1887

Abstract

Highly pathogenic H5N1 avian influenza virus has spread through at least 45 countries in three continents. Despite the ability to infect and cause severe disease in humans, the virus cannot transmit efficiently from human to human. The lack of efficient transmission indicates the incompletion of the adaptation of the avian virus to the new host species. The required mutations for the complete adaptation and the emergence of a potential pandemic virus are likely to originate and be selected within infected human tissues. Differential receptor preference plays an important role in the species-tropism of avian influenza. We have analysed quasispecies of sequences covering the receptor-binding domain of the haemagglutinin gene of H5N1 viruses derived from fatal human cases. We employed a likelihood ratio test to identify positive-selection sites within the quasispecies. Nine of seventeen positive-selection sites identified in our analyses were found to be located within or flanking the receptor-binding domain. Some of these mutations are known to alter receptor-binding specificity. This suggests that our approach could be used to screen for mutations with significant functional impact. Our data provide new candidate mutations for the viral adaptation to a human host, and a new approach to search for new genetic markers of potential pandemic viruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/002469-0
2008-08-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/8/1805.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/002469-0&mimeType=html&fmt=ahah

References

  1. Auewarakul, P., Suptawiwat, O., Kongchanagul, A., Sangma, C., Suzuki, Y., Ungchusak, K., Louisirirotchanakul, S., Lerdsamran, H., Pooruk, P. & other authors ( 2007; ). An avian influenza H5N1 virus that binds to a human-type receptor. J Virol 81, 9950–9955.[CrossRef]
    [Google Scholar]
  2. Eigen, M. ( 1996; ). On the nature of virus quasispecies. Trends Microbiol 4, 216–218.[CrossRef]
    [Google Scholar]
  3. Gambaryan, A., Tuzikov, A., Pazynina, G., Bovin, N., Balish, A. & Klimov, A. ( 2006; ). Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology 344, 432–438.[CrossRef]
    [Google Scholar]
  4. Ha, Y., Stevens, D. J., Skehel, J. J. & Wiley, D. C. ( 2001; ). X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proc Natl Acad Sci U S A 98, 11181–11186.[CrossRef]
    [Google Scholar]
  5. Kaverin, N. V., Rudneva, I. A., Ilyushina, N. A., Varich, N. L., Lipatov, A. S., Smirnov, Y. A., Govorkova, E. A., Gitelman, A. K., Lvov, D. K. & Webster, R. G. ( 2002; ). Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza virus and phenotypic variation of escape mutants. J Gen Virol 83, 2497–2505.
    [Google Scholar]
  6. Kaverin, N. V., Rudneva, I. A., Govorkova, E. A., Timofeeva, T. A., Shilov, A. A., Kochergin-Nikitsky, K. S., Krylov, P. S. & Webster, R. G. ( 2007; ). Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies. J Virol 81, 12911–12917.[CrossRef]
    [Google Scholar]
  7. Nielsen, R. & Yang, Z. ( 1998; ). Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148, 929–936.
    [Google Scholar]
  8. Rogers, G. N. & Paulson, J. C. ( 1983; ). Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127, 361–373.[CrossRef]
    [Google Scholar]
  9. Shinya, K., Hatta, M., Yamada, S., Takada, A., Watanabe, S., Halfmann, P., Horimoto, T., Neumann, G., Kim, J. H. & other authors ( 2005; ). Characterization of a human H5N1 influenza A virus isolated in 2003. J Virol 79, 9926–9932.[CrossRef]
    [Google Scholar]
  10. Skehel, J. J. & Wiley, D. C. ( 2000; ). Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69, 531–569.[CrossRef]
    [Google Scholar]
  11. Stevens, J., Blixt, O., Tumpey, T. M., Taubenberger, J. K., Paulson, J. C. & Wilson, I. A. ( 2006; ). Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312, 404–410.[CrossRef]
    [Google Scholar]
  12. Subbarao, K., Klimov, A., Katz, J., Regnery, H., Lim, W., Hall, H., Perdue, M., Swayne, D., Bender, C. & other authors ( 1998; ). Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279, 393–396.[CrossRef]
    [Google Scholar]
  13. Tran, T. H., Nguyen, T. L., Nguyen, T. D., Luong, T. S., Pham, P. M., Nguyen, V. C., Pham, T. S., Vo, C. D., Le, T. Q. & other authors ( 2004; ). Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 350, 1179–1188.[CrossRef]
    [Google Scholar]
  14. Uiprasertkul, M., Puthavathana, P., Sangsiriwut, K., Pooruk, P., Srisook, K., Peiris, M., Nicholls, J. M., Chokephaibulkit, K., Vanprapar, N. & Auewarakul, P. ( 2005; ). Influenza A H5N1 replication sites in humans. Emerg Infect Dis 11, 1036–1041.[CrossRef]
    [Google Scholar]
  15. Uiprasertkul, M., Kitphati, R., Puthavathana, P., Kriwong, R., Kongchanagul, A., Ungchusak, K., Angkasekwinai, S., Chokephaibulkit, K., Srisook, K. & other authors ( 2007; ). Apoptosis and pathogenesis of avian influenza A (H5N1) virus in humans. Emerg Infect Dis 13, 708–712.[CrossRef]
    [Google Scholar]
  16. Yamada, S., Suzuki, Y., Suzuki, T., Le, M. Q., Nidom, C. A., Sakai-Tagawa, Y., Muramoto, Y., Ito, M., Kiso, M. & other authors ( 2006; ). Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature 444, 378–382.[CrossRef]
    [Google Scholar]
  17. Yang, Z. ( 1997; ). paml: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 13, 555–556.
    [Google Scholar]
  18. Yang, Z. & Nielsen, R. ( 2000; ). Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. Mol Biol Evol 17, 32–43.[CrossRef]
    [Google Scholar]
  19. Yang, Z., Wong, W. S. & Nielsen, R. ( 2005; ). Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 22, 1107–1118.[CrossRef]
    [Google Scholar]
  20. Yao, L., Korteweg, C., Hsueh, W. & Gu, J. ( 2008; ). Avian influenza receptor expression in H5N1-infected and noninfected human tissues. FASEB J 22, 733–740.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.2008/002469-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/002469-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error