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MeSH Review

Influenza A Virus, H5N1 Subtype

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Disease relevance of Influenza A Virus, H5N1 Subtype

  • The hemagglutinin and neuraminidase genes of the new genotype were derived from Gs/Gd/96-like viruses and the nuclear protein gene descended from the 2001 genotype A H5N1 viruses, while the other inner genes originated from an unknown influenza virus [1].
  • In addition, we showed that M2 antisera were cross reactive with M2 peptides derived from a wide range of human influenza A strains, but they failed to react with M2 peptides of the pathogenic H5N1 virus (A/Hong Kong/97) [2].
  • The fear that avian influenza could be a precursor to the next pandemic is real and inevitable, given the extremely high case-fatality ratio among confirmed cases and that genetic sequencing of influenza A (H5N1) viruses from human cases in Thailand and Vietnam show resistance to the antiviral medication amantadine and rimantadine [3].

High impact information on Influenza A Virus, H5N1 Subtype

  • Our findings suggest that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier [4].
  • A human pandemic with H5N1 virus could potentially be catastrophic because most human populations have negligible antibody-mediated immunity to the H5 surface protein and this viral subtype is highly virulent [5].
  • 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 [6].
  • When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death [7].
  • Sequence analysis revealed that six genes (PB1, PA, HA, NA, M, and NS) of this virus showed >97% nucleotide identity with their counterparts from recent H5N1 viruses, but that the remaining two genes (PB2 and NP) were derived from other unknown viruses [8].

Chemical compound and disease context of Influenza A Virus, H5N1 Subtype

  • Amino acid residues at the receptor-binding site of the five human viruses were similar to those of the chicken virus and other H5N1 viruses from Hong Kong. The presence of amantadine resistance in the Thailand viruses isolated during this outbreak was suggested by a fixed mutation in M2 and confirmed by a phenotypic assay [9].
  • Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2 [10].
  • When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control [11].
  • However, mutations that can convert avian H2 and H3 HAs to human receptor specificity, when inserted onto the Viet04 H5 HA framework, permitted binding to a natural human alpha2-6 glycan, which suggests a path for this H5N1 virus to gain a foothold in the human population [12].

Gene context of Influenza A Virus, H5N1 Subtype

  • Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus [13].
  • Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong [14].
  • 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 [15].


  1. New genotype of avian influenza H5N1 viruses isolated from tree sparrows in China. Kou, Z., Lei, F.M., Yu, J., Fan, Z.J., Yin, Z.H., Jia, C.X., Xiong, K.J., Sun, Y.H., Zhang, X.W., Wu, X.M., Gao, X.B., Li, T.X. J. Virol. (2005) [Pubmed]
  2. Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Fan, J., Liang, X., Horton, M.S., Perry, H.C., Citron, M.P., Heidecker, G.J., Fu, T.M., Joyce, J., Przysiecki, C.T., Keller, P.M., Garsky, V.M., Ionescu, R., Rippeon, Y., Shi, L., Chastain, M.A., Condra, J.H., Davies, M.E., Liao, J., Emini, E.A., Shiver, J.W. Vaccine (2004) [Pubmed]
  3. Influenza: the next pandemic?: A review. Adungo, F.O., Adungo, N.I., Bedno, S., Yingst, S.L. East African medical journal. (2005) [Pubmed]
  4. The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. Salomon, R., Franks, J., Govorkova, E.A., Ilyushina, N.A., Yen, H.L., Hulse-Post, D.J., Humberd, J., Trichet, M., Rehg, J.E., Webby, R.J., Webster, R.G., Hoffmann, E. J. Exp. Med. (2006) [Pubmed]
  5. Avian flu to human influenza. Lewis, D.B. Annu. Rev. Med. (2006) [Pubmed]
  6. DNA vaccine encoding hemagglutinin provides protective immunity against H5N1 influenza virus infection in mice. Kodihalli, S., Goto, H., Kobasa, D.L., Krauss, S., Kawaoka, Y., Webster, R.G. J. Virol. (1999) [Pubmed]
  7. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Govorkova, E.A., Leneva, I.A., Goloubeva, O.G., Bush, K., Webster, R.G. Antimicrob. Agents Chemother. (2001) [Pubmed]
  8. Isolation of a genotypically unique H5N1 influenza virus from duck meat imported into Japan from China. Mase, M., Eto, M., Tanimura, N., Imai, K., Tsukamoto, K., Horimoto, T., Kawaoka, Y., Yamaguchi, S. Virology (2005) [Pubmed]
  9. Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand. Puthavathana, P., Auewarakul, P., Charoenying, P.C., Sangsiriwut, K., Pooruk, P., Boonnak, K., Khanyok, R., Thawachsupa, P., Kijphati, R., Sawanpanyalert, P. J. Gen. Virol. (2005) [Pubmed]
  10. Evolutionary characterization of the six internal genes of H5N1 human influenza A virus. Hiromoto, Y., Yamazaki, Y., Fukushima, T., Saito, T., Lindstrom, S.E., Omoe, K., Nerome, R., Lim, W., Sugita, S., Nerome, K. J. Gen. Virol. (2000) [Pubmed]
  11. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Leneva, I.A., Roberts, N., Govorkova, E.A., Goloubeva, O.G., Webster, R.G. Antiviral Res. (2000) [Pubmed]
  12. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Stevens, J., Blixt, O., Tumpey, T.M., Taubenberger, J.K., Paulson, J.C., Wilson, I.A. Science (2006) [Pubmed]
  13. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Chan, M.C., Cheung, C.Y., Chui, W.H., Tsao, S.W., Nicholls, J.M., Chan, Y.O., Chan, R.W., Long, H.T., Poon, L.L., Guan, Y., Peiris, J.S. Respir. Res. (2005) [Pubmed]
  14. Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Xu, X., Subbarao, n.u.l.l., Cox, N.J., Guo, Y. Virology (1999) [Pubmed]
  15. Characterization of the influenza A virus gene pool in avian species in southern China: was H6N1 a derivative or a precursor of H5N1? Hoffmann, E., Stech, J., Leneva, I., Krauss, S., Scholtissek, C., Chin, P.S., Peiris, M., Shortridge, K.F., Webster, R.G. J. Virol. (2000) [Pubmed]
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