1887

Abstract

Currently circulating H5N1 influenza viruses have undergone a complex evolution since the appearance of their progenitor A/Goose/Guangdong/1/96 in 1996. After the eradication of the H5N1 viruses that emerged in Hong Kong in 1997 (HK/97 viruses), new genotypes of H5N1 viruses emerged in the same region in 2000 that were more pathogenic for both chickens and mice than HK/97 viruses. These, as well as virtually all highly pathogenic H5N1 viruses since 2000, harbour a deletion of aa 80–84 in the unstructured region of the non-structural (NS) protein NS1 linking its RNA-binding domain to its effector domain. NS segments harbouring this mutation have since been found in non-H5N1 viruses and we asked whether this 5 aa deletion could have a general effect not limited to the NS1 of H5N1 viruses. We genetically engineered this deletion in the NS segment of a duck-origin avian H1N1 virus, and compared the and properties of the WT and NSdel8084 viruses. In experimentally infected chickens, the NSdel8084 virus showed both an increased replication potential and an increased pathogenicity. This phenotype was correlated with a higher replicative efficiency , both in embryonated eggs and in a chicken lung epithelial cell line. Our data demonstrated that the increased replicative potential conferred by this small deletion was a general feature not restricted to NS1 from H5N1 viruses and suggested that viruses acquiring this mutation may be selected positively in the future.

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2014-06-01
2021-07-31
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References

  1. Aramini J. M., Ma L. C., Zhou L., Schauder C. M., Hamilton K., Amer B. R., Mack T. R., Lee H. W., Ciccosanti C. T.other authors 2011; Dimer interface of the effector domain of non-structural protein 1 from influenza A virus: an interface with multiple functions. J Biol Chem 286:26050–26060 [View Article][PubMed]
    [Google Scholar]
  2. 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]
  3. 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]
  4. Carrillo B., Choi J. M., Bornholdt Z. A., Sankaran B., Rice A. P., Prasad B. V. 2014; The influenza A virus protein NS1 displays structural polymorphism. J Virol 88:4113–4122 [View Article][PubMed]
    [Google Scholar]
  5. Cauthen A. N., Swayne D. E., Sekellick M. J., Marcus P. I., Suarez D. L. 2007; Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene. J Virol 81:1838–1847 [View Article][PubMed]
    [Google Scholar]
  6. 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]
  7. Duan L., Bahl J., Smith G. J., Wang J., Vijaykrishna D., Zhang L. J., Zhang J. X., Li K. S., Fan X. H.other authors 2008; The development and genetic diversity of H5N1 influenza virus in China, 1996–2006. Virology 380:243–254 [View Article][PubMed]
    [Google Scholar]
  8. Egorov A., Brandt S., Sereinig S., Romanova J., Ferko B., Katinger D., Grassauer A., Alexandrova G., Katinger H., Muster T. 1998; Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol 72:6437–6441[PubMed]
    [Google Scholar]
  9. Esnault E., Bonsergent C., Larcher T., Bed’hom B., Vautherot J. F., Delaleu B., Guigand L., Soubieux D., Marc D., Quéré P. 2011; A novel chicken lung epithelial cell line: characterization and response to low pathogenicity avian influenza virus. Virus Res 159:32–42 [View Article][PubMed]
    [Google Scholar]
  10. Falcón A. M., Marión R. M., Zürcher T., Gómez P., Portela A., Nieto A., Ortín J. 2004; Defective RNA replication and late gene expression in temperature-sensitive influenza viruses expressing deleted forms of the NS1 protein. J Virol 78:3880–3888 [View Article][PubMed]
    [Google Scholar]
  11. Fernandez-Sesma A., Marukian S., Ebersole B. J., Kaminski D., Park M. S., Yuen T., Sealfon S. C., García-Sastre A., Moran T. M. 2006; Influenza virus evades innate and adaptive immunity via the NS1 protein. J Virol 80:6295–6304 [View Article][PubMed]
    [Google Scholar]
  12. 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]
  13. 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]
  14. Guan Y., Peiris J. S., Lipatov A. S., Ellis T. M., Dyrting K. C., Krauss S., Zhang L. J., Webster R. G., Shortridge K. F. 2002a; Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proc Natl Acad Sci U S A 99:8950–8955 [View Article][PubMed]
    [Google Scholar]
  15. Guan Y., Peiris M., Kong K. F., Dyrting K. C., Ellis T. M., Sit T., Zhang L. J., Shortridge K. F. 2002b; H5N1 influenza viruses isolated from geese in Southeastern China: evidence for genetic reassortment and interspecies transmission to ducks. Virology 292:16–23 [View Article][PubMed]
    [Google Scholar]
  16. Hale B. G., Barclay W. S., Randall R. E., Russell R. J. 2008a; Structure of an avian influenza A virus NS1 protein effector domain. Virology 378:1–5 [View Article][PubMed]
    [Google Scholar]
  17. Hale B. G., Randall R. E., Ortín J., Jackson D. 2008b; The multifunctional NS1 protein of influenza A viruses. J Gen Virol 89:2359–2376 [View Article][PubMed]
    [Google Scholar]
  18. Jagger B. W., Wise H. M., Kash J. C., Walters K. A., Wills N. M., Xiao Y. L., Dunfee R. L., Schwartzman L. M., Ozinsky A.other authors 2012; An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 337:199–204 [View Article][PubMed]
    [Google Scholar]
  19. Kerry P. S., Ayllon J., Taylor M. A., Hass C., Lewis A., García-Sastre A., Randall R. E., Hale B. G., Russell R. J. 2011; A transient homotypic interaction model for the influenza A virus NS1 protein effector domain. PLoS ONE 6:e17946 [View Article][PubMed]
    [Google Scholar]
  20. Kochs G., Koerner I., Thiel L., Kothlow S., Kaspers B., Ruggli N., Summerfield A., Pavlovic J., Stech J., Staeheli P. 2007; Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens. J Gen Virol 88:1403–1409 [View Article][PubMed]
    [Google Scholar]
  21. Kowalinski E., Lunardi T., McCarthy A. A., Louber J., Brunel J., Grigorov B., Gerlier D., Cusack S. 2011; Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell 147:423–435 [View Article][PubMed]
    [Google Scholar]
  22. 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 [View Article][PubMed]
    [Google Scholar]
  23. Li K. S., Guan Y., Wang J., Smith G. J., Xu K. M., Duan L., Rahardjo A. P., Puthavathana P., Buranathai C.other authors 2004; Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430:209–213 [View Article][PubMed]
    [Google Scholar]
  24. Li W., Wang G., Zhang H., Xin G., Zhang D., Zeng J., Chen X., Xu Y., Cui Y., Li K. 2010; Effects of NS1 variants of H5N1 influenza virus on interferon induction, TNFalpha response and p53 activity. Cell Mol Immunol 7:235–242 [View Article][PubMed]
    [Google Scholar]
  25. Li W., Noah J. W., Noah D. L. 2011; Alanine substitutions within a linker region of the influenza A virus non-structural protein 1 alter its subcellular localization and attenuate virus replication. J Gen Virol 92:1832–1842 [View Article][PubMed]
    [Google Scholar]
  26. Liniger M., Summerfield A., Zimmer G., McCullough K. C., Ruggli N. 2012; Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2. J Virol 86:705–717 [View Article][PubMed]
    [Google Scholar]
  27. Long J. X., Peng D. X., Liu Y. L., Wu Y. T., Liu X. F. 2008; Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes 36:471–478 [View Article][PubMed]
    [Google Scholar]
  28. Marc D. 2012; NS1 des virus influenza: une protéine très "influente". Virologie 16:95–106
    [Google Scholar]
  29. Marc D., Barbachou S., Soubieux D. 2013; The RNA-binding domain of influenza virus non-structural protein-1 cooperatively binds to virus-specific RNA sequences in a structure-dependent manner. Nucleic Acids Res 41:434–449 [View Article][PubMed]
    [Google Scholar]
  30. Marión R. M., Aragón T., Beloso A., Nieto A., Ortín J. 1997; The N-terminal half of the influenza virus NS1 protein is sufficient for nuclear retention of mRNA and enhancement of viral mRNA translation. Nucleic Acids Res 25:4271–4277 [View Article][PubMed]
    [Google Scholar]
  31. Matrosovich M., Matrosovich T., Garten W., Klenk H. D. 2006; New low-viscosity overlay medium for viral plaque assays. Virol J 3:63 [View Article][PubMed]
    [Google Scholar]
  32. 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]
  33. Munier S., Larcher T., Cormier-Aline F., Soubieux D., Su B., Guigand L., Labrosse B., Cherel Y., Quéré P.other authors 2010; A genetically engineered waterfowl influenza virus with a deletion in the stalk of the neuraminidase has increased virulence for chickens. J Virol 84:940–952 [View Article][PubMed]
    [Google Scholar]
  34. Munir M., Zohari S., Iqbal M., Abbas M., Perez D. R., Berg M. 2013; The non-structural (NS) gene segment of H9N2 influenza virus isolated from backyard poultry in Pakistan reveals strong genetic and functional similarities to the NS gene of highly pathogenic H5N1. Virulence 4:612–623 [View Article][PubMed]
    [Google Scholar]
  35. Muramoto Y., Noda T., Kawakami E., Akkina R., Kawaoka Y. 2013; Identification of novel influenza A virus proteins translated from PA mRNA. J Virol 87:2455–2462 [View Article][PubMed]
    [Google Scholar]
  36. Nemeroff M. E., Qian X. Y., Krug R. M. 1995; The influenza virus NS1 protein forms multimers in vitro and in vivo . Virology 212:422–428 [View Article][PubMed]
    [Google Scholar]
  37. Nemeroff M. E., Barabino S. M., Li Y., Keller W., Krug R. M. 1998; Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3′ end formation of cellular pre-mRNAs. Mol Cell 1:991–1000 [View Article][PubMed]
    [Google Scholar]
  38. Nguyen T., Rivailler P., Davis C. T., Hoa D. T., Balish A., Dang N. H., Jones J., Vui D. T., Simpson N.other authors 2012; Evolution of highly pathogenic avian influenza (H5N1) virus populations in Vietnam between 2007 and 2010. Virology 432:405–416 [View Article][PubMed]
    [Google Scholar]
  39. Palese P., Shaw M. 2007; Orthomyxoviridae: the viruses and their replication. Fields Virology, 5th edn. pp. 1647–1689 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  40. Rice P., Longden I., Bleasby A. 2000; emboss: the European Molecular Biology Open Software Suite. Trends Genet 16:276–277 [View Article][PubMed]
    [Google Scholar]
  41. Robb N. C., Fodor E. 2012; The accumulation of influenza A virus segment 7 spliced mRNAs is regulated by the NS1 protein. J Gen Virol 93:113–118 [View Article][PubMed]
    [Google Scholar]
  42. Satterly N., Tsai P. L., van Deursen J., Nussenzveig D. R., Wang Y., Faria P. A., Levay A., Levy D. E., Fontoura B. M. 2007; Influenza virus targets the mRNA export machinery and the nuclear pore complex. Proc Natl Acad Sci U S A 104:1853–1858 [View Article][PubMed]
    [Google Scholar]
  43. Shapira S. D., Gat-Viks I., Shum B. O. V., Dricot A., de Grace M. M., Wu L., Gupta P. B., Hao T., Silver S. J.other authors 2009; A physical and regulatory map of host–influenza interactions reveals pathways in H1N1 infection. Cell 139:1255–1267 [View Article][PubMed]
    [Google Scholar]
  44. Soubies S. M., Hoffmann T. W., Croville G., Larcher T., Ledevin M., Soubieux D., Quéré P., Guérin J. L., Marc D., Volmer R. 2013; Deletion of the C-terminal ESEV domain of NS1 does not affect the replication of a low-pathogenic avian influenza virus H7N1 in ducks and chickens. J Gen Virol 94:50–58 [View Article][PubMed]
    [Google Scholar]
  45. Talon J., Horvath C. M., Polley R., Basler C. F., Muster T., Palese P., García-Sastre A. 2000; Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 74:7989–7996 [View Article][PubMed]
    [Google Scholar]
  46. Vijaykrishna D., Bahl J., Riley S., Duan L., Zhang J. X., Chen H., Peiris J. S., Smith G. J., Guan Y. 2008; Evolutionary dynamics and emergence of panzootic H5N1 influenza viruses. PLoS Pathog 4:e1000161 [View Article][PubMed]
    [Google Scholar]
  47. Wang Z., Robb N. C., Lenz E., Wolff T., Fodor E., Pleschka S. 2010; NS reassortment of an H7-type highly pathogenic avian influenza virus affects its propagation by altering the regulation of viral RNA production and antiviral host response. J Virol 84:11323–11335 [View Article][PubMed]
    [Google Scholar]
  48. Wise H. M., Foeglein A., Sun J., Dalton R. M., Patel S., Howard W., Anderson E. C., Barclay W. S., Digard P. 2009; A complicated message: identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J Virol 83:8021–8031 [View Article][PubMed]
    [Google Scholar]
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