1887

Abstract

The reassortment of influenza viral gene segments plays a key role in the genesis of pandemic strains. All of the last three pandemic viruses contained reassorted polymerase complexes with subunits derived from animal viruses, suggesting that the acquisition of a reassorted polymerase complex might have a role in generating these pandemic viruses. Here, we studied polymerase activities of the pandemic H2N2, seasonal H2N2 and pandemic H3N2 viruses. We observed that the viral ribonucleoprotein (vRNP) of pandemic H2N2 virus has a highly robust activity. The polymerase activity of seasonal H2N2 viruses, however, was much reduced. We further identified three mutations (PB2-I114V, PB1-S261N and PA-D383N) responsible for the reduced activity. To determine the potential impact of viral polymerase activity on the viral life cycle, recombinant H3N2 viruses carrying pandemic and seasonal H2N2 vRNP were studied in cell cultures supplemented with oseltamivir carboxylate and tested for their abilities to develop adaptive or resistant mutations. It was found that the recombinant virus with pandemic H2N2 vRNP was more capable of restoring the viral fitness than the one with seasonal vRNP. These results suggest that a robust vRNP is advantageous to influenza virus to cope with a new selection pressure.

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2016-03-01
2019-10-23
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References

  1. Abe Y., Takashita E., Sugawara K., Matsuzaki Y., Muraki Y., Hongo S.. ( 2004;). Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin. J Virol 78: 9605–9611 [CrossRef] [PubMed].
    [Google Scholar]
  2. Chen L. M., Davis C. T., Zhou H., Cox N. J., Donis R. O.. ( 2008;). Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses. PLoS Pathog 4: e1000072 [CrossRef] [PubMed].
    [Google Scholar]
  3. Chin A. W., Li O. T., Mok C. K., Ng M. K., Peiris M., Poon L. L.. ( 2014;). Influenza A viruses with different amino acid residues at PB2-627 display distinct replication properties in vitro and in vivo: revealing the sequence plasticity of PB2-627 position. Virology 468–470: 545–555 [CrossRef] [PubMed].
    [Google Scholar]
  4. Daniels P. S., Jeffries S., Yates P., Schild G. C., Rogers G. N., Paulson J. C., Wharton S. A., Douglas A. R., Skehel J. J., Wiley D. C.. ( 1987;). The receptor-binding and membrane-fusion properties of influenza virus variants selected using anti-haemagglutinin monoclonal antibodies. EMBO J 6: 1459–1465 [PubMed].
    [Google Scholar]
  5. Ginting T. E., Shinya K., Kyan Y., Makino A., Matsumoto N., Kaneda S., Kawaoka Y.. ( 2012;). Amino acid changes in hemagglutinin contribute to the replication of oseltamivir-resistant H1N1 influenza viruses. J Virol 86: 121–127 [CrossRef] [PubMed].
    [Google Scholar]
  6. Gubareva L. V., Webster R. G., Hayden F. G.. ( 2002;). Detection of influenza virus resistance to neuraminidase inhibitors by an enzyme inhibition assay. Antiviral Res 53: 47–61 [CrossRef] [PubMed].
    [Google Scholar]
  7. Hara K., Nakazono Y., Kashiwagi T., Hamada N., Watanabe H.. ( 2013;). Co-incorporation of the PB2 and PA polymerase subunits from human H3N2 influenza virus is a critical determinant of the replication of reassortant ribonucleoprotein complexes. J Gen Virol 94: 2406–2416 [CrossRef] [PubMed].
    [Google Scholar]
  8. Hoffmann E., Neumann G., Kawaoka Y., Hobom G., Webster R. G.. ( 2000;). A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 97: 6108–6113 [CrossRef] [PubMed].
    [Google Scholar]
  9. Huang T. S., Palese P., Krystal M.. ( 1990;). Determination of influenza virus proteins required for genome replication. J Virol 64: 5669–5673 [PubMed].
    [Google Scholar]
  10. Kawaoka Y., Krauss S., Webster R. G.. ( 1989;). Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 63: 4603–4608 [PubMed].
    [Google Scholar]
  11. Kimble J. B., Sorrell E., Shao H., Martin P. L., Perez D. R.. ( 2011;). Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1 internal genes for transmission in the ferret model. Proc Natl Acad Sci U S A 108: 12084–12088 [CrossRef] [PubMed].
    [Google Scholar]
  12. Laeeq S., Smith C. A., Wagner S. D., Thomas D. B.. ( 1997;). Preferential selection of receptor-binding variants of influenza virus hemagglutinin by the neutralizing antibody repertoire of transgenic mice expressing a human immunoglobulin mu minigene. J Virol 71: 2600–2605 [PubMed].
    [Google Scholar]
  13. Li O. T., Chan M. C., Leung C. S., Chan R. W., Guan Y., Nicholls J. M., Poon L. L.. ( 2009;). Full factorial analysis of mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation. PLoS One 4: e5658 [CrossRef] [PubMed].
    [Google Scholar]
  14. 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 [CrossRef] [PubMed].
    [Google Scholar]
  15. Neumann G., Noda T., Kawaoka Y.. ( 2009;). Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459: 931–939 [CrossRef] [PubMed].
    [Google Scholar]
  16. Neumann G., Macken C. A., Kawaoka Y.. ( 2014;). Identification of amino acid changes that may have been critical for the genesis of A(H7N9) influenza viruses. J Virol 88: 4877–4896 [CrossRef] [PubMed].
    [Google Scholar]
  17. Palese P., Shaw M. L.. ( 2007;). Orthomyxoviridae: the viruses and their replication. . In Fields Virology, 5th edn., pp. 1647–1689. Edited by Knipe D. M., Howley P. M.. Philadelphia: Lippincott Williams & Wilkins;.
    [Google Scholar]
  18. Pflug A., Guilligay D., Reich S., Cusack S.. ( 2014;). Structure of influenza A polymerase bound to the viral RNA promoter. Nature 516: 355–360 [CrossRef] [PubMed].
    [Google Scholar]
  19. Pizzorno A., Abed Y., Plante P. L., Carbonneau J., Baz M., Hamelin M. E., Corbeil J., Boivin G.. ( 2014;). Evolution of oseltamivir resistance mutations in influenza A(H1N1) and A(H3N2) viruses during selection in experimentally infected mice. Antimicrob Agents Chemother 58: 6398–6405 [CrossRef] [PubMed].
    [Google Scholar]
  20. Smith G. J., Vijaykrishna D., Bahl J., Lycett S. J., Worobey M., Pybus O. G., Ma S. K., Cheung C. L., Raghwani J., other authors. ( 2009;). Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 459: 1122–1125 [CrossRef] [PubMed].
    [Google Scholar]
  21. Song J., Feng H., Xu J., Zhao D., Shi J., Li Y., Deng G., Jiang Y., Li X., other authors. ( 2011;). The PA protein directly contributes to the virulence of H5N1 avian influenza viruses in domestic ducks. J Virol 85: 2180–2188 [CrossRef] [PubMed].
    [Google Scholar]
  22. Song J., Xu J., Shi J., Li Y., Chen H.. ( 2015;). Synergistic effect of S224P and N383D substitutions in the PA of H5N1 avian influenza virus contributes to mammalian adaptation. Sci Rep 5: 10510 [CrossRef] [PubMed].
    [Google Scholar]
  23. Tai C. Y., Escarpe P. A., Sidwell R. W., Williams M. A., Lew W., Wu H., Kim C. U., Mendel D. B.. ( 1998;). Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071. Antimicrob Agents Chemother 42: 3234–3241 [PubMed].
    [Google Scholar]
  24. Takahashi T., Hashimoto A., Maruyama M., Ishida H., Kiso M., Kawaoka Y., Suzuki Y., Suzuki T.. ( 2009;). Identification of amino acid residues of influenza A virus H3 HA contributing to the recognition of molecular species of sialic acid. FEBS Lett 583: 3171–3174 [CrossRef] [PubMed].
    [Google Scholar]
  25. Webby R. J., Swenson S. L., Krauss S. L., Gerrish P. J., Goyal S. M., Webster R. G.. ( 2000;). Evolution of swine H3N2 influenza viruses in the United States. J Virol 74: 8243–8251 [CrossRef] [PubMed].
    [Google Scholar]
  26. Webster R. G., Laver W. G.. ( 1972;). The origin of pandemic influenza. Bull World Health Organ 47: 449–452 [PubMed].
    [Google Scholar]
  27. Wendel I., Rubbenstroth D., Doedt J., Kochs G., Wilhelm J., Staeheli P., Klenk H. D., Matrosovich M.. ( 2015;). The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus. J Virol 89: 4170–4179 [CrossRef] [PubMed].
    [Google Scholar]
  28. Yen H. L., Herlocher L. M., Hoffmann E., Matrosovich M. N., Monto A. S., Webster R. G., Govorkova E. A.. ( 2005;). Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother 49: 4075–4084 [CrossRef] [PubMed].
    [Google Scholar]
  29. Yen H. L., McKimm-Breschkin J. L., Choy K. T., Wong D. D., Cheung P. P., Zhou J., Ng I. H., Zhu H., Webby R. J., other authors. ( 2013;). Resistance to neuraminidase inhibitors conferred by an R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population. MBio 4: e00396–13 [CrossRef] [PubMed].
    [Google Scholar]
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