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.