1887

Abstract

Wild waterfowl are a reservoir for influenza A viruses, which can be transmitted from these birds to other animal species. Occasionally, influenza A viruses are transmitted to other animal species from animals other than wild waterfowl, e.g. an equine influenza virus has been transmitted to dogs and caused outbreaks. To understand the molecular mechanism by which influenza A viruses adapt to a new animal species, the molecular changes involved in the adaptation of an H7N7 equine influenza A virus were studied in mice. Mutations in the mouse-adapted virus mapped to one amino acid change in the PA protein, one in PB2 and two in PB1. Of these mutations, the Glu-to-Lys substitution at position 627 of PB2 (PB2-E627K) increased virulence appreciably. To understand the mechanism of this increased virulence, a recombinant virus expressing a reporter green fluorescent protein was constructed, thus enabling the effect of this mutation on viral protein expression to be tested in the context of virus replication . It was found that the PB2-E627K substitution in this equine virus contributed to increased viral protein expression and virus replication in mouse cells and enhanced brain invasiveness in mice. These results demonstrate that the importance of the PB2-E627K substitution for mouse adaptation, which was identified previously in human H5N1 isolates, extends to equine influenza A virus.

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2007-02-01
2024-10-03
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References

  1. Brown E. G., Liu H., Kit L. C., Baird S., Nesrallah M. 2001; Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: identification of functional themes. Proc Natl Acad Sci U S A 98:6883–6888 [CrossRef]
    [Google Scholar]
  2. Chen H., Smith G. J., Zhang S. Y., Qin K., Wang J., Li K. S., Webster R. G., Peiris J. S., Guan Y. 2005; Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature 436:191–192 [CrossRef]
    [Google Scholar]
  3. Chen H., Li Y., Li Z., Shi J., Shinya K., Deng G., Qi Q., Tian G., Fan S. other authors 2006; Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. J Virol 80:5976–5983 [CrossRef]
    [Google Scholar]
  4. Crawford P. C., Dubovi E. J., Castleman W. L., Stephenson I., Gibbs E. P., Chen L., Smith C., Hill R. C., Ferro P. other authors 2005; Transmission of equine influenza virus to dogs. Science 310:482–485 [CrossRef]
    [Google Scholar]
  5. de Jong M. D., Bach V. C., Phan T. Q., Vo M. H., Tran T. T., Nguyen B. H., Beld M., Le T. P., Truong H. K. other authors 2005; Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med 352:686–691 [CrossRef]
    [Google Scholar]
  6. Fouchier R. A., Schneeberger P. M., Rozendaal F. W., Broekman J. M., Kemink S. A., Munster V., Kuiken T., Rimmelzwaan G. F., Schutten M. other authors 2004; Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A 101:1356–1361 [CrossRef]
    [Google Scholar]
  7. Fujii Y., Goto H., Watanabe T., Yoshida T., Kawaoka Y. 2003; Selective incorporation of influenza virus RNA segments into virions. Proc Natl Acad Sci U S A 100:2002–2007 [CrossRef]
    [Google Scholar]
  8. Gabriel G., Dauber B., Wolff T., Planz O., Klenk H. D., Stech J. 2005; The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci U S A 102:18590–18595 [CrossRef]
    [Google Scholar]
  9. Gao P., Watanabe S., Ito T., Goto H., Wells K., McGregor M., Cooley A. J., Kawaoka Y. 1999; Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. J Virol 73:3184–3189
    [Google Scholar]
  10. Govorkova E. A., Rehg J. E., Krauss S., Yen H. L., Guan Y., Peiris M., Nguyen T. D., Hanh T. H., Puthavathana P. other authors 2005; Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 79:2191–2198 [CrossRef]
    [Google Scholar]
  11. Hatta M., Gao G., Halfmann P., Kawaoka Y. 2001; Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293:1840–1842 [CrossRef]
    [Google Scholar]
  12. Hirst M., Astell C. R., Griffith M., Coughlin S. M., Moksa M., Zeng T., Smailus D. E., Holt R. A., Jones S. other authors 2004; Novel avian influenza H7N3 strain outbreak, British Columbia. Emerg Infect Dis 10:2192–2195 [CrossRef]
    [Google Scholar]
  13. Katz J. M., Lu X., Tumpey T. M., Smith C. B., Shaw M. W., Subbarao K. 2000; Molecular correlates of influenza A H5N1 virus pathogenesis in mice. J Virol 74:10807–10810 [CrossRef]
    [Google Scholar]
  14. Kawaoka Y. 1991; Equine H7N7 influenza A viruses are highly pathogenic in mice without adaptation: potential use as an animal model. J Virol 65:3891–3894
    [Google Scholar]
  15. Li Z., Chen H., Jiao P., Deng G., Tian G., Li Y., Hoffmann E., Webster R. G., Matsuoka Y., Yu K. 2005; Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 79:12058–12064 [CrossRef]
    [Google Scholar]
  16. Lipatov A. S., Krauss S., Guan Y., Peiris M., Rehg J. E., Perez D. R., Webster R. G. 2003; Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J Virol 77:3816–3823 [CrossRef]
    [Google Scholar]
  17. Liu J., Xiao H., Lei F., Zhu Q., Qin K., Zhang X. W., Zhang X. L., Zhao D., Wang G. other authors 2005; Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 309:1206 [CrossRef]
    [Google Scholar]
  18. Maines T. R., Lu X. H., Erb S. M., Zhu Q., Qin K., Zhang X. W., Zhang X. L., Zhao D., Wang G. other authors 2005; Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol 79:11788–11800 [CrossRef]
    [Google Scholar]
  19. Mase M., Eto M., Tanimura N., Imai K., Tsukamoto K., Horimoto T., Kawaoka Y., Yamaguchi S. 2005; Isolation of a genotypically unique H5N1 influenza virus from duck meat imported into Japan from China. Virology 339:101–109 [CrossRef]
    [Google Scholar]
  20. Naffakh N., Massin P., Escriou N., Crescenzo-Chaigne B., Van der Werf S. 2000; Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses. J Gen Virol 81:1283–1291
    [Google Scholar]
  21. Neumann G., Watanabe T., Ito H., Watanabe S., Goto H., Gao P., Hughes M., Perez D. R., Donis R. other authors 1999; Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A 96:9345–9350 [CrossRef]
    [Google Scholar]
  22. Rowe T., Cho D. S., Bright R. A., Zitzow L. A., Katz J. M. 2003; Neurological manifestations of avian influenza viruses in mammals. Avian Dis 47:1122–1126 [CrossRef]
    [Google Scholar]
  23. Salomon R., Franks J., Govorkova E. A., Ilyushina N. A., Yen H. L., Hulse-Post D. J., Humberd J., Trichet M., Rehg J. E. other authors 2006; The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 203:689–697 [CrossRef]
    [Google Scholar]
  24. Smith G. J., Naipospos T. S., Nguyen T. D., de Jong M. D., Vijaykrishna D., Usman T. B., Hassan S. S., Nguyen T. V., Dao T. V. other authors 2006; Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam. Virology 350:258–268 [CrossRef]
    [Google Scholar]
  25. Subbarao E. K., London W., Murphy B. R. 1993; A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 67:1761–1764
    [Google Scholar]
  26. Watanabe T., Watanabe S., Noda T., Fujii Y., Kawaoka Y. 2003; Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes. J Virol 77:10575–10583 [CrossRef]
    [Google Scholar]
  27. Webster R. G., Bean W. J., Gorman O. T., Chambers T. M., Kawaoka Y. 1992; Evolution and ecology of influenza A viruses. Microbiol Rev 56:152–179
    [Google Scholar]
  28. Zitzow L. A., Rowe T., Morken T., Shieh W. J., Zaki S., Katz J. M. 2002; Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 76:4420–4429 [CrossRef]
    [Google Scholar]
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