Vietnam is one of the countries most affected by highly pathogenic H5N1 influenza A viruses. To evaluate the potential pathogenicity in mammals of H5N1 viruses isolated from humans in Vietnam, we determined the sequences of all eight genes of 22 human isolates collected between 2003 and 2008 and compared their virulence in mice. The isolates were classified into clade 1 and clade 2.3.4 and differed in pathogenicity for mice. Whilst lysine at position 627 of PB2 (PB2-627K) is a critical virulence determinant for clade 2.3.4 viruses, asparagine at position 701 of PB2 and other unknown virulence determinants appear to be involved in the high pathogenicity of clade 1 viruses, warranting further studies to determine the factors responsible for the high virulence of H5N1 viruses in mammals.


Article metrics loading...

Loading full text...

Full text loading...



  1. Conenello, G. M., Zamarin, D., Perrone, L. A., Tumpey, T. & Palese, P.(2007). A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog 3, 1414–1421. [Google Scholar]
  2. Dinh, P. N., Long, H. T., Tien, N. T., Hien, N. T., Mai, L. T. Q., Phong, L. H., Tuan, L. V., Tan, H. V., Nguyen, N. B. & other authors(2006). Risk factors for human infection with avian influenza A H5N1, Vietnam, 2004. Emerg Infect Dis 12, 1841–1847.[CrossRef] [Google Scholar]
  3. 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]
  4. 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]
  5. Hatakeyama, S., Sakai-Tagawa, Y., Kiso, M., Goto, H., Kawakami, C., Mitamura, K., Sugaya, N., Suzuki, Y. & Kawaoka, Y.(2005). Enhanced expression of an α2,6-linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor. J Clin Microbiol 43, 4139–4146.[CrossRef] [Google Scholar]
  6. Hatta, M., Gao, P., Halfmann, P. & Kawaoka, Y.(2001). Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293, 1840–1842.[CrossRef] [Google Scholar]
  7. Hatta, M., Hatta, Y., Kim, J. H., Watanabe, S., Shinya, K., Nguyen, T., Lien, P. S., Le, Q. M. & Kawaoka, Y.(2007). Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice. PLoS Pathog 3, 1374–1379. [Google Scholar]
  8. Jackson, D., Hossain, M. J., Hickman, D., Perez, D. R. & Lamb, R. A.(2008). A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. Proc Natl Acad Sci U S A 105, 4381–4386.[CrossRef] [Google Scholar]
  9. 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]
  10. Maines, T. R., Lu, X. H., Erb, S. M., Edwards, L., Guarner, J., Greer, P. W., Nguyen, D. C., Szretter, K. J., Chen, L. M. & 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]
  11. 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]
  12. OIE(2010). Update on highly pathogenic avian influenza in animals (type H5 and H7). Accessed 1 March 2010. http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI-Asia.htm.
  13. Ozawa, M., Fujii, K., Muramoto, Y., Yamada, S., Yamayoshi, S., Takada, A., Goto, H., Horimoto, T. & Kawaoka, Y.(2007). Contributions of two nuclear localization signals of influenza A virus nucleoprotein to viral replication. J Virol 81, 30–41.[CrossRef] [Google Scholar]
  14. Reed, L. J. & Muench, H.(1938). A simple method of estimating fifty per cent endpoints. Am J Hyg 27, 493–497. [Google Scholar]
  15. Seo, S. H., Hoffmann, E. & Webster, R. G.(2002). Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8, 950–954.[CrossRef] [Google Scholar]
  16. 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]
  17. Wan, X. F., Nguyen, T., Davis, C. T., Smith, C. B., Zhao, Z. M., Carrel, M., Inui, K., Do, H. T., Mai, D. T. & other authors(2008). Evolution of highly pathogenic H5N1 avian influenza viruses in Vietnam between 2001 and 2007. PLoS One 3, e3462.[CrossRef] [Google Scholar]
  18. WHO(2008). Towards a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 14, e1. [Google Scholar]
  19. WHO(2010a). Antigenic and genetic characteristics of influenza A(H5N1) and influenza A(H9N2) viruses and candidate vaccine viruses developed for potential use in human vaccines. Accessed 1 March 2010. http://www.who.int/csr/disease/avian_influenza/guidelines/h5n1virus/en/index.html.
  20. WHO(2010b). Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Accessed 11 June 2010. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_06_08/en/index.html.

Data & Media loading...


vol. , part 10, pp. 2485–2490

Map of the provinces of northern Vietnam.

Phylogenetic relationships of the PB2, PB1, PA, NP, NA, M and NS genes of H5N1 influenza viruses isolated from patients in Vietnam.

Polymerase activity of UT3040 and UT3040II.

Amino acid differences between UT3040 and UT3040II viruses

[ Single PDF file] (4 MB)


Most cited this month Most Cited RSS feed

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