1887

Abstract

Highly pathogenic avian influenza (HPAI) H7N1 viruses caused a series of epizootics in Italy between 1999 and 2001. The emergence of these HPAI viruses coincided with the deletion of the six amino acids RVESEV at the C terminus of NS1. In order to assess how the truncation of NS1 affected virus replication, we used reverse genetics to generate a wild-type low-pathogenic avian influenza (LPAI) H7N1 virus with a 230aa NS1 (H7N1) and a mutant virus with a truncated NS1 (H7N1). The 6aa truncation had no impact on virus replication in duck or chicken cells . The H7N1 and H7N1 viruses also replicated to similar levels and induced similar immune responses in ducks or chickens. No significant histological lesions were detected in infected ducks, regardless of the virus inoculated. However, in chickens, the H7N1 virus induced a more severe interstitial pneumonia than did the H7N1 virus. These findings indicate that the C-terminal extremity of NS1, including the PDZ-binding motif ESEV, is dispensable for efficient replication of an LPAI virus in ducks and chickens, even though it may increase virulence in chickens, as revealed by the intensity of the histological lesions.

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2013-01-01
2024-04-20
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References

  1. Capua I., Alexander D. J. 2004; Avian influenza: recent developments. Avian Pathol 33:393–404 [View Article][PubMed]
    [Google Scholar]
  2. Dundon W. G., Capua I. 2009; A closer look at the NS1 of influenza virus. Viruses 1:1057–1072 [View Article][PubMed]
    [Google Scholar]
  3. Dundon W. G., Milani A., Cattoli G., Capua I. 2006; Progressive truncation of the non-structural 1 gene of H7N1 avian influenza viruses following extensive circulation in poultry. Virus Res 119:171–176 [View Article][PubMed]
    [Google Scholar]
  4. 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]
  5. 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]
  6. Garten R. J., Davis C. T., Russell C. A., Shu B., Lindstrom S., Balish A., Sessions W. M., Xu X., Skepner E.other authors 2009; Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325:197–201 [View Article][PubMed]
    [Google Scholar]
  7. Golebiewski L., Liu H., Javier R. T., Rice A. P. 2011; The avian influenza virus NS1 ESEV PDZ binding motif associates with Dlg1 and Scribble to disrupt cellular tight junctions. J Virol 85:10639–10648 [View Article][PubMed]
    [Google Scholar]
  8. 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]
  9. Hale B. G., Steel J., Manicassamy B., Medina R. A., Ye J., Hickman D., Lowen A. C., Perez D. R., García-Sastre A. 2010; Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus. J Gen Virol 91:1737–1742 [View Article][PubMed]
    [Google Scholar]
  10. Hoffmann T. W., Munier S., Larcher T., Soubieux D., Ledevin M., Esnault E., Tourdes A., Croville G., Guérin J. L.other authors 2012; Length variations in the NA stalk of an H7N1 influenza virus have opposite effects on viral excretion in chickens and ducks. J Virol 86:584–588 [View Article][PubMed]
    [Google Scholar]
  11. Holzinger D., Jorns C., Stertz S., Boisson-Dupuis S., Thimme R., Weidmann M., Casanova J. L., Haller O., Kochs G. 2007; Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling. J Virol 81:7776–7785 [View Article][PubMed]
    [Google Scholar]
  12. 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]
  13. Kida H., Yanagawa R., Matsuoka Y. 1980; Duck influenza lacking evidence of disease signs and immune response. Infect Immun 30:547–553[PubMed]
    [Google Scholar]
  14. 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]
  15. 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]
  16. Obenauer J. C., Denson J., Mehta P. K., Su X., Mukatira S., Finkelstein D. B., Xu X., Wang J., Ma J.other authors 2006; Large-scale sequence analysis of avian influenza isolates. Science 311:1576–1580 [View Article][PubMed]
    [Google Scholar]
  17. Pantin-Jackwood M. J., Swayne D. E. 2009; Pathogenesis and pathobiology of avian influenza virus infection in birds. Rev Sci Tech 28:113–136[PubMed]
    [Google Scholar]
  18. Schumacher B., Bernasconi D., Schultz U., Staeheli P. 1994; The chicken Mx promoter contains an ISRE motif and confers interferon inducibility to a reporter gene in chick and monkey cells. Virology 203:144–148 [View Article][PubMed]
    [Google Scholar]
  19. Sommereyns C., Paul S., Staeheli P., Michiels T. 2008; IFN-lambda (IFN-λ) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog 4:e1000017 [View Article][PubMed]
    [Google Scholar]
  20. 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]
  21. Spackman E., Gelb J. Jr, Preskenis L. A., Ladman B. S., Pope C. R., Pantin-Jackwood M. J., McKinley E. T. 2010; The pathogenesis of low pathogenicity H7 avian influenza viruses in chickens, ducks and turkeys. Virol J 7:331 [View Article][PubMed]
    [Google Scholar]
  22. Tonikian R., Zhang Y., Sazinsky S. L., Currell B., Yeh J. H., Reva B., Held H. A., Appleton B. A., Evangelista M.other authors 2008; A specificity map for the PDZ domain family. PLoS Biol 6:e239 [View Article][PubMed]
    [Google Scholar]
  23. Webster R. G., Yakhno M., Hinshaw V. S., Bean W. J., Copal Murti K. 1978; Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology 84:268–278 [View Article][PubMed]
    [Google Scholar]
  24. Zielecki F., Semmler I., Kalthoff D., Voss D., Mauel S., Gruber A. D., Beer M., Wolff T. 2010; Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein. J Virol 84:10708–10718 [View Article][PubMed]
    [Google Scholar]
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