Protein & Cell

, Volume 4, Issue 11, pp 846–853 | Cite as

Origin and molecular characterization of the human-infecting H6N1 influenza virus in Taiwan

  • Weifeng Shi
  • Yi Shi
  • Ying Wu
  • Di Liu
  • George F. Gao
Research Article Protein & Cell

Abstract

In June 2013, the first human H6N1 influenza virus infection was confirmed in Taiwan. However, the origin and molecular characterization of this virus, A/Taiwan/2/2013 (H6N1), have not been well studied thus far. In the present report, we performed phylogenetic and coalescent analyses of this virus and compared its molecular profile/characteristics with other closely related strains. Molecular characterization of H6N1 revealed that it is a typical avian influenza virus of low pathogenicity, which might not replicate and propagate well in the upper airway in mammals. Phylogenetic analysis revealed that the virus clusters with A/chicken/Taiwan/A2837/2013 (H6N1) in seven genes, except PB1. For the PB1 gene, A/Taiwan/2/2013 was clustered with a different H6N1 lineage from A/chicken/Taiwan/ A2837/2013. Although a previous study demonstrated that the PB2, PA, and M genes of A/Taiwan/2/2013 might be derived from the H5N2 viruses, coalescent analyses revealed that these H5N2 viruses were derived from more recent strains than that of the ancestor of A/Taiwan/2/2013. Therefore, we propose that A/Taiwan/2/2013 is a reassortant from different H6N1 lineages circulating in chickens in Taiwan. Furthermore, compared to avian isolates, a single P186L (H3 numbering) substitution in the hemagglutinin H6 of the human isolate might increase the mammalian receptor binding and, hence, this strain’s pathogenicity in humans. Overall, human infection with this virus seems an accidental event and is unlikely to cause an influenza pandemic. However, its co-circulation and potential reassortment with other influenza subtypes are still worthy of attention.

Keywords

molecular characterization phylogenetic analysis coalescent analysis H6N1 influenza virus Taiwan 

References

  1. Beare, A.S., and Webster, R.G. (1991). Replication of avian influenza viruses in humans. Arch Virol 119, 37–42.CrossRefGoogle Scholar
  2. Chen, W., Calvo, P.A., Malide, D., Gibbs, J., Schubert, U., Bacik, I., Basta, S., O’Neill, R., Schickli, J., Palese, P., et al. (2001). A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7, 1306–1312.CrossRefGoogle Scholar
  3. Cheung, C.L., Vijaykrishna, D., Smith, G.J., Fan, X.H., Zhang, J.X., Bahl, J., Duan, L., Huang, K., Tai, H., Wang, J., et al. (2007). Establishment of influenza A virus (H6N1) in minor poultry species in southern China. J Virol 81, 10402–10412.CrossRefGoogle Scholar
  4. Drummond, A.J., and Rambaut, A. (2007). BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7, 214.CrossRefGoogle Scholar
  5. Edgar, R.C. (2004). Muscle: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32, 1792–1797.CrossRefGoogle Scholar
  6. Ha, Y., Stevens, D.J., Skehel, J.J., and 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.CrossRefGoogle Scholar
  7. Hatta, M., Gao, P., Halfmann, P., and Kawaoka, Y. (2001).Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293, 1840–1842.CrossRefGoogle Scholar
  8. Hoffmann, E., Stech, J., Leneva, I., Krauss, S., Scholtissek, C., Chin, P.S., Peiris, M., Shortridge, K.F., and Webster, R.G. (2000). Characterization of the influenza A virus gene pool in avian species in southern China: was H6N1 a derivative or a precursor of H5N1?. J Virol 74, 6309–6315.CrossRefGoogle Scholar
  9. Holsinger, L., Nichani, D., Pinto, L., and Lamb, R. (1994). Influenza A virus M2 ion channel protein: a structure-function analysis. J Virol 68, 1551–1563.Google Scholar
  10. Kiso, M., Ozawa, M., Le, M.T., Imai, H., Takahashi, K., Kakugawa, S., Noda, T., Horimoto, T., and Kawaoka, Y. (2011). Effect of an asparagine-to-serine mutation at position 294 in neuraminidase on the pathogenicity of highly pathogenic H5N1 influenza A virus. J Virol 85, 4667–4672.CrossRefGoogle Scholar
  11. Labadie, K., Dos Santos Afonso, E., Rameix-Welti, M.A., van der Werf, S., Naffakh, N. (2007). Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells. Virology 362, 271–282.CrossRefGoogle Scholar
  12. Lee, M.S., Chang, P.C., Shien, J.H., Cheng, M.C., Chen, C.L., and Shieh, H.K. (2006). Genetic and pathogenic characterization of H6N1 avian influenza viruses isolated in Taiwan between 1972 and 2005. Avian Dis 50, 561–571.CrossRefGoogle Scholar
  13. Liu, D., Shi, W., Shi, Y., Wang, D., Xiao, H., Li, W., Bi, Y., Wu, Y., Li, X., Yan, J., et al. (2013). Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. Lancet 381, 1926–1932.CrossRefGoogle Scholar
  14. Massin, P., van der Werf, S., and Naffakh, N. (2001). Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J Virol 75, 5398–5404.CrossRefGoogle Scholar
  15. Matrosovich, M., Zhou, N., Kawaoka, Y., and Webster, R.G. (1999). The surface glycoproteins of H5 influenza viruses isolated from humans chickens and wild aquatic birds have distinguishable properties. J Virol 73, 1146–1155.Google Scholar
  16. McAuley, J.L., Hornung, F., Boyd, K.L., Smith, A.M., McKeon, R., Bennink, J., Yewdell, J.W., and McCullers, J.A. (2007). Expression of the 1918 influenza A virus PB1-F2 enchances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2, 240–249.CrossRefGoogle Scholar
  17. Meunier, I., and von Messling, V. (2012). PB1-F2 modulates early host responses but does not affect the pathogenesis of H1N1 seasonal influenza virus. J Virol 86, 4271–4278.CrossRefGoogle Scholar
  18. Morens, D.M., Taubenberger, J.K., and Fauci, A.S. (2013). Pandemic influenza viruses—hoping for the road not taken. N Engl J Med 368, 2345–2348.CrossRefGoogle Scholar
  19. Myers, K.P., Setterquist, S.F., Capuano, A.W., and Gray, G.C. (2007). Infection due to 3 avian influenza subtypes in United States veterinarians. Clin Infect Dis 45, 4–9.CrossRefGoogle Scholar
  20. Pinto, L., Holsinger, L., and Lamb, R. (1992). Influenza virus M2 protein has ion channel activity. Cell 69, 517–528.CrossRefGoogle Scholar
  21. Senne, D.A. (2003). Avian influenza in the Western Hemisphere including the Pacific Islands and Australia. Avian Dis 47, 798–805.CrossRefGoogle Scholar
  22. Shi, Y., Zhang, W., Wang, F., Qi, J., Wu, Y., Song, H., Gao, F., Bi, Y., Zhang, Y., Fan, Z., et al. (2013). Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses. Science. (In Press).Google Scholar
  23. Shortridge, K.F. (1992). Pandemic influenza: a zoonosis?. Semin Respir Infect 7, 11–25.Google Scholar
  24. Stamatakis, A. (2006). RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22, 2688–2690.CrossRefGoogle Scholar
  25. Xiong, X., Martin, S.R., Haire, L.F., Wharton, S.A., Daniels, R.S., Bennett, M.S., McCauley, J.W., Collins, P.J., Walker, P.A., Skehel, J.J., et al. (2013). Receptor binding by an H7N9 influenza virus from human. Nature 499, 496–499.CrossRefGoogle Scholar
  26. Yuan, J., Zhang, L., Kan, X., Jiang, L., Yang, J., Guo, Z., and Ren, Q. (2013). Origin and molecular characteristics of a novel 2013 avian influenza A H6N1 virus causing human infection in Taiwan. Clin Infect Dis. (In Press).Google Scholar
  27. Zamarin, D., Ortigoza, M.B., and Palese, P. (2006). Influenza A virus PB1-F2 protein contributes to viral pathogenenesis in mice. J Virol 80, 7976–7983.CrossRefGoogle Scholar
  28. Zell, R., Krumbholz, A., Eitnerm A., Krieg, R., Halbhuber, K.J., and Wutzler, P. (2007). Prevalence of PB1-F2 of influenza A viruses. J Gen Virol 88, 536–546.CrossRefGoogle Scholar
  29. Zhang, W., Shi, Y., Lu, X., Shu, Y., Qi, J., and Gao, G.F. (2013). An airborne transmissible avian influenza H5 hemagglutinin seen at the atomic level. Science 340, 1463–1467.CrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Weifeng Shi
    • 1
  • Yi Shi
    • 2
    • 3
  • Ying Wu
    • 2
  • Di Liu
    • 2
    • 4
  • George F. Gao
    • 2
    • 3
    • 5
  1. 1.School of Medical SciencesTaishan Medical CollegeTaianChina
  2. 2.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  3. 3.Beijing Institutes of Life SciencesChinese Academy of SciencesBeijingChina
  4. 4.Network Information Center, Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  5. 5.Office of Director-GeneralChinese Center for Disease Control and Prevention (China CDC)BeijingChina

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