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Abstract

Recent large-scale sequence analyses revealed ‘signature’ amino acids at specific positions in viral proteins that distinguish human influenza viruses from avian viruses. To determine the role of these host lineage-specific amino acids in the pathogenicity of H5N1 avian influenza viruses, we generated mutant viruses possessing signature amino acids in the PB2, PA and NP proteins of human influenza isolates (‘human-like amino acids’) in the genetic background of an avian H5N1 virus, and tested their pathogenicity in mice. We found that some of these mutants exhibited enhanced pathogenicity in mice, suggesting the involvement of these host lineage-specific amino acids in the pathogenicity of H5N1 avian influenza viruses in mammals.

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2010-05-01
2024-03-29
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References

  1. Chen, G. W., Chang, S. C., Mok, C. K., Lo, Y. L., Kung, Y. N., Huang, J. H., Shih, Y. H., Wang, J. Y., Chiang, C. & other authors(2006). Genomic signatures of human versus avian influenza A viruses. Emerg Infect Dis 12, 1353–1360.[CrossRef] [Google Scholar]
  2. Cooper, L., Olsen, C., Xu, K., Klimov, A., Cox, N. & Subbarao, K.(1999). Molecular characterization of human influenza A viruses bearing swine-like hemagglutinin genes. In Abstracts from the Virus Evolution Workshop, Ardmore, OK, USA, 21–24 October 1999. http://www.noble.org/VirusEvolution/abstracts/Cooperpost.htm.
  3. Dawood, F. S., Jain, S., Finelli, L., Shaw, M. W., Lindstrom, S., Garten, R. J., Gubareva, L. V., Xu, X., Bridges, C. B. & Uyeki, T. M.(2009). Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360, 2605–2615.[CrossRef] [Google Scholar]
  4. Deng, T., Sharps, J. L. & Brownlee, G. G.(2006). Role of the influenza virus heterotrimeric RNA polymerase complex in the initiation of replication. J Gen Virol 87, 3373–3377.[CrossRef] [Google Scholar]
  5. Dias, A., Bouvier, D., Crepin, T., McCarthy, A. A., Hart, D. J., Baudin, F., Cusack, S. & Ruigrok, R. W.(2009). The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458, 914–918.[CrossRef] [Google Scholar]
  6. Finkelstein, D. B., Mukatira, S., Mehta, P. K., Obenauer, J. C., Su, X., Webster, R. G. & Naeve, C. W.(2007). Persistent host markers in pandemic and H5N1 influenza viruses. J Virol 81, 10292–10299.[CrossRef] [Google Scholar]
  7. Fornek, J. L., Gillim-Ross, L., Santos, C., Carter, V., Ward, J. M., Cheng, L. I., Proll, S., Katze, M. G. & Subbarao, K.(2009). A single amino acid substitution in a polymerase protein of an H5N1 influenza virus is associated with systemic infection and impaired T cell activation in mice. J Virol 83, 11102–11115.[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. Gregory, V., Lim, W., Cameron, K., Bennett, M., Marozin, S., Klimov, A., Hall, H., Cox, N., Hay, A. & Lin, Y. P.(2001). Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs. J Gen Virol 82, 1397–1406. [Google Scholar]
  10. Harvey, R., Martin, A. C., Zambon, M. & Barclay, W. S.(2004). Restrictions to the adaptation of influenza A virus H5 hemagglutinin to the human host. J Virol 78, 502–507.[CrossRef] [Google Scholar]
  11. 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]
  12. 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]
  13. Itoh, Y., Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y., Tamura, D., Sakai-Tagawa, Y. & other authors(2009).In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460, 1021–1025. [Google Scholar]
  14. Kashiwagi, T., Leung, B. W., Deng, T., Chen, H. & Brownlee, G. G.(2009). The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PLoS One 4, e5473[CrossRef] [Google Scholar]
  15. Klumpp, K., Ruigrok, R. W. & Baudin, F.(1997). Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure. EMBO J 16, 1248–1257.[CrossRef] [Google Scholar]
  16. 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]
  17. Macken, C., Lu, H., Goodman, J. & Boykin, L.(2001). The value of a database in surveillance and vaccine selection. In Options for the Control of Influenza IV, pp. 103–106. Edited by A. D. M. E. Osterhaus, N. Cox & A. W. Hampson. Amsterdam: Elsevier.
  18. 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]
  19. Maines, T. R., Chen, L. M., Matsuoka, Y., Chen, H., Rowe, T., Ortin, J., Falcon, A., Nguyen, T. H., Mai, L. Q. & other authors(2006). Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci U S A 103, 12121–12126.[CrossRef] [Google Scholar]
  20. Matrosovich, M. N., Matrosovich, T. Y., Gray, T., Roberts, N. A. & Klenk, H. D.(2004). Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol 78, 12665–12667.[CrossRef] [Google Scholar]
  21. Munster, V. J., de Wit, E., van den Brand, J. M., Herfst, S., Schrauwen, E. J., Bestebroer, T. M., van de Vijver, D., Boucher, C. A., Koopmans, M. & other authors(2009). Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 325, 481–483. [Google Scholar]
  22. 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]
  23. Olsen, C. W.(2002). The emergence of novel swine influenza viruses in North America. Virus Res 85, 199–210.[CrossRef] [Google Scholar]
  24. Scholtissek, C., Burger, H., Kistner, O. & Shortridge, K. F.(1985). The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses. Virology 147, 287–294.[CrossRef] [Google Scholar]
  25. Scull, M. A., Gillim-Ross, L., Santos, C., Roberts, K. L., Bordonali, E., Subbarao, K., Barclay, W. S. & Pickles, R. J.(2009). Avian influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways. PLoS Pathog 5, e1000424[CrossRef] [Google Scholar]
  26. Shaw, M., Cooper, L., Xu, X., Thompson, W., Krauss, S., Guan, Y., Zhou, N., Klimov, A., Cox, N. & other authors(2002). Molecular changes associated with the transmission of avian influenza A H5N1 and H9N2 viruses to humans. J Med Virol 66, 107–114.[CrossRef] [Google Scholar]
  27. Shinya, K., Hamm, S., Hatta, M., Ito, H., Ito, T. & Kawaoka, Y.(2004). PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology 320, 258–266.[CrossRef] [Google Scholar]
  28. Sorrell, E. M., Wan, H., Araya, Y., Song, H. & Perez, D. R.(2009). Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc Natl Acad Sci U S A 106, 7565–7570.[CrossRef] [Google Scholar]
  29. Steel, J., Lowen, A. C., Mubareka, S. & Palese, P.(2009). Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog 5, e1000252[CrossRef] [Google Scholar]
  30. Taubenberger, J. K., Reid, A. H., Krafft, A. E., Bijwaard, K. E. & Fanning, T. G.(1997). Initial genetic characterization of the 1918 “Spanish” influenza virus. Science 275, 1793–1796.[CrossRef] [Google Scholar]
  31. Taubenberger, J. K., Reid, A. H., Lourens, R. M., Wang, R., Jin, G. & Fanning, T. G.(2005). Characterization of the 1918 influenza virus polymerase genes. Nature 437, 889–893.[CrossRef] [Google Scholar]
  32. WHO(2009). Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO, 1 July 2009. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_07_01/en/index.html.
  33. Yen, H. L., Lipatov, A. S., Ilyushina, N. A., Govorkova, E. A., Franks, J., Yilmaz, N., Douglas, A., Hay, A., Krauss, S. & other authors(2007). Inefficient transmission of H5N1 influenza viruses in a ferret contact model. J Virol 81, 6890–6898.[CrossRef] [Google Scholar]
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vol. , part 5, pp. 1284–1289

Comparison of avian- and human-like amino acids in viral proteins of influenza A viruses [ PDF] (105 KB)



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