanied by changes in a number of properties of the haemagglutinin as well as by changes in other genes of the virus as determined by RNA: RNA hybridization.

            Descriptors:  influenza A virus pathogenicity, genes viral, hemagglutinins viral, influenza A virus genetics, lethal dose 50, lung microbiology, mice, neutralization tests, nucleic acid hybridization, RNA viral analysis, serial passage, variation genetics, virulence.

Poli, G. and L. Bonizzi (2004). Avian influenza: not a danger [Influenza aviare: nessun pericolo]. Informatore Agrario 60(11): 33-34.  ISSN: 0020-0689.

            NAL Call Number:  281.8 In32

            Descriptors:  avian influenza virus, disease prevention, disease transmission, hygiene, occupational transmission, poultry, poultry farming.

Pollack, C.V.J., C.W. Kam, and Y.K. Mak (1998). Update: isolation of avian influenza A(H5N1) viruses from human beings--Hong Kong, 1997-1998. Annals of Emergency Medicine 31(5): 647-9.  ISSN: 0196-0644.

            Descriptors:  disease outbreaks, influenza transmission, influenza virology, influenza A virus human,  poultry diseases transmission, poultry diseases virology, adolescent, adult, case control studies, chickens, child, child, preschool, ducks, Hong Kong epidemiology, infant, influenza epidemiology, influenza veterinary, middle aged, neutralization tests, population surveillance, poultry diseases epidemiology.

Pospisil, Z., P. Lany, J. Buchta, D. Zendulkova, P. Cihal, and B. Tumova (2001). Swine influenza surveillance and the impact of human influenza epidemics on pig herds in the Czech Republic. Acta Veterinaria (Czech Republic) 70(3): 327-332.  ISSN: 0001-7213.

            NAL Call Number:  SF604.B7

            Abstract:  Epizootiological and virological surveys carried out between 1995 and mid-2000 corroborated the findings from the end of the 1970s that swine influenza did not cause any serious problems in pig herds in the Czech Republic. In the present study, no antibodies against either swine influenza virus, types A (H1N1) and A (H3N2), or avian influenza virus, A (H1N1), were demonstrated and no influenza virus was isolated. In contrast, antibodies against the human influenza virus isolated during the 1995 epidemic were found. The dynamics of antibody formation indicated that the human virus gradually disappeared from the pig population. It is possible that the human virus was introduced to the pig herds by infected animal attendants, in whom antibodies against this virus were also found. During the second human influenza epidemic in 1998/99, however, pigs remained free from antibody response to influenza virus.

            Descriptors:  swine, swine influenza virus, serotypes, antibodies, zoonoses, disease transmission, disease surveillance, Czech Republic, biological differences, domestic animals, Eastern Europe, epidemiology, Europe, immunological factors, influenza virus, livestock, orthomyxoviridae, pathogenesis, Suidae, useful animals, viruses.

Potter, P. (2004). "One medicine" for animal and human health. Emerging Infectious Diseases 10(12): 2269-2270.  ISSN: 1080-6040.

            NAL Call Number:  RA648.5.E46

            Descriptors:  AIDS, acquired immunodeficiency syndrome, Ebola virus disease, SARS, severe acute respiratory syndrome, West Nile fever, avian influenza, bovine spongiform encephalopathy, prion disease, Edward Hicks artist, zoonosis, biography, history, epidemiology.

Profeta, M.L. and G. Palladino (1986). Serological evidence of human infections with avian influenza viruses. Brief report. Archives of Virology 90(3-4): 355-60.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Two hundred ninety-four subjects from Milan were tested for serum hemagglutination-inhibiting (HI) and neuraminidase-inhibiting (NI) antibodies to five avian influenza viruses. No HI antibodies were found in all the serum samples. On the contrary, NI antibodies to each strain were detected depending on the year of birth of the subjects.

            Descriptors:  influenza immunology, influenza A virus avian immunology, hemagglutination inhibition tests, hemagglutinins viral immunology, influenza microbiology, influenza A virus avian pathogenicity, neuraminidase antagonists and inhibitors, neuraminidase immunology.

Prokudina, E.N., N.P. Semenova, V.M. Chumakov, E.I. Burtseva, and A.N. Slepushkin (2003).  Differences in oligomerization of the nucleocapsid protein of epidemic human influenza A(H1N1), A(H3N2) and B viruses. Voprosy Virusologii 48(3): 27-31.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A comparative analysis of involving the nucleocapsid protein (NP) into shaping-up of SDS-resistant oligomers was carried out presently in circulating epidemic strains of human influenza, viruses A and B. The study results of viral isolates obtained from clinical samples and recent standard strains revealed that the involvement of NP in the SDS-resistant oligomers, which are different in various subtypes of influenza A viruses. According to this sign, the human viruses A(9H3N2) are close to the avian ones, in which, as proved by us previously, virtually the entire NP transforms itself into the oligomers resistant to SDS. About 10-20% of NP are involved in shaping-up the virus influenza A(H1N1) of SDS-resistant oligomers. No SDS-resistant NP-oligomers were detected in influenza of type B. It is suggested that the prevalence of human viruses A(H3N2) in NP-oligomers are the peculiarities of NP structure and of the presence of the PB1 protein from avian influenza virus.

            Descriptors:  computer applications, infection, molecular genetics, SDS page, SDS polyacrylamide gel electrophoresis, electrophoretic techniques, laboratory techniques, comparative analysis laboratory techniques.

Prokudina, E.N., N.P. Semenova, I.A. Rudneva, V.M. Chumakov, and S.S. Yamnikova (2001). Avian and human influenza a virus strains possess different intracellular nucleoprotein oligomerization efficiency. Acta Virologica 45(4): 201-7.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  We have previously shown (Prokudina-Kantorovich EN and Semenova NP, Virology 223, 51-56, 1996) that the nucleoprotein (NP) of influenza A virus forms in infected cells oligomers which in the presence of SDS and 2-mercaptoethanol (ME) as reducing agent are stable at room temperature (RT) and dissociate at 100 degrees C. Here we report that the efficiency of intracellular NP oligomerization depends on the host origin of influenza A virus strain. Thus, in the cells infected with avian influenza A virus strains the viral NP was almost completely oligomerized and only traces of monomeric NP were detected by polyacrylamide gel electrophoresis (PAGE) in unboiled samples. However, in the cells infected with human influenza A virus strains, besides oligomeric NP also a significant amount of non-oligomerized monomeric NP was detected in unboiled samples. In purified virions of avian and human strains the same difference in NP monomers/oligomers ratio was detected as in the infected cells. A reassortant having all internal protein genes from a human strain and the glycoprotein genes from an avian strain revealed the same intracellular pattern of NP monomers/oligomers ratio as its parental human virus. These findings suggest that the type of NP oligomerization is controlled by the NP gene. The possible connection between the accumulation of protease-sensitive monomeric NP in cells infected with a human influenza strain and the parallel accumulation of cleaved NP in these cells is discussed.

            Descriptors:  influenza A virus metabolism, nucleoproteins metabolism, viral core proteins metabolism, biopolymers analysis, cell line, dogs, influenza A virus avian metabolism, influenza A virus human metabolism, influenza A virus genetics, nucleoproteins analysis, nucleoproteins genetics, reassortant viruses metabolism, species specificity, viral core proteins analysis, viral core proteins genetics.

Pysina, T.V. and A.S. Gorbunova (1970). Sootnosheniia mezhdu patogennost'iu virusov grippa ptits dlia laboratornykh zhivotnykh i infitsirovaniem avifauny. [Relation between the pathogenicity of avian influenza viruses for laboratory animals and infection of avifauna]. Voprosy Virusologii 15(3): 298-301.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Descriptors:  bird diseases microbiology, orthomyxoviridae pathogenicity, bird diseases epidemiology, chickens, Czechoslovakia, ducks, England,  influenza epidemiology, influenza microbiology, mice, Scotland, Siberia, South Africa, tissue culture, virus cultivation.

Quirk, M. (2004). USA to manufacture two million doses of pandemic flu vaccine. Lancet Infectious Diseases 4(11): 654.  ISSN: 1473-3099.

            Descriptors:  influenza prevention and control, influenza A virus, avian immunology, influenza vaccines supply and distribution, drug industry, United States, vaccination.

Quirk, M. (2004). Zoo tigers succumb to avian influenza. Lancet Infectious Diseases 4(12): 716.  ISSN: 1473-3099.

            Descriptors:  disease outbreaks veterinary, food contamination, influenza, avian epidemiology, tigers, animal feed standards, animal feed virology, newborn animals, zoo animals, chickens, disease susceptibility veterinary, avian influenza mortality, avian influenza transmission, Thailand epidemiology.

Raleigh, P.J. (2004). Avian influenza. Irish Veterinary Journal 57(3): 154-156.  ISSN: 0368-0762.

            NAL Call Number:  41.8 Ir4

            Descriptors:  avian influenza virus, diagnosis, disease control, disease prevention, disease transmission, fowl diseases, lesions, poultry, viral replication, zoonoses, fowl, reviews.

Rassool, G.H. (2004). Unprecedented spread of avian influenza requires broad collaboration. Journal of Advanced Nursing 46(5): 567.  ISSN: 0309-2402.

            Descriptors:  disease outbreaks prevention and control, influenza A virus, avian influenza, avian influenza prevention and control, avian influenza transmission, international cooperation, zoonoses transmission.

Ready, T. (2004). Race for pandemic flu vaccine rife with hurdles. Nature Medicine 10(3): 214.  ISSN: 1078-8956.

            Descriptors:  influenza prevention and control, influenza A virus, avian immunology, influenza vaccines, chickens, clinical trials, influenza virology.

Reid, A.H., J.K. Taubenberger, and T.G. Fanning (2004). Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus. Nature Reviews Microbiology 2(11): 909-14.  ISSN: 1740-1526.

            Abstract:  Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.

            Descriptors:  influenza history, influenza virology, influenza A virus, human genetics, variation genetics, viral proteins genetics, disease outbreaks, hemagglutinin glycoproteins, influenza virus genetics, history, 20th century, influenza epidemiology, mutation, neuraminidase genetics, nucleoproteins genetics, reassortant viruses genetics, viral matrix proteins genetics, viral nonstructural proteins genetics.

Reina, J. (2002). Factores de virulencia y patogenicidad en las cepas gripales (virus influenza tipo A) aviares y humanas. [Factors affecting the virulence and pathogenicity of avian and human viral strains (influenza virus type A)]. Enfermedades Infecciosas y Microbiologia Clinica 20(7): 346-53.  ISSN: 0213-005X.

            Abstract:  Most studies performed in avian viral strains seem to indicate that virulence is a polygenic phenomenon. However, hemagglutinin and neuraminidase and the genes codifying these substances (genes 4 and 6) play an essential role in viral pathogenesis. Avian strains can be classified as avirulent or virulent according to the ability of hemagglutinin to be activated by endoproteases of the respiratory tract only or by proteases from other tissues. This ability is based on the progressive development of mutations that lead to the substitution of the normal amino acids at the point of hemagglutinin hydrolysis by the other basic amino acids that determine the amplification of the spectrum of hydrolysis and activation. Neuraminidase participates in the acquisition of virulence through its capacity to bind to plasminogen and by increasing the concentration of activating proteases. Adaptation to the host, through recognition of the cell receptor, is another factor determining the virulence and interspecies transmission of avian strains. From an epidemiological point of view, viral strains should be subtyped and the activating capacity of hemagglutinin should be determined to identify their degree of virulence.

            Descriptors:  influenza A virus avian pathogenicity, influenza A virus human pathogenicity, hemagglutinins, neuraminidase, peptide hydrolases, virulence.

Reina, J. (2004). Gripe aviar. Una amenaza constante para el ser humano. [Avian influenza. A continual threat to human beings]. Medicina Clinica 122(9): 339-41.  ISSN: 0025-7753.

            NAL Call Number:  R21.M43

            Descriptors:  avian influenza, humans, continual threat, birds, pigs.

Reinhardt, U. and C. Scholtissek (1988). Comparison of the nucleoprotein genes of a chicken and a mink influenza A H 10 virus. Archives of Virology 103(1-2): 139-45.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The base sequences of the coding region of the nucleoprotein (NP) genes of two H 10 influenza A viruses, one avian (virus N) and one mink virus, have been determined by primer extension. When the NP genes and the NP sequences derived from the only open reading frame of the two H 10 viruses were compared with those of other human and avian influenza A viruses, it turned out that the mink virus NP was highly related to that of other avian strains, but differed from that of the human strains. Comparison of the NP genes of the mink and avian strains of European origin suggests a direct lineage between them. Since the NP plays a major role in species specificity, it is assumed that an avian influenza virus has directly invaded the mink population.

            Descriptors:  base sequence, influenza A virus avian genetics, influenza A virus genetics, nucleoproteins genetics, RNA, viral, sequence homology, nucleic acid, viral proteins genetics, amino acid sequence, chickens microbiology, mink microbiology, molecular sequence data.

Renegar, K.B. (1992). Influenza virus infections and immunity: a review of human and animal models. Laboratory Animal Science 42(3): 222-32.  ISSN: 0023-6764.

            NAL Call Number:  410.9 P94

            Abstract:  Studies of the pathogenesis of influenza infection have involved the extensive use of animal models. The development of the current concepts of immunity to influenza and of the contribution the secretory immune system makes toward the protection of mucosal surfaces against influenza infection would have been impossible without this use of animals. The pathology and clinical signs of influenza infection in both natural and experimental hosts, the advantages and disadvantages of the most common experimental influenza infection models, and the contribution of animal models to the understanding of local and systemic immunity to influenza infection are discussed.

            Descriptors:  influenza immunology, influenza veterinary, antibody formation, disease models, animal, ferrets, fowl plague immunology, hamsters, haplorhini, horse diseases immunology, horses, influenza A virus avian, influenza A virus human, influenza A virus, porcine, influenza A virus, influenza vaccine administration and dosage, mice.

Rezza, G. (2004). Avian influenza: a human pandemic threat?  Journal of Epidemiology and Community Health 58(10): 807-8.  ISSN: 0143-005X.

            Descriptors:  disease outbreaks, influenza epidemiology, influenza, avian transmission, zoonoses epidemiology, communicable diseases, emerging epidemiology, communicable diseases, emerging prevention and control, influenza prevention and control.

Riberdy, J.M., K.J. Flynn, J. Stech, R.G. Webster, J.D. Altman, and P.C. Doherty (1999). Protection against a lethal avian influenza A virus in a mammalian system. Journal of Virology 73(2): 1453-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy would be to vaccinate with a less virulent, laboratory-adapted H5N1 strain isolated previously from birds. Little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza A viruses using contemporary immunology techniques. Such experiments with the H5N1 viruses are limited by the potential risk to humans. An extremely virulent H3N8 avian influenza A virus has been used to infect both immunoglobulin-expressing (Ig+/+) and Ig-/- mice primed previously with a laboratory-adapted H3N2 virus. The cross-reactive antibody response was very protective, while the recall of CD8(+) T-cell memory in the Ig-/- mice provided some small measure of resistance to a low-dose H3N8 challenge. The H3N8 virus also replicated in the respiratory tracts of the H3N2-primed Ig+/+ mice, generating secondary CD8(+) and CD4(+) T-cell responses that may contribute to recovery. The results indicate that the various components of immune memory operate together to provide optimal protection, and they support the idea that related viruses of nonhuman origin can be used as vaccines.

            Descriptors:  influenza prevention and control, influenza A virus avian immunology, influenza vaccine immunology, base sequence, birds, CD4 positive T lymphocytes immunology, CD8 positive T lymphocytes immunology, DNA, viral, disease models, animal, immunoglobulins immunology, influenza immunology, mice, mice inbred BALB c, mice, inbred c57bl, molecular sequence data.

Rimmelzwaan, G.F., E.C.J. Claas, G. van Amerongen, J.C. de Jong, and A.D.M.E. Osterhaus (1999). ISCOM vaccine induced protection against a lethal challenge with a human H5N1 influenza virus. Vaccine 17(11-12): 1355-1358.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  Recently avian influenza A viruses of the H5N1 subtype were shown to infect humans in the Hong Kong area, resulting in the death of six people. Although these viruses did not efficiently spread amongst humans, these events illustrated that influenza viruses of subtypes not previously detected in humans could be at the basis of a new pandemic. In the light of this pandemic threat we evaluated and compared the efficacy of a classical non-adjuvanted subunit vaccine and a vaccine based on immune stimulating complexes (ISCOM) prepared with the membrane glycoproteins of the human influenza virus A/Hong Kong/156/97 (H5N1) to protect roosters against a lethal challenge with this virus. The ISCOM vaccine induced protective immunity against the challenge infection whereas the non-adjuvanted subunit vaccine proved to be poorly immunogenic and failed to induce protection in this model.

            Descriptors:  immune system, infection, pharmacology, lethal viral challenge pandemic protective immunity, induction.

Rimmelzwaan, G.F., J.C. de Jong, T.M. Bestebroer, A.M. van Loon, E.C. Claas, R.A. Fouchier, and A.D. Osterhaus (2001 ). Antigenic and genetic characterization of swine influenza A (H1N1) viruses isolated from pneumonia patients in The Netherlands. Virology 282(2): 301-6.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Descriptors:  influenza A virus, porcine genetics, influenza A virus, porcine immunology, pneumonia, viral transmission, pneumonia, viral virology, swine virology, adult, cell line, child, preschool, ferrets, hemagglutination inhibition tests, immune sera immunology, influenza A virus, porcine isolation and purification, influenza A virus, porcine metabolism, likelihood functions, molecular sequence data, Netherlands, phylogeny, sequence homology, nucleic acid.

Robertson, J.S., M.E.S.C. Robertson, and I.J. Roditi (1984). Nucleotide sequence of RNA segment 3 of the avian influenza A/FPV/Rostock/34 and its comparison with the corresponding segment of human strains A/PR/8/34 and A/NT/60/68. Virus Research 1(1): 73-79.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Descriptors:  avian influenza virus, RNA, nucleotide sequence, human strains.

Rogers, G.N. and B.L. D'Souza (1989). Receptor binding properties of human and animal H1 influenza virus isolates. Virology 173(1): 317-22.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  It has been previously reported that several human H1 influenza viruses isolated prior to 1956, in contrast to human H3 isolates which are quite specific for SA alpha 2,6Gal sequences, apparently recognize both SA alpha 2,3Gal and SA alpha 2,6Gal sequences (Rogers, G.N., and Paulson, J.C., Virology 127, 361-373, 1983). In this report human H1 isolates representative of two epidemic periods, from 1934 to 1957 and from 1977 to 1986, and H1 influenza isolated from pigs, ducks, and turkeys were compared for their ability to utilize sialyloligosaccharide structures containing terminal SA alpha 2,3Gal or SA alpha 2,6Gal sequences as receptor determinants. Five of the eight human isolates from the first epidemic period recognize both SA alpha 2,3Gal and SA alpha 2,6Gal linkages, in agreement with our previous results. Of the remaining three strains, all isolated towards the end of the first epidemic, two appear to prefer SA alpha 2,6Gal sequences while the third preferentially binds SA alpha 2,3Gal sequences. In contrast to the early isolates, 11 of 13 human strains isolated during the second epidemic period preferentially bind SA alpha 2,6Gal containing oligosaccharides. On the basis of changes in receptor binding associated with continued passage in the laboratory for some of these later strains, it seems likely that human H1 isolates preferentially bind SA alpha 2,6Gal sequences in nature, and that acquisition of SA alpha 2,3Gal-binding is associated with laboratory passage. Influenza H1 viruses isolated from pigs were predominantly SA alpha 2,6Gal-specific while those isolated from ducks were primarily SA alpha 2,3Gal-specific. Thus, as has been previously reported for H3 influenza isolates, receptor specificity for influenza H1 viruses appears to be influenced by the species from which they were isolated, human isolates binding preferentially to SA alpha 2,6Gal-containing oligosaccharides while those isolated from ducks prefer SA alpha 2,3Gal-containing oligosaccharides. However, unlike the SA alpha 2,6Gal-specific H3 isolates, binding to cell surface receptors by the H1 influenza viruses is not sensitive to inhibition by horse serum glycoproteins, regardless of their receptor specificity. These results suggest that, while the H1 and H3 hemagglutinins appear to be subject to similar host-derived selective pressures, there appear to be certain fundamental differences in the detailed molecular interaction of the two hemagglutinins with their sialyloligosaccharide receptor determinants.

            Descriptors:  influenza A virus avian metabolism, influenza A virus human metabolism, influenza A virus, porcine metabolism, influenza A virus metabolism, orthomyxoviridae metabolism, receptors, virus metabolism, ducks, hemagglutination inhibition tests, hemagglutination tests, species specificity, swine, turkeys.

Rogers, G.N. and J.C. Paulson (1983). Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127(2): 361-73.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The binding of influenza virus to erythrocytes and host cells is mediated by the interaction of the viral hemagglutinin (H) with cell surface receptors containing sialic acid (SA). The specificity of this interaction for 19 human and animal influenza isolates was examined using human erythrocytes enzymatically modified to contain cell surface sialyloligosaccharides with the sequence SA alpha 2,6Gal beta 1,4GlcNAc; SA alpha 2,3Gal beta 1,4(3)GlcNAc; SA alpha 2,3Gal beta 1,3GalNAc; or SA alpha 2,6GalNAc. Although none of the viruses agglutinated cells containing the SA alpha 2,6GalNAc linkage, differential agglutination of cells containing the other three sequences revealed at least three distinct receptor binding types. Several virus isolates exhibited marked receptor specificity, binding only to cells containing the SA alpha 2,6Gal or the SA alpha 2,3Gal linkage, while others bound equally well to cells containing either linkage. Moreover, some viruses could distinguish between two oligosaccharide receptor determinants containing the terminal SA alpha 2,3Gal linkage when present in the SA alpha 2,3Gal beta 1,4(3)GlcNAc sequence or the SA alpha 2,3Gal beta 1,3GalNAc sequence binding cells containing only the former. The observed receptor specificities were not significantly influenced by the viral neuraminidases as shown by the use of the potent neuraminidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Receptor specificity appeared, to some extent, to be dependent on the species from which the virus was isolated. In particular, human isolates of the H3 serotype all agglutinated cells containing the SA alpha 2,6Gal linkage, but not cells bearing the SA alpha 2,3Gal beta 1,3GalNAc sequence. In contrast, antigenically similar (H3) isolates from avian and equine species preferentially bound erythrocytes containing the SA alpha 2,3Gal linkage. This is of particular interest in view of the identification of the avian virus H3 hemagglutinin as the progenitor of the H3 hemagglutinin present on the current human Hong Kong viruses.

            Descriptors:  hemagglutinins viral, influenza A virus immunology, oligosaccharides metabolism, receptors, virus metabolism, hemagglutination, viral, hemagglutinin glycoproteins, influenza virus, influenza A virus avian immunology, influenza A virus human immunology, influenza A virus, porcine immunology, neuraminidase metabolism, species specificity.

Rogers, G.N., T.J. Pritchett, J.L. Lane, and J.C. Paulson (1983). Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants. Virology 131(2): 394-408.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Human and animal (avian and equine) influenza A virus isolates of the H3 serotype exhibit marked differences in their ability to bind specific sialyloligosaccharide sequences that serve as cell surface receptor determinants (G. Rogers and J. Paulson, 1983, Virology 127, 361-373). Whereas human isolates of this subtype strongly agglutinate enzymatically modified human erythrocytes containing the terminal SA alpha 2,6Gal sequence, avian and equine isolates preferentially agglutinate erythrocytes bearing the SA alpha 2, 3Gal sequence. As shown in this report, a glycoprotein found in horse serum, alpha 2-macroglobulin, is a potent inhibitor of viral adsorption to the cell surface for human H3 isolates. In contrast, avian and equine isolates are poorly inhibited suggesting a correlation between receptor specificity and inhibitor sensitivity. Growth of a human H3 isolate (A/Memphis/102/72) on MDCK cells in the presence of horse serum resulted in an overall shift in the virus receptor specificity from preferential binding of the SA alpha 2,6Gal linkage to preferential binding of the SA alpha 2,3Gal linkage characteristic of avian and equine isolates. Clonally isolated variants of A/Memphis/102/72 grown in the presence or absence of horse serum exhibited binding properties that account for those observed in the field isolates. Clones which preferentially bound the SA alpha 2,6Gal linkage, like the parent human virus, were very sensitive to inhibition of hemagglutination by horse serum and equine alpha 2-macroglobulin. In contrast, receptor variants which preferentially bound the SA alpha 2,3Gal linkage, like the avian and equine isolate, were insensitive to such inhibitors. None of the variants was very sensitive to inhibition of hemagglutination by human alpha 2-macroglobulin. These results suggest that the presence, in vivo, of a glycoprotein inhibitor such as equine alpha 2-macroglobulin could suppress infection of influenza viruses bearing an H3 hemagglutinin with a SA alpha 2,6Gal specific, inhibitor sensitive phenotype, allowing growth to predominance of a virus which is SA alpha 2,3Gal specific and inhibitor insensitive as found in avian and equine isolates.

            Descriptors:  glycoproteins antagonists and inhibitors, influenza A virus avian drug effects, influenza A virus human drug effects, influenza A virus drug effects, receptors, virus drug effects, viral proteins antagonists and inhibitors, adsorption, chick embryo, ducks, erythrocytes immunology, erythrocytes microbiology, hemagglutination inhibition tests, hemagglutination tests, hemagglutinins viral analysis, horses, alpha macroglobulins pharmacology.

Rohm, C., T. Horimoto, Y. Kawaoka, J. Suss, and R.G. Webster (1995). Do hemagglutinin genes of highly pathogenic avian influenza viruses constitute unique phylogenetic lineages? Virology 209(2): 664-670.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  Avian influenza A viruses of the H5 and H7 subtypes periodically cause severe outbreaks of disease in poultry. The question we wished to address in this study is whether these highly pathogenic strains constitute unique lineages or whether they and related nonpathogenic viruses are derived from common ancestors in the wild bird reservoir. We therefore compared the nucleotide and amino acid sequences of the hemagglutinin (HA) genes of 15 H5 and 26 H7 influenza A viruses isolated over 91 years from a variety of host species in Eurasia, Africa, Australia, and North America. Phylogenetic analysis indicated that the HA genes of H5 and H7 viruses that cause severe disease in domestic birds do not form unique lineages but share common ancestors with nonpathogenic H5 and H7 viruses. These findings predict that highly pathogenic avian H5 and H7 influenza A viruses will continue to emerge from wild bird reservoirs. Another important question is whether H7 influenza viruses found in mammalian species are derived from avian strains. We included eight equine influenza viruses and one seal isolate in the phylogenetic analysis of H7 HA genes. We could show that the HA genes of both, the equine and the seal viruses, shared ancestors with avian H7 HA genes. This indicates that currently circulating H7 viruses with an avian HA gene may have the potential to adapt to mammalian species and to cause an influenza outbreak in the new host.

            Descriptors:  avian influenza virus, agglutinins, genes, pathogenicity, phylogeny, nucleotide sequence, chemical composition, biological properties, cell structure, chromosomes, evolution, genomes, influenza virus, microbial properties, nucleus, orthomyxoviridae, proteins, viruses, viral hemagglutinins, structural genes, amino acid sequences.

Romvary, J. and J. Tanyi (1975). Occurrence of Hong Kong influenza A (H3N2) virus infection in the Budapest zoo. Acta Veterinaria Academiae Scientiarum Hungaricae 25(2-3): 251-254.

            Descriptors:  Hong Kong influenza A, epidemiology, Streptopelia decaocto, zoo animals, birds, dogs, goats, human, fowl, Budapest.

Roslaya, I.G., L.Y.A.S. Zakstel' skaya, and G.E. Roslyakov (1975). Eksperimental'noe infitsirovanie rechnykh krachek virusom grippa ptits. [Experimental infection of terns (Sterna hirunda) with a strain of avian influenza virus isolated from mallard]. Sbornik Trudov Institut Virusologii Imeni D.I. Ivanoskogo, "Ekologiya Virusov" 3 : 142-146.

            Descriptors:  avian influenza virus, orthomyxoviridae, Charadriiformes, terns, Sterna hirunda, mallard.

Rota, P.A., E.P. Rocha, M.W. Harmon, and et al (1989). Laboratory characterization of a swine influenza virus isolated from a fatal case of human influenza. Journal of Clinical Microbiology 27(6): 1413-1416.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Descriptors:  zoonoses, influenza virus A and B, relationships, RNA, Sus scrofa, pigs, swine influenza virus, Wisconsin, United States.

Rott, R. (1997). Influenza, eine besondere Form einer Zoonose. [Influenza, a special form of zoonosis]. Berliner Und Munchener Tierarztliche Wochenschrift 110(7-8): 241-6.  ISSN: 0005-9366.

            NAL Call Number:  41.8 B45

            Abstract:  Findings based on molecular genetics and phylogeny indicate that avian species represent an important reservoir for influenza viruses and that virus strains of man and different mammals originated from avian influenza virus ancestors. In contrast to infectious agents causing classical zoonoses, influenza viruses have to alter their genetic make up in order to change their host range. The special, segmented structure of the viral RNA allows an exchange of gene(s) between two different influenza viruses (reassortment) resulting in viruses with different combinations of genome segments and thereby creating new biological properties. Under the selective pressure of the new host the most adapted virus variants will succeed which arose from a genetically heterogeneous virus population with additional mutations. In particular mutations of the genes encoding the polymerase complex (mutator mutations) would be advantageous for rapid adaptation in a hostile environment. The generation of influenza viruses capable of overcoming the species barrier is a rare event since only virus variants will succeed which are genetically stable and transmissible and which replicate efficiently in the new host. It is considered likely that pigs act as intermediate hosts for adaptation of avian viruses to man.

            Descriptors:  influenza transmission, influenza veterinary, orthomyxoviridae genetics, zoonoses, birds, mammals, mutation, orthomyxoviridae pathogenicity, species specificity, swine, variation genetics.

Rott, R., H. Becht, and Orlich (1975). Antigenic relationship between the surface antigens of avian and equine influenze viruses. Medical Microbiology and Immunology 161(4): 253-61.  ISSN: 0300-8584.

            Abstract:  Influenza virus Equine 1 (A/equine/Prague/56) has a hemagglutinin which is antigenically related to the hemagglutinin of fowl plague virus strain Rostock (FPV) and a neuraminidase which cross-reacts with the enzyme of virus N (A/chick/Germany/49). After a single injection of chickens with Equine 1 virus no hemagglutination inhibiting (HI) and neutralizing antibodies against FPV can be demonstrated, although the birds are fully protected against a lethal dose of FPV. HI and neutralizing antibodies against FPV appear after a second injection of Equine 1 virus several weeks after the first one. Liberation of newly sunthesized FPV from the host cell is ingibited by antibodies cross-reacting with any antigen of virus surface.

            Descriptors:  antigens, viral administration and dosage,  arteritis virus, equine immunology, influenza A virus avian immunology, RNA viruses immunology, binding sites, antibody, epitopes, fluorescent antibody technique, hemadsorption, hemagglutination inhibition tests, hemagglutination tests, hemagglutinins viral isolation and purification, injections, intravenous, neuraminidase analysis, neutralization tests, plaque assay.

Rovnova, Z.I., E.I. Isaeva, A.L. Platonova, and P.N. Kosiakov (1989). Antigenno-geneticheskie sviazi virusov grippa cheloveka i zhivotnykh. [Antigenic-genetic connections between human and animal influenza viruses]. Voprosy Virusologii 34(5): 553-7.  ISSN: 0507-4088.

            NAL Call Number:  448.8 P942

            Abstract:  A comparative immunological analysis of the composition of antigenic determinants (AGD) in hemagglutinins of human influenza A virus (HIAV) of the serosubtypes H1, H2, H3, and in hemagglutinins of animal influenza viruses (AIV) of the serosubtypes H1, H3-H6, H8-H11 with 25 polyclonal highly active sera was demonstrated. Using original monospecific mon AGD in HIAV and AIV hemagglutinins was demonstrated. Using original monospecific antibodies to individual AGD, those AGD contributing to similarity and differences between HIAV and AIV were determined. It was found that influenza A. virus strains isolated from man in the USSR in 1986 were identical in the antigenic structure of hemagglutinin with that isolated from a tern in 1973 (A/tern/Turkmenistan/18/73).

            Descriptors:  epitopes, genes viral, influenza A virus avian immunology, human immunology, antigens, viral immunology, cross reactions, hemagglutination tests, hemagglutinins viral genetics, hemagglutinins viral immunology, avian genetics, human genetics, neuraminidase genetics, neuraminidase immunology, species specificity.

Rowe, T., R.A. Abernathy, J. Hu Primmer, W.W. Thompson, X. Lu, W. Lim, K. Fukuda, N.J. Cox, and J.M. Katz (1999). Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays. Journal of Clinical Microbiology 37(4): 937-43.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.

            Descriptors:  antibodies, viral blood, influenza A virus avian immunology, serologic tests methods, adolescent, adult, blotting, western methods, blotting, western statistics and numerical data, child, preschool, cross reactions, enzyme linked immunosorbent assay methods, enzyme linked immunosorbent assay statistics and numerical data, hemagglutination inhibition tests methods, hemagglutination inhibition tests statistics and numerical data, Hong Kong epidemiology, influenza epidemiology, influenza immunology, influenza transmission, avian classification, avian pathogenicity, middle aged, neutralization tests methods, neutralization tests statistics and numerical data, sensitivity and specificity, seroepidemiologic studies, serologic tests statistics and numerical data.

Rowe, T., D.S. Cho, R.A. Bright, L.A. Zitzow, and J.M. Katz (2003). Neurological manifestations of avian influenza viruses in mammals. Avian Diseases 47(Special Issue): 1122-1126.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  The H5N1 viruses isolated from humans in Hong Kong directly infected both mice and ferrets without prior adaptation to either host. Two representative viruses, A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486) were equally virulent in outbred ferrets but differed in their virulence in inbred mice. Both HK/483 and HK/486 replicated systemically in ferrets and showed neurologic manifestations. In contrast, intranasal infection of mice with HK/483, but not HK/486, resulted in viral spread to the brain, neurologic signs, and death. However, HK/486 was able to replicate in the brain and induce lethal disease following direct intracerebral inoculation.

            Descriptors:  infection, nervous system, avian influenza, infectious disease, respiratory system disease, viral disease, neurological infection manifestations.

Rudneva, I.A., E.I. Sklyanskaya, O.S. Barulina, S.S. Yamnikova, V.P. Kovaleva, I.V. Tsvetkova, and N.V. Kaverin (1996). Phenotypic expression of HA-NA combinations in human-avian influenza A virus reassortants. Archives of Virology 141(6): 1091-9.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  Human-avian and human-mammalian influenza A virus reassortant clones with the neuraminidase (NA) gene of the A/USSR/90/77 (H1N1) strain and hemagglutinin (HA) genes of H3, H4 and H13 subtypes had been shown in an earlier publication to produce low HA yields in the embryonated chicken eggs. The low HA titers had been shown to be due, at least in part, to the formation of virion clusters at 4 degrees C; the clustering was removed by the treatment with bacterial neuraminidase [Rudneva et al., Arch. Virol (1993) 133: 437-450]. By serial passages of the reassortants in chick embryos non-aggregating variants were selected: the variants produced HA titers of the same order as A/USSR/90/77 parent virus. The assessment of the virus yields by the analysis of the partially purified virus preparations from fixed volumes of the allantoic fluid revealed that actual virion yields of the initial reassortants were lower than the yields of their passaged variants or of the parent viruses. The passaged variant of a reassortant possessing the HA gene of A/Duck/Ukraine/1/63 (H3N2) virus differed from the original (non-passaged) reassortant and from the parent A/Duck/Ukraine/1/63 virus in the reaction with a panel of monoclonal antibodies against H3 hemagglutinin. The data suggest that some HA-NA combinations may lead to an incomplete functional match between HA and NA and to the formation of low-yield reassortants, thus representing a possible limiting factor in the emergence of new HA-NA combinations in natural conditions.

            Descriptors:  hemagglutinins viral biosynthesis, influenza A virus avian metabolism, human metabolism, neuraminidase biosynthesis, reassortant viruses metabolism, antibodies, monoclonal immunology, antibodies, viral immunology, antigens, viral immunology, cell line, chick embryo, dogs, epitopes, hemagglutinin glycoproteins, influenza virus, hemagglutinins viral genetics, avian genetics, human genetics, neuraminidase genetics, phenotype, reassortant viruses genetics, serial passage, variation genetics.

Russi Cahill, J.C., M.C. Mogdasy, R.E. Somma Moreira, and M.H. de Peluffo (1975). Counterimmunoelectrophoresis with influenza antigens. I. Use of avian plague virus to detect type-specific antibodies to influenza A in human sera. Journal of Infectious Diseases 131(1): 64-6.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Avian plague virus was used as antigen in a counterimmunoelectrophoresis technique. This virus was selected because it detects only type-specific influenza A antibodies in human sera, avoiding the possible interference of other antigens with anodic migration. The results with reference sera, as well as the correlation of positive sera found by counterimmunoelectrophoresis and complement fixation with the proposed antigen, in the absence of other types of antibodies to fowl plague virus antigen, support the conclusion that the counterimmunoelectrophoresis technique reveals type-specific antibodies. The test is more sensitive than immunodiffusion but less sensitive than complement fixation. Its sensitivity, simplicity, and rapidity make it suitable for serologic surveys of human influenza A.

            Descriptors:  antibodies, viral analysis, antigens, viral, immunoelectrophoresis, influenza immunology, influenza A virus avian immunology, antibody specificity, chick embryo, complement fixation tests, guinea pigs immunology,  immune sera, immunodiffusion.

Saito, T., W. Lim, T. Suzuki, Y. Suzuki, H. Kida, S.I. Nishimura, and M. Tashiro (2001). Characterization of a human H9N2 influenza virus isolated in Hong Kong. Vaccine 20(1-2): 125-33.  ISSN: 0264-410X.

            NAL Call Number:  QR189.V32

            Abstract:  Two H9N2 viruses were isolated, for the first time, from humans in Hong Kong in 1999. Isolation of influenza viruses with a novel subtype of the hemagglutinin (HA) drew attention of health care authorities worldwide from the view of pandemic preparedness. Sequence analysis of the HA genes reveals that HA of A/Hong Kong/1073/99 (H9N2) is most closely related to that of A/quail/HK/G1/97 (H9N2) that contains the internal genes similar to those of Hong Kong/97 (H5N1) viruses. Phylogenetic and antigenic analyses demonstrated the diversity among H9 HA. A/Hong Kong/1073/99 was shown to cause a respiratory infection in Syrian hamsters, suggesting that the virus can replicate efficiently in mammalian hosts. We developed a whole virion test vaccine with a formalin-inactivated egg-grown HK1073. Intraperitoneal administration of the vaccine twice to hamsters conferred a complete protection against challenge infection by the MDCK cell-grown homologous virus. Receptor specificity of HK1073 appeared different from that of other avian influenza viruses of H9 subtype which recognize preferentially alpha-2,3 linked sialic acid. Hemagglutination of HK1073 with guinea pig erythrocytes was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing polymers. These data suggested that HK1073 had acquired a broader host range, including humans. Together with data so far available, the present study suggested that isolation of the H9 influenza viruses from humans requires precaution against the emergence of a novel human influenza.

            Descriptors:  influenza virology, influenza A virus human isolation and purification, antigens, viral immunology, Asia, cattle, cultured cells, chick embryo, child, dogs, Europe, glycoconjugates pharmacology, guinea pigs, hamsters, hemagglutination tests, hemagglutination, viral, hemagglutinin glycoproteins, influenza virus genetics, hemagglutinin glycoproteins, influenza virus physiology, Hong Kong, horses, influenza prevention and control, influenza veterinary, avian classification, avian physiology, human classification, human genetics, human immunology, human physiology, porcine classification, porcine physiology, influenza vaccine immunology, lung virology, mesocricetus, N-acetylneuraminic acid metabolism, North America, phylogeny, poultry virology, poultry diseases virology, receptors, virus metabolism, sheep, species specificity, swine, swine diseases virology, vaccination, vaccines, inactivated, virion immunology, virus cultivation.

Samaan, G. (2005). Rumor surveillance and avian influenza H5N1. Emerging Infectious Diseases 11(3): 463-6.  ISSN: 1080-6040.

            NAL Call Number:  RA648.5.E46

            Abstract:  We describe the enhanced rumor surveillance during the avian influenza H5N1 outbreak in 2004. The World Health Organization's Western Pacific Regional Office identified 40 rumors; 9 were verified to be true. Rumor surveillance informed immediate public health action and prevented unnecessary and costly responses.

            Descriptors:  influenza prevention and control, avian influenza A virus, population surveillance methods, communication, disease outbreaks, influenza epidemiology, avian influenza epidemiology, World Health Organization.

Sambhara, S., A. Kurichh, R. Miranda, T. Tumpey, T. Rowe, M. Renshaw, R. Arpino, A. Tamane, A. Kandil, O. James, B. Underdown, M. Klein, J. Katz, and D. Burt (2001). Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function. Cellular Immunology 211(2): 143-53.  ISSN: 0008-8749.

            NAL Call Number:  QR180.C4

            Descriptors:  iscoms immunology, influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine immunology, macrophages immunology, T lymphocytes, cytotoxic immunology, antibodies, viral immunology, cross reactions, fowl plague prevention and control, influenza immunology, mice inbred BALB c, mice, inbred c57bl, mice, inbred DBA, mice, knockout, time factors.

Schafer, J., M.L. Khristova, T.L. Busse, R. Sinnecker, I.G. Kharitonenkov, C. Schrader, J. Suss, and D. Bucher (1992). Analysis of internal proteins of influenza A (H2N2) viruses isolated from birds in East Germany in 1983. Acta Virologica 36(2): 113-20.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  Proteins and RNAs of influenza A (H2N2) viruses isolated from birds in 1983 in East Germany were compared antigenically with those of H2N2 human strains. The electrophoretic mobility of the viral proteins and of the S1-treated double-stranded RNAs from two human and six avian strains, as well as the results of EIA-tests using monoclonal antibodies to their matrix protein and nucleoproteins indicate an antigenic relationship between the avian isolates and human strains of H2N2 subtype. One of the avian strains had a reduced amount of matrix protein.

            Descriptors:  antigens, viral analysis, epitopes analysis, influenza A virus avian chemistry, human chemistry, RNA viral analysis, viral matrix proteins analysis, antibodies, monoclonal, ducks, enzyme linked immunosorbent assay, East Germany.

Schafer, J.R., Y. Kawaoka, W.J. Bean, J. Suss, D. Senne, and R.G. Webster (1993). Origin of the pandemic 1957 H2 influenza A virus and the persistence of its possible progenitors in the avian reservoir. Virology 194(2): 781-8.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  H2N2 influenza A viruses caused the Asian pandemic of 1957 and then disappeared from the human population 10 years later. To assess the potential for similar outbreaks in the future, we determined the antigenicity of H2 hemagglutinins (HAs) from representative human and avian H2 viruses and then analyzed the nucleotide and amino acid sequences to determine their evolutionary characteristics in different hosts. The results of longitudinal virus surveillance studies were also examined to estimate the prevalence of avian H2 isolates among samples collected from wild ducks and domestic poultry. Reactivity patterns obtained with a large panel of monoclonal antibodies indicated antigenic drift in the HA of human H2 influenza viruses, beginning in 1962. Amino acid changes were clustered in two regions of HA1 that correspond to antigenic sites A and D of the H3 HA. By contrast, the antigenic profiles of the majority of avian H2 HAs were remarkably conserved through 1991, resembling the prototype Japan 57 (H2N2) strain. Amino acid changes were distributed throughout HA1, indicating that antibodies do not play a major role in the selection of avian H2 viruses. Phylogenetic analysis revealed two geographic site-specific lineages of avian H2 HAs: North American and Eurasian. Evidence is presented to support interregion transmission of gull H2 viruses. The human H2 HAs that circulated in 1957-1968 form a separate phylogenetic lineage, most closely related to the Eurasian avian H2 HAs. There was an increased prevalence of H2 influenza viruses among wild ducks in 1988 in North America, preceding the appearance of H2N2 viruses in domestic fowl. As the prevalence of avian H2N2 influenza viruses increased on turkey farms and in live bird markets in New York City and elsewhere, greater numbers of these viruses have come into direct contact with susceptible humans. We conclude that antigenically conserved counterparts of the human Asian pandemic strain of 1957 continue to circulate in the avian reservoir and are coming into closer proximity to susceptible human populations.

            Descriptors:  disease outbreaks, disease reservoirs, hemagglutinins viral genetics, influenza epidemiology, influenza A virus genetics, orthomyxoviridae infections epidemiology, Americas epidemiology, antibodies, monoclonal, antibodies, viral immunology, Asia epidemiology, birds microbiology, Europe epidemiology, evolution, fowl plague epidemiology, fowl plague genetics, genes viral genetics, hemagglutinin glycoproteins, influenza virus, influenza genetics, influenza A virus avian genetics, avian immunology, human genetics, human immunology, influenza A virus immunology, molecular sequence data,  orthomyxoviridae infections genetics, phylogeny, population surveillance, time factors.

Schneeberger, P.M., R.A.M. Fouchier, J.M. Broekman, S.A.G. Kemink,  F.W. Rozendaal, M.P.G. Koopmans, and A.D.M. Osterhaus (2003). A fatal case of infection with avian influenza A virus (H7N7) of a veterinarian during a highly pathogenic avian influenza outbreak in the Netherlands. Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, USA, September 14-17, 2003 43: 492.

            Descriptors:  infection, occupational health, avian influenza A virus, viral pneumonia, veterinarian, human death, Netherlands.

Scholtissek, C. (1994). Source for influenza pandemics. European Journal of Epidemiology 10(4): 455-8.  ISSN: 0393-2990.

            NAL Call Number:  RA648.5.E97

            Abstract:  There are three ways how influenza A viruses can escape the immune response in the human population: (1) By antigenic drift. This means by mutation and selection of variants under the selection pressure of the immune system. These variants have amino acid replacements mainly in the epitopes of the hemagglutinin. (2) By antigenic shift. This means replacement of at least the hemagglutinin gene of the prevailing human strain by the allelic gene of an avian influenza virus by reassortment. (3) As a rare event, direct or indirect introduction of an avian influenza virus in toto into the human population. A prior introduction of an avian virus into pigs and an adaptation to the new host might be a presupposition for its final passage to humans. In this sense the nowadays situation is reminiscent to that of about 100 years ago, when an avian virus was presumably first introduced into pigs, and from there into humans. Immediately or some time thereafter the disastrous Spanish Flu in 1918/19 had killed at least 20,000,000 people in one winter. Pandemic strains can be created by all three means, however the most common way is by reassortment. In order to recognize a pandemic strain as soon as possible a worldwide surveillance system and collaborating laboratories equipped with corresponding modern technologies are required.

            Descriptors:  disease outbreaks, influenza epidemiology, influenza virology, orthomyxoviridae genetics, antigenic variation genetics, antigens, viral genetics, birds, genes viral genetics, influenza A virus avian genetics, avian immunology, porcine genetics, porcine immunology, orthomyxoviridae immunology,  swine.

Scholtissek, C., H. Burger, P.A. Bachmann, and C. Hannoun (1983). Genetic relatedness of hemagglutinins of the H1 subtype of influenza A viruses isolated from swine and birds. Virology 129(2): 521-3.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The hemagglutinin (HA) gene of the influenza virus subtype H1N1 isolated from pigs and birds has been analyzed by the hybridization technique. According to the RNase protection data the HA genes of recent isolates from pigs in Northern Europe are genetically more closely related to those of isolates from birds in Europe and North America than to those of isolates from pigs in the United States, Taiwan, and Italy. Thus, two different H1N1 subtypes are circulating in the pig population. The results are consistent with the view that H1N1 viruses can be transmitted from birds to pigs and/or vice versa.

            Descriptors:  hemagglutinins viral genetics, influenza A virus avian genetics, porcine genetics, genetics, birds microbiology, genes viral, avian immunology, avian isolation and purification, porcine classification, porcine immunology, porcine isolation and purification, nucleic acid hybridization, swine microbiology.

Scholtissek, C., J. Stech, S. Krauss, and R.G. Webster (2002). Cooperation between the hemagglutinin of avian viruses and the matrix protein of human influenza A viruses. Journal of Virology 76(4):  1781-6.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.

            Descriptors:  hemagglutinin glycoproteins, influenza virus metabolism, influenza A virus avian genetics, human genetics, reassortant viruses, viral matrix proteins metabolism, amantadine pharmacology, antiviral agents pharmacology, cell line, dogs, drug resistance, viral, fowl plague virology, hemagglutinin glycoproteins, influenza virus genetics, influenza virology, avian drug effects, avian growth and development, avian metabolism, human drug effects, human growth and development, human metabolism, kidney cytology, kidney virology, plaque assay, poultry, viral matrix proteins genetics.

Scholtissek, C. (1995). Molecular evolution of influenza viruses. Virus Genes 11(2-3): 209-215.  ISSN: 0920-8569.

            NAL Call Number:  QH434.V57

            Abstract:  There are two different mechanisms by which influenza viruses might evolve: (1) Because the RNA genome of influenza viruses is segmented, new strains can suddenly be produced by reassortment, as happens, for example, during antigenic shift, creating new pandemic strains. (2) New viruses evolve relatively slowly by stepwise mutation and selection, for example, during antigenic or genetic drift. Influenza A viruses were found in various vertebrate species, where they form reservoirs that do not easily mix. While human influenza A viruses do not spread in birds and vice versa, the species barrier to pigs is relatively low, so that pigs might function as "mixing vessels" for the creation of new pandemic reassortants in Southeast Asia, where the probability is greatest for double infection of pigs by human and avian influenza viruses. Phylogenetic studies revealed that about 100 years ago, an avian influenza A virus had crossed the species barrier, presumably first to pigs, and from there to humans, forming the new stable human and classical swine lineages. In 1979, again, an avian virus showed up in the North European swine population, forming another stable swine lineage. The North European swine isolates from 1979 until about 1985 were genetically extremely unstable. A hypothesis is put forward stating that a mutator mutation is necessary to enable influenza virus to cross the species barrier by providing the new host with sufficient variants from which it can select the best fitting ones. As long as the mutator mutation is still present, such a virus should be able to cross the species barrier a second time, as happened about 100 years ago. Although the most recent swine isolates from northern Germany are again genetically stable, we nevertheless should be on the lookout to see if a North European swine virus shows up in the human population in the near future.

            Descriptors:  evolution and adaptation, immune system, infection, microbiology, veterinary medicine, antigenic drift evolution host infection molecular evolution pandemic reassortants phylogeny species barrier virology.

Schultz, U., W.M. Fitch, S. Ludwig, J. Mandler, and C. Scholtissek (1991). Evolution of pig influenza viruses. Virology 183(1): 61-73.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  There is evidence that the nucleoprotein (NP) gene of the classical swine virus (A/Swine/1976/31) clusters with the early human strains at the nucleotide sequence level, while at the level of the amino acid sequence, as defined by consensus amino acids and in functional tests, its NP is clearly "avian like." Therefore it was suggested that the Sw/31 NP had been recently under strong selection pressure, possibly caused by reassortment with other avian influenza genes, whose gene products have to cooperate intimately with NP (Gammelin et al., 1989. Virology 170, 71-80). This suggestion has been investigated by sequencing the genes of internal and nonstructural proteins of Sw/31. The data on these sequences and on the phylogenetic trees are not in accordance with that suggestion: all these genes cluster with the early human strains at the nucleotide level while, at the level of the amino acid sequence, most of them are more closely related to the avian strains, thus resembling NP in this respect. This indicates that these genes rather evolved concomitantly with the NP gene. Our data are in agreement with the suggestion that, at about the time of the Spanish Flu (1918/19), a human influenza A (H1N1) virus entered the pig population. Furthermore, it is known that the NP of the human influenza A viruses--in contrast to that of the avian and swine strains--has been under strong selection pressure to change (Gammelin et al., 1990. Mol. Biol. Evol. 7, 194-200. Gorman et al., 1990a. J. Virol. 64, 1487-1497). Thus, after transfer of a human strain into pigs, the selection pressure might be released, enabling the NP and the other genes of the swine virus to evolve back to the optimal avian sequences, especially at the functionally important consensus positions. The swine influenza viruses circulating since 1979 in Northern Europe--represented by A/Swine/Germany/2/81 (H1N1)--have all genes, so far examined, derived from an avian influenza virus pool and are different from the classical swine viruses.

            Descriptors:  influenza A virus, porcine genetics, phylogeny, RNA replicase, viral proteins genetics,  chick embryo, consensus sequence, genes viral, nucleoproteins genetics, swine, viral core proteins genetics.

Sears, S.D., M.L. Clements, R.F. Betts, H.F. Maassab, B.R. Murphy, and M.H. Snyder (1988). Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults. Journal of Infectious Diseases 158(6): 1209-19.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.

            Descriptors:  influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine, adult, antibodies, viral biosynthesis, cold, double blind method, enzyme linked immunosorbent assay, hemagglutination inhibition tests, avian pathogenicity, avian physiology, human pathogenicity, human physiology, random allocation, vaccines, attenuated, vaccines, synthetic, virus replication.

Shaw, M., L. Cooper, X. Xu, W. Thompson, S. Krauss, Y. Guan, N. Zhou, A. Klimov, N. Cox, R. Webster, W. Lim, K. Shortridge, and K. Subbarao (2002). Molecular changes associated with the transmission of avian influenza a H5N1 and H9N2 viruses to humans. Journal of Medical Virology 66(1): 107-14.  ISSN: 0146-6615.

            Abstract:  In order to identify molecular changes associated with the transmission of avian influenza A H5N1 and H9N2 viruses to humans, the internal genes from these viruses were compared to sequences from other avian and human influenza A isolates. Phylogenetically, each of the internal genes of all sixteen of the human H5N1 and both of the H9N2 isolates were closely related to one another and fell into a distinct clade separate from clades formed by the same genes of other avian and human viruses. All six internal genes were most closely related to those of avian isolates circulating in Asia, indicating that reassortment with human strains had not occurred for any of these 18 isolates. Amino acids previously identified as host-specific residues were predominantly avian in the human isolates although most of the proteins also contained residues observed previously only in sequences of human influenza viruses. For the majority of the nonglycoprotein genes, three distinct subgroups could be distinguished on bootstrap analyses of the nucleotide sequences, suggesting multiple introductions of avian virus strains capable of infecting humans. The shared nonglycoprotein gene constellations of the human H5N1 and H9N2 isolates and their detection in avian isolates only since 1997 when the first human infections were detected suggest that this particular gene combination may confer the ability to infect humans and cause disease. J. Med. Virol. 66:107-114, 2002. Published 2002 Wiley-Liss, Inc.

            Descriptors:  fowl plague transmission, influenza virology, influenza A virus avian genetics, human genetics, fowl plague virology, influenza transmission, avian classification, human classification, human isolation and purification, molecular sequence data, nasopharynx virology, phylogeny, viral proteins genetics.

Shinshaw, V.S., R.G. Webster, and W.J. Bean. (1981). Application of recently developed techniques to determine the origin of influenza A viruses appearing in avian and mammalian species and to develop potent avian influenza vaccines. In: Proceedings of the First International Symposium on Avian Influenza, Beltsville, Maryland, USA, p. 134-147.

            NAL Call Number: aSF995.6.I6I5 1981a

            Descriptors: avian influenza virus, techniques, vaccines, mammalian species, avian species.

Shinya, K., F.D. Silvano, T. Morita, A. Shimada, M. Nakajima, T. Ito, K. Otsuki, and T. Umemura (1998). Encephalitis in mice inoculated intranasally with an influenza virus strain originated from a water bird. Journal of Veterinary Medical Science the Japanese Society of Veterinary Science 60(5): 627-9.  ISSN: 0916-7250.

            NAL Call Number:  SF604.J342

            Abstract:  Five-week-old ddY mice were inoculated intranasally with a low virulent (4e) or highly virulent (24a5b) avian influenza virus strain originated from a water bird. None of mice in the 4e group showed clinical signs and brain lesions. Of the 24a5b group, two mice died and one mouse was killed at a moribund state at day 7 post-inoculation (PI). Four mice of the 24a5b group necropsied at day 5 or 7 PI had mild to severe encephalitis in the brain stem and the cerebellar white matter. Influenza virus antigen was detected in neurons, glial cells and vascular endothelium in the lesions. The distribution of the lesions seems to indicate the transneuronal invasion of the virus via cranial nerve fibers into the brain.

            Descriptors:  birds virology, brain pathology, encephalitis, viral pathology, influenza pathology, influenza A virus avian pathogenicity, antigens, viral analysis, brain virology, brain stem pathology, cerebellum pathology, encephalitis, viral virology, immunohistochemistry, avian isolation and purification, mice, necrosis, virulence.

Shortridge, K.F. (1982). Avian influenza A viruses of southern China and Hong Kong: ecological aspects and implications for man. Bulletin of the World Health Organization 60(1): 129-35.  ISSN: 0042-9686.

            NAL Call Number:  449.9 W892B

            Descriptors:  influenza A virus avian isolation and purification, chickens, China, ducks, geese, hemagglutination inhibition tests, Hong Kong, neuraminidase analysis, poultry.

Shortridge, K.F. (1992). Pandemic influenza: a zoonosis? Seminars in Respiratory Infections 7(1): 11-25.  ISSN: 0882-0546.

            Abstract:  In the last two decades, influenza A viruses have been found to occur throughout the animal kingdom, mainly in birds, notably aquatic ones, in which infection is largely intestinal, waterborne, and asymptomatic. The domestic duck of southern China, raised in countless numbers all year round mainly as an adjunct to rice farming, is the principal host of influenza A viruses. Studies based on Hong Kong H3N2 viruses from southern China suggest that pandemic strains originate from the domestic duck there and are transmitted to humans via the domestic pig, which acts as a "mixing vessel" for two-way transmission of viruses. This provides further support for the hypothesis that the region is a hypothetical influenza epicenter. Rural dwellers in the epicenter show serological evidence of contact with non-human influenza A viruses. Two hypotheses are advanced for the range of hemagglutinin (HA) subtypes of viruses that can cause pandemics (1) circle or cycle limited to H1, H2, and H3 subtypes, thereby implying that a virus of the H2 subtype will cause the next pandemic; and (2) spiral, by which any one of the 14 HA subtypes recorded to date may be involved. Consideration is given to the temporal and geographical factors and range of hosts, namely the duck, pig, and human, that need to be submitted to virus surveillance in China and beyond to attempt to anticipate a future pandemic. Evidence is presented that points strongly to pandemic influenza being a zoonosis.

            Descriptors:  ducks microbiology, influenza transmission, influenza A virus avian pathogenicity, human pathogenicity, porcine pathogenicity, swine microbiology, zoonoses transmission, China epidemiology, chronology, disease outbreaks prevention and control, feces microbiology, fresh water, influenza epidemiology, influenza microbiology, avian isolation and purification, human isolation and purification, porcine isolation and purification, reassortant viruses genetics.

Shortridge, K.F., P. Gao, Y. Guan, T. Ito, Y. Kawaoka, D. Markwell, A. Takada, and R.G. Webster (2000). Interspecies transmission of influenza viruses: H5N1 virus and a Hong Kong SAR perspective. Veterinary Microbiology 74(1-2): 141-7.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Abstract:  This account takes stock of events and involvements, particularly on the avian side of the influenza H5N1 'bird flu' incident in Hong Kong SAR in 1997. It highlights the role of the chicken in the many live poultry markets as the source of the virus for humans. The slaughter of chicken and other poultry across the SAR seemingly averted an influenza pandemic. This perspective from Hong Kong SAR marks the coming-of-age of acceptance of the role of avian hosts as a source of pandemic human influenza viruses and offers the prospect of providing a good baseline for influenza pandemic preparedness in the future. Improved surveillance is the key. This is illustrated through the H9N2 virus which appears to have provided the 'replicating' genes for the H5N1 virus and which has since been isolated in the SAR from poultry, pigs and humans highlighting its propensity for interspecies transmission.

            Descriptors:  influenza transmission, influenza A virus avian pathogenicity, zoonoses transmission, chickens, disease outbreaks prevention and control, fowl plague transmission, Hong Kong epidemiology, influenza mortality, influenza virology, avian genetics.

Shortridge, K.F., A.P. King, and R.G. Webster (1987). Monoclonal antibodies for characterizing H3N2 influenza viruses that persist in pigs in China. Journal of Infectious Diseases 155(3): 577-81.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  antigens, viral immunology, influenza A virus, porcine immunology, influenza A virus immunology, swine microbiology, viral core proteins, antibodies, monoclonal immunology, antibodies, viral immunology, antigens, viral analysis, China, cross reactions, epitopes, hemagglutinins viral immunology, Hong Kong, avian immunology, human immunology, neuraminidase immunology, nucleoproteins immunology, Taiwan, viral proteins immunology.

Shortridge, K.F., J.S.M. Peiris, and Y. Guan (2003). The next influenza pandemic: Lessons from Hong Kong. Society for Applied Microbiology Symposium Series (32): 70S-79S.  ISSN: 1467-4734.

            NAL Call Number:  QR1.S64

            Abstract:  Pandemic influenza is a zoonosis. Studies on influenza ecology conducted in Hong Kong since the 1970s in which Hong Kong essentially functioned as an influenza sentinel post indicated that it might be possible, for the first time, to have influenza preparedness at the baseline avian level. This appreciation of influenza ecology facilitated recognition of the H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of virus for humans and, if so, was the first instance where a pandemic may have been averted. The 2001 and 2002 H5N1 incidents demonstrated that it was possible to have an even higher order of baseline preparedness with the recognition in chicken of a range of genotypes of H5N1-like viruses before they had the opportunity to infect humans. Investigations of these incidents revealed a complex ecology involving variously precursor avian H5N1 virus in geese and ducks, and H9N2 and H6N1 viruses in quail, the quail possibly functioning as an avian 'mixing vessel' for key genetic reassortment events for onward transmission of H5N1 viruses highly pathogenic for chicken and humans. These findings highlight the importance of systematic virus surveillance of domestic poultry in recognizing changes in virus occurrence, host range and pathogenicity as signals at the avian level that could presage a pandemic. For example, there is now an increasing prevalence of avian influenza viruses in terrestrial (in contrast to aquatic) poultry. Prior to 1997, no particular virus subtype other than H4N6 would have been considered a candidate for pandemicity and this was based, in the absence of any other data, on its high frequency of occurrence in ducks in southern China. Now, with the isolation of H5N1 and H9N2 viruses from humans supported by genetic, molecular and biological studies on these and other avian isolates, there is credible evidence for the candidacy, in order, of H5N1, H9N2 and H6N1 viruses. These viruses have been made available for the production of diagnostic reagents and exploratory vaccines. The 1997 incident upheld the hypothesis that southern China is an epicentre for the emergence of pandemic influenza viruses. However, the intensification of the poultry (chicken) industry worldwide coupled with the spread of viruses such as the Eurasian lineage of H9N2 suggest that the genesis of a pandemic could take place elsewhere in the world. This re-emphasizes the importance of systematic virus surveillance of poultry globally for international public health and for economic and food concerns. Faced with an incipient pandemic in 1997, Hong Kong brought in international experts to join the investigative effort. Good teamwork at all levels is essential in dealing with the many facets. The threat of a pandemic should not be minimized, nor should governments be lulled into a sense of false security. The media is a powerful channel and has the responsibility and the avenues to convey and influence public perception of events. Close liaison between the media and those on the operational side ensures effective, accurate and timely dissemination of information. This will enhance public confidence in the investigative process and in steps taken for its safety and health.

            Descriptors:  epidemiology, infection, public health, respiratory system, influenza, respiratory system disease, viral disease, epidemics, pandemics, viral occurrence.

Shu, L.L., W.J. Bean, and R.G. Webster (1993). Analysis of the evolution and variation of the human influenza A virus nucleoprotein gene from 1933 to 1990. Journal of Virology 67(5): 2723-9.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  This study examined the evolution and variation of the human influenza virus nucleoprotein gene from the earliest isolates to the present. Phylogenetic reconstruction of the most parsimonious evolutionary path connecting 49 nucleoprotein sequences yielded a single lineage. The average calculated rate of mutation was 3.6 nucleotide substitutions per year (2.3 x 10(-3) substitutions per site per year). Thirty-two percent of these mutations resulted in amino acid substitutions, and the remainder were silent mutations. Analysis of virus isolates from China and elsewhere showed no significant differences in their rate of evolution, genetic diversity, or mean survival time. The nearly constant rate of change was maintained through the two antigenic shifts, and there were no obvious changes in the number or types of mutations associated with the changes in the surface proteins. A detailed comparison of the changes that have occurred on the main evolutionary path with those that have occurred on the side branches of the phylogenetic tree was made. This showed that while 35% of the mutations on the side branches resulted in amino acid changes, only 21% of those on the main path affected the protein sequence. These results suggest that although the rate of change of the human influenza virus nucleoprotein is much higher than that previously described for avian influenza viruses, there are measurable constraints on the evolution of the surviving virus lineage. Comparison of the nucleoproteins of virus isolates adapted to chicken embryos with the nucleoproteins of those grown only in MDCK cells revealed no consistent differences between the virus pairs. Thus, although the nucleoprotein is known to be critical for host specificity, its adaptation to growth in eggs apparently involves no immediate selective pressures, such as are found with hemagglutinin.

            Descriptors:  evolution, genes viral genetics, influenza A virus human genetics, nucleoproteins, viral core proteins genetics, amino acid sequence, cultured cells, chick embryo, cloning, molecular, molecular sequence data, mutagenesis, polymerase chain reaction, sequence analysis, DNA, sequence homology, amino acid, time factors, variation genetics.

Shu, L.L., Y.P. Lin, S.M. Wright, K.F. Shortridge, and R.G. Webster (1994). Evidence for interspecies transmission and reassortment of influenza A viruses in pigs in Southern China. Virology 202(2): 825-833.  ISSN: 0042-6822.

            NAL Call Number:  448.8 V81

            Abstract:  The Asian/57, Hong Kong/68, and Russian/77 pandemics of this century appeared or reappeared in China. Interspecies transmission and genetic reassortment of influenza viruses have been implicated in the origin of these human pandemic influenzas viruses. Pigs have been suspected to be the "mixing vessel" where reassortment occurs. To investigate this possibility, 104 porcine influenza viruses collected at random from Southern China from 1976 to 1982, including 32 H3N2 isolates and 72 H1N1 isolates, were studied using dot blot hybridization, partial sequencing, and phylogenetic analysis. There were 29 of 32 H3N2 isolates characteristic of viruses originally derived from humans; the other 3 isolates were reassortants containing genes from porcine and human influenza viruses. Phylogenetic analyses of the polymerase B1 (PB1) genes showed that interspecies transmission from humans to pigs has happened multiple times in pigs in Southern China. All 72 H1N1 isolates were of porcine origin characteristic of classical porcine H1N1 influenza virus. Analysis of 624 genes of porcine influenza viruses from Southern China failed to detect any evidence for avian influenza virus genes. This contrasts to what is currently found in Europe, where the majority of porcine influenza virus isolates are of avian origin.

            Descriptors:  swine, Guangdong, Hong Kong, Taiwan, mankind,  influenza virus, swine influenza virus, disease transmission, hosts, provenance, phylogeny, genes, artiodactyla, Asia, biological competition, cell structure, China, chromosomes, domestic animals, East Asia, evolution, influenza virus, livestock, mammals, nucleus,  parasitism, pathogenesis, suidae, useful animals, viruses, pandemics, genetic reassortment, virus mixing vessels, man.

Shu, L.P., G.B. Sharp, Y.P. Lin, E.C.J. Class, S.L. Krauss, K.F. Shortridge, and R.G. Webster (1996). Genetic reassortment in pandemic and interpandemic influenza viruses: A study of 122 viruses infecting humans. European Journal of Epidemiology 12(1): 63-70.  ISSN: 0393-2990.

            NAL Call Number:  RA648.5.E97

            Abstract:  The human influenza pandemics of 1957 and 1968 were caused by reassortant viruses that possessed internal gene segments from avian and human strains. Whether genetic reassortment of human and avian influenza viruses occurs during interpandemic periods and how often humans are infected with such reassortants is not known. To provide this information, we used dot-blot hybridization, partial nucleotide sequencing and subsequent phylogenetic analysis to examine the 6 internal genes of 122 viruses isolated in humans between 1933 and 1992 primarily from Asia, Europe, and the Americas. The internal genes of A/New Jersey/11/76 isolated from a human fatality at Fort Dix, New Jersey in 1976 were found to be of porcine origin. Although none of the geographically and temporally diverse collection of 122 viruses was an avian-human or other reassortant, cognizance was made of the fact that there were two isolates from children from amongst 546 influenza A isolates obtained from The Netherlands from 1989-1994 which were influenza A reassortants containing genes of avian origin, viruses which have infected European pigs since 1983-1985. Thus, genetic reassortment between avian and human influenza strains does occur in the emergence of pandemic and interpandemic influenza A viruses. However, in the interpandemic periods the reassortants have no survival advantage, and the circulating interpandemic influenza viruses in humans do not appear to accumulate avian influenza virus genes.

            Descriptors:  epidemiology, genetics, infection, microbiology, public health, genetic reassortment genetics infection internal genes interpandemic influenza virus interspecies transmission pandemic influenza virus pathogen virology zoonotic infections.

Silim, A. (2003). Avian Influenza (H5N1): a menace for humans? State of things [L'influenza aviaire (H5N1): une menace pour les humains? Etat de la question]. Medecin Veterinaire Du Quebec  33(3): 122 123.

            NAL Call Number:  SF602.M8

            Descriptors:  avian influenza virus, human, zoonoses, diagnosis, disease distribution, disease prevalence, disease transmission, epidemiology, poultry, zoonoses.

Simpson, V.R. (2002). Wild animals as reservoirs of infectious diseases in the UK. Veterinary Journal 163(2): 128-146.  ISSN: 1090-0233.

            NAL Call Number:  SF601.V484

            Abstract:  This review aims to illustrate the extent to which wildlife act as reservoirs of infectious agents that cause disease in domestic stock, pet and captive animals and humans. More than 40 agents are described. In the case of some of these, e.g. Cryptosporidium spp., Escherichia coli O157 and malignant catarrhal fever, the current evidence is that wildlife either does not act as a reservoir or is of limited importance. However, in the case of many important diseases, including bovine tuberculosis, Weil's disease, Lyme disease, avian influenza, duck virus enteritis and louping ill, wild animals are considered to be the principal source of infection. Wildlife may be involved in the epidemiology of other major diseases, such as neosporosis, Johne's disease, mucosal disease and foot and mouth disease, but further studies are needed. The UK would benefit from a more positive approach to the study of wildlife and the infections they harbour.

            Descriptors:  epidemiology, infection, vector biology, veterinary medicine, Cryptosporidium infection, parasitic disease, transmission, Escherichia coli infection, bacterial disease, transmission, Johne's disease, infectious disease, Lyme disease, bacterial disease, Weil's disease, bacterial disease, avian influenza, viral disease, bovine tuberculosis, bacterial disease, duck virus enteritis, digestive system disease, viral disease, foot and mouth disease, viral disease, malignant catarrhal fever, bacterial disease, neoplastic disease, mucosal disease, infectious disease, neosporosis, infectious disease.

Sims, L. (2000). Did Hong Kong H5N1 really threaten human health? World Poultry (Special): 13-14.  ISSN: 1388-3119.

            NAL Call Number:  SF481.M54

            Descriptors:  avian influenza virus, poultry, zoonoses, disease transmission, human, Hong Kong.

Slingenbergh, J.I., M. Gilbert, K.I. de Balogh, and W. Wint (2004). Ecological sources of zoonotic diseases.  Revue Scientifique Et Technique Office International Des Epizooties 23(2): 467-84.  ISSN: 0253-1933.

            NAL Call Number:  SF781.R4

            Abstract:  Although of zoonotic origin, pathogens or infections posing a global threat to human health such as human immunodeficiency virus, severe acute respiratory syndrome or emerging influenza type A viruses may actually have little in common with known, established zoonotic agents, as these new agents merely underwent a transient zoonotic stage before adapting to humans. Evolution towards person-to-person transmission depends on the biological features of the pathogen, but may well be triggered or facilitated by external factors such as changes in human exposure. Disease emergence may thus be depicted as an evolutionary response to changes in the environment, including anthropogenic factors such as new agricultural practices, urbanisation, or globalisation, as well as climate change. Here the authors argue that in the case of zoonotic diseases emerging in livestock, change in agricultural practices has become the dominant factor determining the conditions in which zoonotic pathogens evolve, spread, and eventually enter the human population. Livestock pathogens are subjected to pressures resulting from the production, processing and retail environment which together alter host contact rate, population size and/or microbial traffic flows in the food chain. This process is illustrated by two study cases: a) livestock development in the 'Eurasian ruminant street' (the area extending from central Asia to the eastern Mediterranean basin) and the adjacent Arabian peninsula b) poultry production in Southeast Asia. In both scenarios, environmental factors relating to demography, land pressure and imbalances in production intensification have led to an unstable epidemiological situation, as evidenced by the highly pathogenic avian influenza upsurge early in 2004, when the main outbreaks were located in areas which had both large scale, peri-urban commercial holdings and a high density of smallholder poultry units.

            Descriptors:  physiological adaptation, agriculture methods, animal diseases epidemiology, animal diseases transmission, animal husbandry methods, animals, environment, molecular evolution, humans, population density, population dynamics, world health, zoonoses.

Smirnov, Y.A., A.S. Lipatov, A.K. Gitelman, E.C. Claas, and A.D. Osterhaus (2000). Prevention and treatment of bronchopneumonia in mice caused by mouse-adapted variant of avian H5N2 influenza A virus using monoclonal antibody against conserved epitope in the HA stem region. Archives of Virology 145(8): 1733-41.  ISSN: 0304-8608.

            NAL Call Number:  448.3 Ar23

            Abstract:  The effects of monoclonal antibody (MAb) C179 recognizing a conformational epitope in the middle of the hemagglutinine (HA) stem region were examined in a mouse model in the experiments of prevention and treatment of lethal bronchopneumonia caused by influenza A virus of H5 subtype. To model the lethal infection, avian nonpathogenic strain A/mallard duck/Pennsylvania/10218/84 (H5N2) was adapted to mice. This resulted in highly pathogenic pneumovirulent mouse-adapted (MA) variant, which was characterized. Three amino acid changes were found in the HA1 subunit of HA of MA virus. One of these was located inside the region of the conformational epitope recognized by MAb C179. However, this substitution was not significant for the recognition of HA and virus neutralization by MAb C179 in vitro and in vivo. Intraperitoneal administration of two different concentrations of MAb C179 one day before or two days after the virus challenge significantly decreased mortality rate. These results suggest that MAb C179 is efficient not only in the prevention and treatment of H1 and H2 influenza virus bronchopneumonia, as was reported previously, but also of H5-induced bronchopneumonia as well, and demonstrate in vivo the existence of a common neutralizing epitope in the HAs of these three subtypes.

            Descriptors:  antibodies, monoclonal therapeutic use, antibodies, viral therapeutic use, bronchopneumonia therapy, hemagglutinin glycoproteins, influenza virus immunology, influenza A virus avian genetics, pneumonia, viral therapy, antibodies, monoclonal pharmacology, antibodies, viral pharmacology, bronchopneumonia prevention and control, bronchopneumonia virology, cell line, disease models, animal, dose response relationship, drug, epitopes genetics, epitopes immunology, hemagglutinin glycoproteins, influenza virus genetics, avian drug effects, avian immunology, mice, molecular sequence data, neutralization tests, pneumonia, viral prevention and control, pneumonia, viral virology, sensitivity and specificity.

Smirnov, Y.A., A.S. Lipatov, R. Van Beek, A.K. Gitelman, A.D. Osterhaus, and E.C. Claas (2000). Characterization of adaptation of an avian influenza A (H5N2) virus to a mammalian host. Acta Virologica 44(1):  1-8.  ISSN: 0001-723X.

            NAL Call Number:  448.3 AC85

            Abstract:  We have used the mouse model to monitor the acquisition of virulence of a non-pathogenic influenza A virus upon adaptation to a new mammalian host. An avian strain, A/Mallard duck/Pennsylvania/10218/84 (H5N2) (Mld/PA/84) was adapted to mice by 23 serial lung-to-lung passages until a highly virulent mouse-adapted (MA) variant (Mld/PA/84-MA) emerged. This MA variant was characterized and compared to the parental strain as well as some of its intermediate passage variants. MA variant caused bronchopneumonia in mice with a high mortality rate (the virulence of Mld/PA/84-MA measured as log (EID50/LD50) was 1.75), while the parental, avirulent strain Mld/PA/84 did not cause illness and mortality in mice (log (EID50/LD50) was 7.25). Hemagglutination-inhibition (HAI) test with a set of hemagglutinin- (HA) specific monoclonal antibodies (MAbs) revealed antigenic differences between the parental strain and MA variant. Mld/PA/84-MA reacted with HA-specific MAbs in higher titers than the parental strain. The HA genes of the parental strain Mld/PA/84, the 1st, 3rd, 8th, and 15th intermediate passage variants, and Mld/PA/84-MA were sequenced. Three amino acid changes at positions 203, 273 and 320 were determined in the HA of MA variant. The first of them, Leu-->Pro (320), appeared in the HA stem region at the 8th passage. Two other in the HA1 globular region (Ser-->Phe (203) and Glu-->Gly (273)) appeared at the 15th passage. All of these substitutions were associated with the increase of viral infectivity for mouse lungs and changes in the HA antigenicity. The potential role of these changes in HA with respect to the process of viral interspecies transmission and acquisition of virulence for new host is discussed.

            Descriptors:  adaptation, physiological genetics, bronchopneumonia virology, influenza A virus avian pathogenicity, amino acid substitution, antigenic variation, chick embryo, genes viral, hemagglutination tests, hemagglutinins viral genetics, hemagglutinins viral immunology, hydrogen-ion concentration, avian genetics, avian immunology, lung immunology, lung microbiology, mice, molecular sequence data,  virulence.

Snyder, M.H., A.J. Buckler White, W.T. London, E.L. Tierney, and B.R. Murphy (1987). The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys. Journal of Virology 61(9):  2857-63.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Reassortant viruses which possessed the hemagglutinin and neuraminidase genes of wild-type human influenza A viruses and the remaining six RNA segments (internal genes) of the avian A/Pintail/Alberta/119/79 (H4N6) virus were previously found to be attenuated in humans. To study the genetic basis of this attenuation, we isolated influenza A/Pintail/79 X A/Washington/897/80 reassortant viruses which contained human influenza virus H3N2 surface glycoprotein genes and various combinations of avian or human influenza virus internal genes. Twenty-four reassortant viruses were isolated and first evaluated for infectivity in avian (primary chick kidney [PCK]) and mammalian (Madin-Darby canine kidney [MDCK]) tissue culture lines. Reassortant viruses with two specific constellations of viral polymerase genes exhibited a significant host range restriction of replication in mammalian (MDCK) tissue culture compared with that in avian (PCK) tissue culture. The viral polymerase genotype PB2-avian (A) virus, PB1-A virus, and PA-human (H) virus was associated with a 900-fold restriction, while the viral polymerase genotype PB2-H, PB1-A, and PA-H was associated with an 80,000-fold restriction of replication in MDCK compared with that in PCK. Fifteen reassortant viruses were subsequently evaluated for their level of replication in the respiratory tract of squirrel monkeys, and two genetic determinants of attenuation were identified. First, reassortant viruses which possessed the avian influenza virus nucleoprotein gene were as restricted in replication as a virus which possessed all six internal genes of the avian influenza A virus parent, indicating that the nucleoprotein gene is the major determinant of attenuation of avian-human A/Pintail/79 reassortant viruses for monkeys. Second, reassortant viruses which possessed the viral polymerase gene constellation of PB2-H, PB1-A, and PA-H, which was associated with the greater degree of host range restriction in vitro, were highly restricted in replication in monkeys. Since the avian-human influenza reassortant viruses which expressed either mode of attenuation in monkeys replicated to high titer in eggs and in PCK tissue culture, their failure to replicate efficiently in the respiratory epithelium of primates must be due to the failure of viral factors to interact with primate host cell factors. The implications of these findings for the development of live-virus vaccines and for the evolution of influenza A viruses in nature are discussed.

            Descriptors:  genes viral, influenza A virus genetics, nucleoproteins genetics, RNA directed DNA polymerase genetics, viral core proteins, viral proteins genetics, genotype, influenza A virus pathogenicity, phenotype, saimiri, temperature, virulence, virus replication.

Snyder, M.H., M.L. Clements, R.F. Betts, R. Dolin, A.J. Buckler White, E.L. Tierney, and B.R. Murphy (1986). Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers. Journal of Clinical Microbiology 23(5): 852-7.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  An avian-human reassortant influenza A virus deriving its genes coding for the hemagglutinin and neuraminidase from the human influenza A/Washington/897/80 (H3N2) virus and its six "internal" genes from the avian influenza A/Mallard/NY/6750/78 (H2N2) virus (i.e., a six-gene reassortant) was previously shown to be safe, infectious, nontransmissible, and immunogenic as a live virus vaccine in adult humans. Two additional six-gene avian-human reassortant influenza viruses derived from the mating of wild-type human influenza A/California/10/78 (H1N1) and A/Korea/1/82 (H3N2) viruses with the avian influenza A/Mallard/NY/78 virus were evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:8) adult volunteers for safety, infectivity, and immunogenicity to determine whether human influenza A viruses can be reproducibly attenuated by the transfer of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The 50% human infectious dose was 10(4.9) 50% tissue culture infectious doses for the H1N1 reassortant virus and 10(5.4) 50% tissue culture infectious doses for the H3N2 reassortant virus. Both reassortants were satisfactorily attenuated with only 5% (H1N1) and 2% (H3N2) of infected vaccines receiving less than 400 50% human infectious doses developing illness. Consistent with this level of attenuation, the magnitude of viral shedding after inoculation was reduced 100-fold (H1N1) to 10,000-fold (H3N2) compared with that produced by wild-type virus. The duration of virus shedding by vaccines was one-third that of controls receiving wild-type virus. At 40 to 100 50% human infectious doses, virus-specific immune responses were seen in 77 to 93% of volunteers. When vaccinees who has received 10(7.5) 50% tissue culture infectious doses of the H3N2 vaccine were experimentally challenged with a homologous wild-type human virus only 2 of 19 (11%) vaccinees became ill compared with 7 of 14 (50%) unvaccinated seronegative controls ( P < 0.025; protective efficacy, 79%). Thus, three different virulent human influenza A viruses have been satisfactorily attenuated by the acquisition of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The observation that this donor virus can reproducibly attenuate human influenza A viruses indicates that avian-human influenza A reassortants should be further studied as potential live influenza A virus vaccines.

            Descriptors:  hemagglutinins viral immunology, influenza A virus avian immunology, human immunology, neuraminidase immunology, viral vaccines immunology, adult, antibodies, viral biosynthesis, avian growth and development, human growth and development, virus replication.

Snyder, M.H., M.L. Clements, D. Herrington, W.T. London, E.L. Tierney, and B.R. Murphy (1986). Comparison by studies in squirrel monkeys, chimpanzees, and adult humans of avian-human influenza A virus reassortants derived from different avian influenza virus donors. Journal of Clinical Microbiology 24(3): 467-9.  ISSN: 0095-1137.

            NAL Call Number:  QR46.J6

            Abstract:  We evaluated the abilities of three different avian influenza A viruses to attenuate the wild-type human influenza A/Korea/1/82 (H3N2) virus in squirrel monkeys, chimpanzees, and adult seronegative human volunteers. Two of these, avian influenza A/Mallard/NY/78 and A/Mallard/Alberta/76 viruses, appeared to be satisfactory donors of attenuating genes for the production of live influenza A reassortant virus vaccines for human use because the reassortants exhibited an acceptable balance between attenuation and immunogenicity.

            Descriptors:  influenza A virus avian immunology, human immunology, influenza vaccine immunology, antibodies, viral biosynthesis, avian genetics, avian physiology, human genetics, human physiology, Pan troglodytes, recombination, genetic, saimiri, vaccines, attenuated, virus replication.

Snyder, M.H., E.H. Stephenson, H. Young, C.G. York, E.L. Tierney, W.T. London, R.M. Chanock, and B.R. Murphy (1986). Infectivity and antigenicity of live avian-human influenza A reassortant virus: comparison of intranasal and aerosol routes in squirrel monkeys. Journal of Infectious Diseases 154(4): 709-11.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Descriptors:  antibodies, viral biosynthesis, influenza A virus avian immunology, human immunology, influenza vaccine immunology, administration, intranasal, aerosols, immunization, avian pathogenicity, human pathogenicity, saimiri, vaccines, attenuated, virulence.

Sokolova, N.L. (1974). Dynamics of the formation of antihaemagglutinins to various types of avian influenza virus in the serum of sheep. Sbornik Nauchnykh Trudov Moskovskaya Veterinarnaya Akademiya 73(Pt. 1): 148-149.

            Descriptors:  avian influenza virus, antibodies, immune serum, immunization, sheep serum, antihemagglutinins.

Stech, J., X. Xiong, C. Sholtissek, and R.G. Webster (1999). Independence of evolutionary and mutational rates after transmission of avian influenza viruses to swine. Journal of Virology 73(3): 1878-1884.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In 1979, an H1N1 avian influenza virus crossed the species barrier, establishing a new lineage in European swine. Because there is no direct or serologic evidence of previous H1N1 strains in these pigs, these isolates provide a model for studying early evolution of influenza viruses. The evolutionary rates of both the coding and noncoding changes of the H1N1 swine strains are higher than those of human and classic swine influenza A viruses. In addition, early H1N1 swine isolates show a marked  plaque heterogeneity that consistently appears after a few passages. The presence of a mutator mutation was postulated (C. Scholtissek, S. Ludwig, and W. M. Fitch, Arch. Virol. 131:237-250, 1993) to account for these observations and the successful establishment of an avian H1N1 strain in swine. To address this question, we calculated the mutation rates of A/Mallard/New York/6750/78 (H2N2) and A/Swine/Germany/2/81 (H1N1) by using the frequency of amantadine-resistant mutants. To account for the  inherent variability of estimated mutation rates, we used a probabilistic model for the statistical analysis. The resulting estimated mutation rates of the two strains were not significantly different. Therefore, an increased mutation rate due to the presence of a mutator mutation is unlikely to have led to the successful introduction of avian H1N1 viruses in European swine.

            Descriptors:  evolution and adaptation, infection, molecular genetics, evolutionary rates, independence mutational rates, independence viral transmission.

Steinhoff, M.C., N.A. Halsey, L.F. Fries, M.H. Wilson, J. King, B.A. Burns, R.K. Samorodin, V. Perkis, B.R. Murphy, and M.L. Clements (1991). The A/Mallard/6750/78 avian-human, but not the A/Ann Arbor/6/60 cold-adapted, influenza A/Kawasaki/86 (H1N1) reassortant virus vaccine retains partial virulence for infants and children. Journal of Infectious Diseases 163(5): 1023-8.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Characteristics of avian-human (ah) and cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant vaccine viruses were compared in 37 seronegative adults and 122 seronegative infants and children. The 50% human infectious dose (HID50) in infants and children was 10(2.9) and 10(2.6) TCID50 for the ah and ca vaccine, respectively. The ah influenza A/Kawasaki/9/86 reassortant was reactogenic: 24% of infants and children infected with greater than or equal to 100 HID50 had fever greater than or equal to 39.4 degrees C. Since H3N2 ah vaccines were previously shown to be adequately attenuated, it is reasonable to suggest that the genes that code for hemagglutinin and neuraminidase of the H1N1 virus apparently influence the reactogenicity of reassortant viruses derived from the avian influenza A/Mallard/New York/6750/78 donor virus. Because this avian virus does not reproducibly confer a satisfactory level of attenuation to each subtype of influenza A virus, it is not a suitable donor virus for attenuation of wild-type influenza viruses. In contrast, the ca A/Ann Arbor/6/60 donor virus reliably confers attenuation characteristics to a variety of H1N1 and H3N2 influenza A viruses.

            Descriptors:  influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine adverse effects, adult, child, preschool, infant, influenza etiology, avian pathogenicity, human pathogenicity, vaccines, attenuated adverse effects, vaccines, synthetic adverse effects, virulence.

Steinhoff, M.C., N.A. Halsey, M.H. Wilson, B.A. Burns, R.K. Samorodin, L.F. Fries, B.R. Murphy, and M.L. Clements (1990). Comparison of live attenuated cold-adapted and avian-human influenza A/Bethesda/85 (H3N2) reassortant virus vaccines in infants and children. Journal of Infectious Diseases 162(2): 394-401.  ISSN: 0022-1899.

            NAL Call Number:  448.8 J821

            Abstract:  Randomized, placebo-controlled studies with 10(3)-10(7) 50% tissue-culture infectious dose (TCID50) of avian-human (ah) and cold-adapted (ca) influenza A/Bethesda/85 (H3N2) reassortant viruses were completed in 106 seronegative young children 6-48 months of age. Although the reassortants differed in six of eight RNA segments, they exhibited similar properties in level of attenuation, infectivity, immunogenicity, and efficacy. The 50% human infectious dose was 10(4.6) TCID50 for ah and 10(4.4) for ca vaccines. Both reassortants were satisfactorily attenuated with restricted replication and were no more reactogenic than placebo. The mean peak titer of virus shed was 10(1.5) (ah) to 10(2.0) (ca) TCID50/ml, and each of 37 isolates tested retained their characteristic vaccine phenotypes. Infection with ah or ca virus conferred immunity to experimental challenge with homologous virus. These findings indicate that both ah and ca influenza A/Bethesda/85 (H3N2) reassortants should be suitable vaccine candidates for use in healthy infants and young children.

            Descriptors:  influenza prevention and control, influenza A virus avian immunology, human immunology, influenza vaccine immunology, antibodies, viral biosynthesis, child, preschool, cold, dose response relationship, immunologic, double blind method, enzyme linked immunosorbent assay, immunoglobulin G biosynthesis, infant, avian isolation and purification, human isolation and purification, randomized controlled trials, vaccines, attenuated immunology, vaccines, synthetic immunology.

Stephenson, I., K.G. Nicholson, J.M. Wood, M.C. Zambon, and J.M. Katz (2004). Confronting the avian influenza threat: vaccine development for a potential pandemic. Lancet Infectious Diseases 4(8): 499-509.  ISSN: 1473-3099.

            Abstract:  Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods. An emerging pandemic virus will create a surge in worldwide vaccine demand and new approaches in immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine antigen may be limited. The manufacture of vaccines from pathogenic avian influenza viruses by traditional methods is not feasible for safety reasons as well as technical issues. Strategies adopted to overcome these issues include the use of reverse genetic systems to generate reassortant strains, the use of baculovirus-expressed haemagglutinin or related non-pathogenic avian influenza strains, and the use of adjuvants to enhance immunogenicity. In clinical trials, conventional surface-antigen influenza virus vaccines produced from avian viruses have proved poorly immunogenic in immunologically naive populations. Adjuvanted or whole-virus preparations may improve immunogenicity and allow sparing of antigen.

            Descriptors:  disease outbreaks prevention and control, influenza immunology, influenza A virus, avian immunology, influenza vaccines immunology, avian influenza immunology, poultry diseases immunology, influenza prevention and control, influenza A virus, avian influenza genetics, influenza vaccines therapeutic use, avian influenza prevention and control, poultry, poultry diseases prevention and control, reassortant viruses immunology, vaccination, vaccines, attenuated immunology, attenuated therapeutic use.

Stephenson, I.N.K.G., R. Gluck, R. Mischler, R.W. Newman, A.M. Palache, N.Q. Verlander, F. Warburton, J.M. Wood, and M.C. Zambon (2003). Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9nN2) vaccine in healthy adults: phase I randomised trial. Lancet 362(9400): 1959-1966.  ISSN: 0099-5355.

            NAL Call Number:  448.8 L22

            Descriptors:  clinical immunology, humans, infection, vaccination, clinical techniques, immune response.

Stohr, K. (2005). Avian influenza and pandemics--research needs and opportunities. New England Journal of Medicine 352(4): 405-7.  ISSN: 1533-4406.

            NAL Call Number:  448.8 N442

            Descriptors:  disease outbreaks prevention and control, influenza transmission, influenza A virus, avian influenza classification, avian genetics, biomedical research, birds, disease transmission prevention and control, influenza epidemiology, influenza virology, avian influenza transmission, swine, zoonoses transmission.

Stohr, K. and M. Esveld (2004). Public health. Will vaccines be available for the next influenza pandemic? Science 306(5705): 2195-6.  ISSN: 1095-9203.

            NAL Call Number:  470 Sci2

            Descriptors:  disease outbreaks, influenza epidemiology, influenza prevention and control, influenza vaccines supply and distribution, clinical trials, drug industry, influenza virology, influenza A virus, avian immunology, avian pathogenicity, human immunology, influenza vaccines administration and dosage, influenza vaccines economics, international cooperation, population surveillance, public policy, World Health Organization.

Suarez, D.L., M.L. Perdue, N. Cox, T. Rowe, C. Bender, J. Huang, and D.E. Swayne (1998). Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong. Journal of Virology 72(8): 6678-88.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May 1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science 279:393-395, 1998). Gene sequences of this human isolate were compared to those of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in April 1997. Sequence comparisons of all eight RNA segments from the two viruses show greater than 99% sequence identity between them. However, neither isolate's gene sequence was closely (>95% sequence identity) related to any other gene sequences found in the GenBank database. Phylogenetic analysis demonstrated that the nucleotide sequences of at least four of the eight RNA segments clustered with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic analysis also included the sequences from an additional three human and two chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two closely related groups. However, no single amino acid change separated the chicken origin and human origin isolates, but they all contained multiple basic amino acids at the hemagglutinin cleavage site, which is associated with a highly pathogenic phenotype in poultry. In experimental intravenous inoculation studies with chickens, all seven viruses were highly pathogenic, killing most birds within 24 h. All infected chickens had virtually identical pathologic lesions, including moderate to severe diffuse edema and interstitial pneumonitis. Viral nucleoprotein was most frequently demonstrated in vascular endothelium, macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema and generalized cardiovascular collapse were the most likely pathogenic mechanisms responsible for illness and death. In summary, a small number of changes in hemagglutinin gene sequences defined two closely related subgroups, with both subgroups having human and chicken members, among the seven viruses examined from Hong Kong, and all seven viruses were highly pathogenic in chickens and caused similar lesions in experimental inoculations.

            Descriptors:  chickens virology, influenza virology, influenza A virus avian genetics, human genetics, amino acid sequence, cell line, chick embryo, dogs, hemagglutinin glycoproteins, influenza virus genetics, Hong Kong epidemiology, influenza epidemiology, avian classification, avian pathogenicity, human classification, human isolation and purification, human pathogenicity, molecular sequence data, phylogeny, virulence.

Suarez, D.L., P.R. Woolcock, A.J. Bermudez, and D.A. Senne (2002). Isolation from turkey breeder hens of a reassortant H1N2 influenza virus with swine, human, and avian lineage genes. Avian Diseases 46(1): 111-121.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Abstract:  Type A influenza viruses can infect a wide range of birds and mammals, but influenza in a particular species is usually considered to be species specific. However, infection of turkeys with swine H1N1 viruses has been documented on several occasions. This report documents the isolation of an H1N2 influenza virus from a turkey breeder flock with a sudden drop in egg production. Sequence analysis of the virus showed that it was a complex reassortant virus with a mix of swine-, human-, and avian-origin influenza genes. A swine influenza virus with a similar gene complement was recently reported from pigs in Indiana. Isolation and identification of the virus required the use of nonconventional diagnostic procedures. The virus was isolated in embryonated chicken eggs by the yolk sac route of inoculation rather than by the typical chorioallantoic sac route. Interpretation of hemagglutination-inhibition test results required the use of turkey rather than chicken red blood cells, and identification of the neuraminidase subtype required the use of alternative reference sera in the neuraminidase-inhibition test. This report provides additional evidence that influenza viruses can cross species and cause a disease outbreak, and diagnosticians must be aware that the variability of influenza viruses can complicate the isolation and characterization of new isolates.

            Descriptors:  infection, molecular genetics, veterinary medicine, hemagglutination inhibition test identification method, neuraminidase inhibition test identification method, sequence analysis molecular genetic method, yolk sac inoculation culture method, gene complement host specificity.

Subbarao, K. (2001). Influenza A infections: from chickens to humans. Clinical Microbiology Newsletter 23(2): 9-13.  ISSN: 0196-4399.

            Descriptors:  diagnosis, disease transmission, epidemiology, outbreaks, poultry, avian influenza virus, humans, China, Hong Kong.

Subbarao, K. and J. Katz (2000). Avian influenza viruses infecting humans. Cellular and Molecular Life Sciences CMLS 57(12): 1770-84.  ISSN: 1420-682X.

            NAL Call Number:  QH301.C45

            Abstract:  Avian species, particularly waterfowl, are the natural hosts of influenza A viruses. Influenza viruses bearing each of the 15 hemagglutinin and nine neuraminidase subtypes infect birds and serve as a reservoir from which influenza viruses or genes are introduced into the human population. Viruses with novel hemagglutinin genes derived from avian influenza viruses, with or without other accompanying avian influenza virus genes, have the potential for pandemic spread when the human population lacks protective immunity against the new hemagglutinin. Avian influenza viruses were thought to be limited in their ability to directly infect humans until 1997, when 18 human infections with avian influenza H5N1 viruses occurred in Hong Kong. In 1999, two human infections with avian influenza H9N2 viruses were also identified in Hong Kong. These events established that avian viruses could infect humans without acquiring human influenza genes by reassortment in an intermediate host and highlighted challenges associated with the detection of human immune responses to avian influenza viruses and the development of appropriate vaccines.

            Descriptors:  influenza virology, influenza A virus avian pathogenicity, antibodies, viral biosynthesis, birds, disease models, animal, disease outbreaks, fowl plague epidemiology, Hong Kong epidemiology, immunity, cellular, influenza epidemiology, influenza immunology, avian genetics, avian immunology, influenza vaccine isolation and purification, mammals, models, biological, phylogeny, species specificity, virulence.

Subbarao, K., A. Klimov, J. Katz, H. Regnery, W. Lim, H. Hall,  M. Perdue, D. Swayne, C. Bender, J. Huang, M. Hemphill, T. Rowe, M. Shaw, X. Xu, K. Fukuda, and N. Cox (1998). Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279(5349): 393-6.  ISSN: 0036-8075.

            NAL Call Number:  470 Sci2

            Abstract:  An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

            Descriptors:  hemagglutinin glycoproteins, influenza virus genetics, influenza virology, influenza A virus avian genetics, avian pathogenicity, amino acid sequence, cell line, chickens, child, preschool, disease outbreaks, fatal outcome, fowl plague virology, genes viral, hemagglutinin glycoproteins, influenza virus chemistry, Hong Kong epidemiology, influenza epidemiology, avian isolation and purification, molecular sequence data, neuraminidase genetics, phylogeny, virulence, virus replication.

Subbarao, K. and M.W. Shaw (2000). Molecular aspects of avian influenza (H5N1) viruses isolated from humans. Reviews in Medical Virology 10(5): 337-48.  ISSN: 1052-9276.

            Descriptors:  fowl plague transmission, influenza virology, influenza A virus avian genetics, avian isolation and purification, birds, fowl plague virology, genes viral, influenza diagnosis, avian classification, avian pathogenicity.

Subbarao, K., R.G. Webster, Y. Kawaoka, and B.R. Murphy (1995). Are there alternative avian influenza viruses for generation of stable attenuated avian-human influenza A reassortant viruses? Virus Research 39(2-3): 105-18.  ISSN: 0168-1702.

            NAL Call Number:  QR375.V6

            Abstract:  The present study evaluated gull influenza A viruses as donors of attenuating genes for the production of live, attenuated influenza A H1N1 and H3N2 avian-human (ah) reassortant viruses for use as vaccines to prevent disease due to influenza A viruses in humans. The previously evaluated duck influenza A viruses were abandoned as donors of attenuating avian influenza virus genes because clinical evaluation of H1N1 and H3N2 ah reassortant virus vaccines derived from duck viruses documented residual virulence of H1N1 reassortants for seronegative infants and young children. Gull influenza A viruses occupy an independent ecologic niche and are rarely isolated from species other than gulls. The possibility of using gull influenza A viruses as donors of internal gene segments in ah reassortant viruses was evaluated in the present study using three different gull viruses and three human influenza A viruses. Gull-human H3N2 reassortant influenza A viruses with the desired 6-2 genotype (six internal avian influenza virus genes and the two human influenza virus surface glycoprotein genes) were readily generated and were found to be attenuated for squirrel monkeys and chimpanzees. However, ah reassortant viruses with gull and human influenza A H1N1 genes were difficult to generate, and reassortants that had the desired genotype of six gull virus genes with human influenza A H1 and N1 genes were not isolated despite repeated attempts. The gull PB2, NP and NS genes were not present in any of the gull-human H1N1 reassortants generated. The under-representation of these three gene segments suggests that reassortants bearing one or more of these three gene segments might have reduced viability indicative of a functional incompatibility in their gene products. The difficulties encountered in the generation of a 6-2 gull-human H1N1 reassortant virus are sufficient to conclude that the gull influenza A viruses tested would not be useful as donors of sets of six internal genes to attenuate human influenza A viruses. This study also identifies influenza virus gene segments that appear to be incompatible for generation of reassortants. Elucidation of the molecular basis of this restriction may provide information on intergenic interactions involved in virion assembly or packaging.

            Descriptors:  influenza A virus avian genetics, human genetics, reassortant viruses genetics, cell line, chick embryo, chickens, dogs, genotype, Pan troglodytes, reassortant viruses isolation and purification, reassortant viruses physiology, reproducibility of results, saimiri, tissue culture, vaccines, attenuated genetics, vaccines, attenuated isolation and purification, viral vaccines genetics, viral vaccines isolation and purification, virus replication.

Suzuki, H. (2004). [Super pathogenic avian influenza]. [Zasshi] Journal. Nihon Naika Gakkai 93(11): 2323-7.  ISSN: 0021-5384.

            Descriptors:  chickens, influenza virology, avian influenza A virus pathogenicity, avian influenza virology, poultry diseases virology, zoonoses virology, acetamides therapeutic use, amantadine therapeutic use, antiviral agents therapeutic use, disease outbreaks, influenza epidemiology, influenza therapy, influenza transmission, influenza vaccines, avian influenza epidemiology, avian influenza transmission, neuraminidase antagonists and inhibitors, poultry diseases epidemiology, poultry diseases transmission, sialic acids therapeutic use, zoonoses epidemiology, zoonoses transmission.

Swayne, D.E. (2000). Understanding the ecology and epidemiology of avian influenza viruses: implications for zoonotic potential. In: C. Brown and C. Bolin (editors), Emerging Diseases of Animals, ASM Press: Washington, DC, p. 101-130. ISBN: 1555812015.

            NAL Call Number:  SF781.E53 2000

            Descriptors:  Aves, virus transmission, avian influenza viruses, ecology, epidemiology, zoonotic potential implications.

Syurin, V.N., N.G. Osidze, Z.Y. Chistova, and V. Rodin Yu (1972). [Epizootiological potential of avian influenza virus.]. Veterinariia (8): 41-43.

            NAL Call Number:  41.8 V6426

            Descriptors:  avian influenza virus, poultry.

Takada, A., N. Kuboki, K. Okazaki, A. Ninomiya, H. Tanaka, H. Ozaki, S. Itamura, H. Nishimura, M. Enami, M. Tashiro, K.F. Shortridge, and H. Kida (1999). Avirulent Avian influenza virus as a vaccine strain against a potential human pandemic. Journal of Virology 73(10): 8303-7.  ISSN: 0022-538X.

            NAL Call Number:  QR360.J6

            Abstract:  In the influenza H5N1 virus incident in Hong Kong in 1997, viruses that are closely related to H5N1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possibility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surrogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an avirulent recombinant H5N1 virus generated by reverse genetics, have been explored. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inhibiting and virus-neutralizing antibodies, while intranasal vaccination without adjuvant induced both mucosal and systemic antibody responses that protected the mice from lethal H5N1 virus challenge. Surveillance of birds and animals, particularly aquatic birds, for viruses to provide vaccine strains, especially surrogate viruses, for a future pandemic is stressed.

            Descriptors:  influenza immunology, influenza A virus avian immunology, influenza vaccine immunology, communicable disease control, disease outbreaks, influenza prevention and control, influenza vaccine administration and dosage, mice, vaccination.

Takahashi, T., Y. Suzuki, D. Nishinaka, N. Kawase, Y. Kobayashi, K.I. Hidari, D. Miyamoto, C.T. Guo, K.F. Shortridge, and T. Suzuki (2001). Duck and human pandemic influenza A viruses retain sialidase activity under low pH conditions. Journal of Biochemistry 130(2): 279-83.  ISSN: 0021-924X.

            NAL Call Number:  385 J822

            Abstract:  The majority of influenza A viruses isolated from wild birds, but not humans, can replicate in the duck intestinal tract. Here we demonstrate that all duck isolates tested universally retain sialidase activities under low pH conditions independent of their neuraminidase (NA) subtypes. In contrast, the sialidase activities of most isolates from humans and pigs practically disappear below pH 4.5, with the exception of four human pandemic viruses isolated in 1957 and 1968. Sequence comparisons among duck, human, and swine N2 NA subtypes indicate that amino acids at positions 153, 253, 307, 329, 344, 347, 356, 368, 390, and 431 may be associated with the low pH stability of duck and human pandemic N2 NAs. This finding suggests that the low pH stability of duck influenza A virus NA may be a critical factor for replication in the intestinal tract through the digestive tract of ducks, and that the properties of NAs are important for understanding the epidemiology of the influenza virus.

            Descriptors:  influenza virology, influenza A virus avian enzymology, human enzymology, neuraminidase metabolism, ducks, enzyme stability, hydrogen-ion concentration, influenza transmission, avian physiology, human physiology, porcine enzymology, phylogeny, sequence analysis, swine.

Tanaka, H., Park ChunHo, A. Ninomiya, H. Ozaki, A. Takada, T. Umemura, and H. Kida (2003). Neurotropism of the 1997 Hong Kong H5N1 influenza virus in mice. Veterinary Microbiology 95(1/2): 1-13.  ISSN: 0378-1135.

            NAL Call Number:  SF601.V44

            Descriptors:  disease transmission, encephalitis, experimental infection, pathogenesis, pathogenicity, zoonoses, avian influenza virus, influenza virus A, humans,  poultry, mice, China, Hong Kong.

Taubenberger, J.K., A.H. Reid, A.E. Krafft, K.E. Bijwaard, and T.G. Fanning (1997). Initial genetic characterization of the 1918 "Spanish" influenza virus. Science 275(5307): 1793-6.  ISSN: 0036-8075.

            NAL Call Number:  470 Sci2

            Abstract:  The "Spanish" influenza pandemic killed at least 20 million people in 1918-1919, making it the worst infectious pandemic in history. Understanding the origins of the 1918 virus and the basis for its exceptional virulence may aid in the prediction of future influenza pandemics. RNA from a victim of the 1918 pandemic was isolated from a formalin-fixed, paraffin-embedded, lung tissue sample. Nine fragments of viral RNA were sequenced from the coding regions of hemagglutinin, neuraminidase, nucleoprotein, matrix protein 1, and matrix protein 2. The sequences are consistent with a novel H1N1 influenza A virus that belongs to the subgroup of strains that infect humans and swine, not the avian subgroup.

            Descriptors:  genes viral, influenza virology, influenza A virus human genetics, porcine genetics, RNA viral genetics, algorithms, base sequence, hemagglutinin glycoproteins, influenza virus genetics, history of medicine, 20th century, influenza history, avian genetics, human classification, human pathogenicity, porcine classification, porcine pathogenicity, lung virology, molecular sequence data, neuraminidase genetics, nucleoproteins genetics, phylogeny, polymerase chain reaction, viral core proteins genetics, viral matrix proteins genetics, virulence.

Taubenberger, J.K. (2003 ). Fixed and frozen flu: The 1918 influenza and lessons for the future. Avian Diseases 47(Special Issue): 789-791.  ISSN: 0005-2086.

            NAL Call Number:  41.8 Av5

            Descriptors:  epidemiology, infection, Spanish influenza, epidemiology, infectious disease, respiratory system disease, viral disease, avian influenza, epidemiology, infectious disease, respiratory system disease, viral disease, 1918 Spanish influenza pandemic virulence.

Taylor, H.R. and A.J. Turner (1977). A case report of fowl plague keratoconjunctivitis. British Journal of Ophthalmology 61(2): 86-8.  ISSN: 0007-1161.

            Abstract:  A case of human fowl plague keratoconjunctivitis occurred after accidental laboratory exposure. The conjunctivitis was characterised by follicle formation and a mucopurulent discharge, and ran a self-limiting course over two weeks. The keratitis was of an unusual type and consisted of small intraepithelial opacities, which appeared after one we