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Volume 97, Issue 8

The NS1 gene from bat-derived influenza-like virus H17N10 can be rescued in influenza A PR8 backbone Free

Abstract

Influenza A viruses have the potential to cause pandemics due to the introduction of novel subtypes against which human hosts have little or no preexisting immunity. Such viruses may result from reassortment between human and animal influenza viruses. Recently, new influenza-like viruses were identified in bats, raising the concern for a new reservoir of potentially harmful influenza viruses that could form reassortants with categorized human influenza A viruses. However, until now, it has not been possible to generate a recombinant reassortant virus containing a single functional gene or domain from H17N10 that could propagate. Here, we demonstrate that a recombinant A/Puerto Rico/8/1934 (H1N1) virus with NS1 gene from H17N10 influenza-like virus can be successfully rescued. We used luciferase reporter assays and quantitative reverse transcriptase PCR to show that the NS1 protein from H17N10 inhibited Sendai-virus (SeV)-induced activation of IFN-β expression with an efficiency similar to NS1 from an H5N1 strain. Moreover, the crystal structure of the NS1 (H17N10) RNA-binding domain is also similar to that of other NS1s. These results demonstrate that H17N10 influenza-like virus indeed contains functional genes that are compatible with categorized influenza A viruses. Although the chance of this particular event occurring in nature seems negligible, further research is needed to address the possibility of the natural formation of reassortants.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): bat-derived , H17N10. , influenza-like virus , NEP protein , NS1 protein and reverse genetics
© 2016 The Authors
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2016-08-01
2024-04-19
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References

  1. Akarsu H., Burmeister W. P., Petosa C., Petit I., Müller C. W., Ruigrok R. W., Baudin F. 2003; Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2). EMBO J 22:4646–4655 [View Article][PubMed]
     [Google Scholar]
  2. Basler C. F., Reid A. H., Dybing J. K., Janczewski T. A., Fanning T. G., Zheng H., Salvatore M., Perdue M. L., Swayne D. E. et al. 2001; Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc Natl Acad Sci U S A 98:2746–2751 [View Article]
     [Google Scholar]
  3. Bornholdt Z. A., Prasad B. V. 2006; X-ray structure of influenza virus NS1 effector domain. Nat Struct Mol Biol 13:559–560 [View Article][PubMed]
     [Google Scholar]
  4. Bornholdt Z. A., Prasad B. V. 2008; X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus. Nature 456:985–988 [View Article][PubMed]
     [Google Scholar]
  5. Chen Z., Li Y., Krug R. M. 1999; Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3′-end processing machinery. EMBO J 18:2273–2283 [View Article][PubMed]
     [Google Scholar]
  6. Desselberger U., Racaniello V. R., Zazra J. J., Palese P. 1980; The 3′ and 5′-terminal sequences of influenza A, B and C virus RNA segments are highly conserved and show partial inverted complementarity. Gene 8:315–328 [View Article][PubMed]
     [Google Scholar]
  7. Donelan N. R., Basler C. F., García-Sastre A. 2003; A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice. J Virol 77:13257–13266 [View Article][PubMed]
     [Google Scholar]
  8. Gack M. U., Albrecht R. A., Urano T., Inn K. S., Huang I. C., Carnero E., Farzan M., Inoue S., Jung J. U., García-Sastre A. 2009; Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 5:439–449 [View Article][PubMed]
     [Google Scholar]
  9. Gao R., Cao B., Hu Y., Feng Z., Wang D., Hu W., Chen J., Jie Z., Qiu H. et al. 2013; Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368:1888–1897 [View Article][PubMed]
     [Google Scholar]
  10. García-Sastre A., Egorov A., Matassov D., Brandt S., Levy D. E., Durbin J. E., Palese P., Muster T. 1998; Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252:324–330 [View Article][PubMed]
     [Google Scholar]
  11. Hale B. G., Randall R. E., Ortín J., Jackson D. 2008; The multifunctional NS1 protein of influenza A viruses. J Gen Virol 89:2359–2376 [View Article][PubMed]
     [Google Scholar]
  12. Heaton N. S., Sachs D., Chen C.-J., Hai R., Palese P. 2013; Genome-wide mutagenesis of influenza virus reveals unique plasticity of the hemagglutinin and NS1 proteins. Proc Natl Acad Sci U S A 110:20248–20253 [View Article]
     [Google Scholar]
  13. 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 [View Article][PubMed]
     [Google Scholar]
  14. 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 [View Article][PubMed]
     [Google Scholar]
  15. Juozapaitis M., Aguiar Moreira É., Mena I., Giese S., Riegger D., Pohlmann A., Höper D., Zimmer G., Beer M. et al. 2014; An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus. Nat Commun 5:4448 [View Article][PubMed]
     [Google Scholar]
  16. Li J., Yu X., Pu X., Xie L., Sun Y., Xiao H., Wang F., Din H., Wu Y. et al. 2013; Environmental connections of novel avian-origin H7N9 influenza virus infection and virus adaptation to the human. Sci China Life Sci 56:485–492 [View Article][PubMed]
     [Google Scholar]
  17. Li Q., Sun X., Li Z., Liu Y., Vavricka C. J., Qi J., Gao G. F. 2012; Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus. Proc Natl Acad Sci U S A 109:18897–18902 [View Article][PubMed]
     [Google Scholar]
  18. Li S., Min J. Y., Krug R. M., Sen G. C. 2006; Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology 349:13–21 [View Article][PubMed]
     [Google Scholar]
  19. Li Y., Yamakita Y., Krug R. M. 1998; Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A 95:4864–4869 [View Article][PubMed]
     [Google Scholar]
  20. Liu D., Shi W., Shi Y., Wang D., Xiao H., Li W., Bi Y., Wu Y., Li X. 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 [View Article][PubMed]
     [Google Scholar]
  21. Liu J., Lynch P. A., Chien C. Y., Montelione G. T., Krug R. M., Berman H. M. 1997; Crystal structure of the unique RNA-binding domain of the influenza virus NS1 protein. Nat Struct Biol 4:896 –899 [View Article][PubMed]
     [Google Scholar]
  22. Luis A. D., Hayman D. T. S., O'Shea T. J., Cryan P. M., Gilbert A. T., Pulliam J. R. C., Mills J. N., Timonin M. E., Willis C. K. R. et al. 2013; A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?. Proc Biol Sci 280:1756 [View Article]
     [Google Scholar]
  23. Min J. Y., Krug R. M. 2006; The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: inhibiting the 2′-5′ oligo (A) synthetase/RNase L pathway. Proc Natl Acad Sci U S A 103:7100–7105 [View Article][PubMed]
     [Google Scholar]
  24. Min J. Y., Li S., Sen G. C., Krug R. M. 2007; A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology 363:236–243 [View Article][PubMed]
     [Google Scholar]
  25. Neumann G., Hughes M. T., Kawaoka Y. 2000; Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1. EMBO J 19:6751–6758 [View Article][PubMed]
     [Google Scholar]
  26. Paterson D., Fodor E. 2012; Emerging roles for the influenza A virus nuclear export protein (NEP). PLoS Pathog 8:e1003019 [View Article][PubMed]
     [Google Scholar]
  27. Pflug A., Guilligay D., Reich S., Cusack S. 2014; Structure of influenza A polymerase bound to the viral RNA promoter. Nature 516:355–360 [View Article][PubMed]
     [Google Scholar]
  28. Qian X. Y., Chien C. Y., Lu Y., Montelione G. T., Krug R. M. 1995; An amino-terminal polypeptide fragment of the influenza virus NS1 protein possesses specific RNA-binding activity and largely helical backbone structure. RNA 1:948–956[PubMed]
     [Google Scholar]
  29. Rajsbaum R., Albrecht R. A., Wang M. K., Maharaj N. P., Versteeg G. A., Nistal-Villán E., García-Sastre A., Gack M. U. 2012; Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog 8:e1003059 [View Article][PubMed]
     [Google Scholar]
  30. Shi Y., Wu Y., Zhang W., Qi J., Gao G. F. 2014; Enabling the ‘host jump’: structural determinants of receptor-binding specificity in influenza A viruses. Nat Rev Microbiol 12:822–831 [View Article][PubMed]
     [Google Scholar]
  31. Shi Z. 2010; Bat and virus. Protein Cell 1:109–114 [View Article][PubMed]
     [Google Scholar]
  32. Soubies S. M., Volmer C., Croville G., Loupias J., Peralta B., Costes P., Lacroux C., Guérin J. L., Volmer R. 2010; Species-specific contribution of the four C-terminal amino acids of influenza A virus NS1 protein to virulence. J Virol 84:6733–6747 [View Article][PubMed]
     [Google Scholar]
  33. Sun X., Shi Y., Lu X., He J., Gao F., Yan J., Qi J., Gao G. F. 2013; Bat-derived influenza hemagglutinin H17 does not bind canonical avian or human receptors and most likely uses a unique entry mechanism. Cell Rep 3:769–778 [View Article][PubMed]
     [Google Scholar]
  34. Tan S. L., Katze M. G. 1998; Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase. J Interferon Cytokine Res 18:757–766 [View Article][PubMed]
     [Google Scholar]
  35. Tefsen B., Lu G., Zhu Y., Haywood J., Zhao L., Deng T., Qi J., Gao G. F. 2013; The N-terminal domain of PA from bat-derived influenza-like virus H17N10 has endonuclease activity. J Virol 88:1935–1941 [View Article][PubMed]
     [Google Scholar]
  36. Tiley L. S., Hagen M., Matthews J. T., Krystal M. 1994; Sequence-specific binding of the influenza virus RNA polymerase to sequences located at the 5′ ends of the viral RNAs. J Virol 68:5108–5116[PubMed]
     [Google Scholar]
  37. Tong S., Li Y., Rivailler P., Conrardy C., Castillo D. A., Chen L. M., Recuenco S., Ellison J. A., Davis C. T. et al. 2012; A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A 109:4269–4274 [View Article][PubMed]
     [Google Scholar]
  38. Tong S., Zhu X., Li Y., Shi M., Zhang J., Bourgeois M., Yang H., Chen X., Recuenco S. et al. 2013; New World bats harbor diverse influenza A viruses. PLoS Pathog 9:e1003657 [View Article][PubMed]
     [Google Scholar]
  39. Turkington H. L., Juozapaitis M., Kerry P. S., Aydillo T., Ayllon J., García-Sastre A., Schwemmle M., Hale B. G. 2015; Novel bat influenza virus NS1 proteins bind double-stranded RNA and antagonize host innate immunity. J Virol 89:10696–10701 [View Article][PubMed]
     [Google Scholar]
  40. Wu A., Su C., Wang D., Peng Y., Liu M., Hua S., Li T., Gao G. F., Tang H. et al. 2013; Sequential reassortments underlie diverse influenza H7N9 genotypes in China. Cell Host Microbe 14:446–452 [View Article][PubMed]
     [Google Scholar]
  41. Wu Y., Gao G. F. 2013; Lessons learnt from the human infections of avian-origin influenza A H7N9 virus: live free markets and human health. Sci China Life Sci 56:493–494 [View Article][PubMed]
     [Google Scholar]
  42. Wu Y., Wu Y., Tefsen B., Shi Y., Gao G. F. 2014; Bat-derived influenza-like viruses H17N10 and H18N11. Trends Microbiol 22:183–191 [View Article][PubMed]
     [Google Scholar]
  43. Zheng H., Palese P., García-Sastre A. 1996; Nonconserved nucleotides at the 3′ and 5′ ends of an influenza A virus RNA play an important role in viral RNA replication. Virology 217:242–251 [View Article][PubMed]
     [Google Scholar]
  44. Zhou B., Ma J., Liu Q., Bawa B., Wang W., Shabman R. S., Duff M., Lee J., Lang Y. et al. 2014; Characterization of uncultivable bat influenza virus using a replicative synthetic virus. PLoS Pathog 10:e1004420 [View Article][PubMed]
     [Google Scholar]
  45. Zhu X., Yang H., Guo Z., Yu W., Carney P. J., Li Y., Chen L.-M., Paulson J. C., Donis R. O. et al. 2012; Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site. Proc Natl Acad Sci U S A 109:18903–18908 [View Article]
     [Google Scholar]
  46. Zhu X., Yu W., McBride R., Li Y., Chen L. M., Donis R. O., Tong S., Paulson J. C., Wilson I. A. 2013; Hemagglutinin homologue from H17N10 bat influenza virus exhibits divergent receptor-binding and pH-dependent fusion activities. Proc Natl Acad Sci U S A 110:1458–1463 [View Article][PubMed]
     [Google Scholar]
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The NS1 gene from bat-derived influenza-like virus H17N10 can be rescued in influenza A PR8 backbone
J. Gen. Virol. 97, 1797 (2016); https://doi.org/10.1099/jgv.0.000509
/content/journal/jgv/10.1099/jgv.0.000509
/content/journal/jgv/10.1099/jgv.0.000509
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