1887

Abstract

The NS1 gene of influenza A virus encodes a multi-functional protein that plays an important role in counteracting cellular antiviral mechanisms such as the interferon (IFN), protein kinase R and retinoic acid-inducible gene product I pathways. In addition, NS1 has recently been shown to have RNA interference (RNAi) or RNA silencing suppression (RSS) activity. This study analysed the IFN antagonistic activity of NS1 and the RSS activity for several influenza subtypes: H1N1, H3N2, H5N1 and H7N7. It was shown that the various NS1 proteins were capable of inhibiting the activation of an IFN-responsive promoter. However, differential RSS activity was measured among the NS1 variants. The NS1 protein of strain A/WSN/33 (H1N1) was most potent in suppressing short hairpin RNA-mediated gene silencing. In contrast, NS1 proteins of the highly pathogenic H5N1 strains A/VN/1194/04 and A/HK/156/97 were most potent in complementing the RSS function of the human immunodeficiency virus type 1 Tat protein. These results show that the ability of NS1 to suppress RNAi varies among influenza strains and is likely to contribute to differences in viral replication capacity and pathogenicity.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.008284-0
2009-08-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/8/1916.html?itemId=/content/journal/jgv/10.1099/vir.0.008284-0&mimeType=html&fmt=ahah

References

  1. Andersson M. G., Haasnoot P. C. J., Xu N., Berenjian S., Berkhout B., Akusjarvi G. 2005; Suppression of RNA interference by adenovirus virus-associated RNA. J Virol 79:9556–9565 [CrossRef]
    [Google Scholar]
  2. Bennasser Y., Le S. Y., Benkirane M., Jeang K. T. 2005; Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity 22:607–619 [CrossRef]
    [Google Scholar]
  3. Bergmann M., García-Sastre A., Carnero E., Pehamberger H., Wolff K., Palese P., Muster T. 2000; Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication. J Virol 74:6203–6206 [CrossRef]
    [Google Scholar]
  4. Bucher E., Hemmes H., de Haan P., Goldbach R., Prins M. 2004; The influenza A virus NS1 protein binds small interfering RNAs and suppresses RNA silencing in plants. J Gen Virol 85:983–991 [CrossRef]
    [Google Scholar]
  5. Cronin S., Verchot J., Haldeman-Cahill R., Schaad M. C., Carrington J. C. 1995; Long-distance movement factor: a transport function of the potyvirus helper component proteinase. Plant Cell 7:549–559 [CrossRef]
    [Google Scholar]
  6. Delgadillo M. O., Sáenz P., Salvador B., García J. A., Simón-Mateo C. 2004; Human influenza virus NS1 protein enhances viral pathogenicity and acts as an RNA silencing suppressor in plants. J Gen Virol 85:993–999 [CrossRef]
    [Google Scholar]
  7. de Vries W., Berkhout B. 2008; RNAi suppressors encoded by pathogenic human viruses. Int J Biochem Cell Biol 40:2007–2012 [CrossRef]
    [Google Scholar]
  8. de Vries W., Haasnoot J., van der Velden J., van Montfort T., Zorgdrager F., Paxton W., Cornelissen M., van Kuppeveld F., de Haan P., Berkhout B. 2008; Increased virus replication in mammalian cells by blocking intracellular innate defense responses. Gene Ther 15:545–552 [CrossRef]
    [Google Scholar]
  9. Ding S. W., Li W. X., Symons R. H. 1995; A novel naturally occurring hybrid gene encoded by a plant RNA virus facilitates long distance virus movement. EMBO J 14:5762–5772
    [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 [CrossRef]
    [Google Scholar]
  11. Guo Z., Chen L. M., Zeng H., Gomez J. A., Plowden J., Fujita T., Katz J. M., Donis R. O., Sambhara S. 2007; NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I. Am J Respir Cell Mol Biol 36:263–269 [CrossRef]
    [Google Scholar]
  12. Haasnoot J., de Vries W., Geutjes E. J., Prins M., de Haan P., Berkhout B. 2007; The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog 3:e86 [CrossRef]
    [Google Scholar]
  13. Huang J., Wang F., Argyris E., Chen K., Liang Z., Tian H., Huang W., Squires K., Verlinghieri G., Zhang H. 2007; Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 13:1241–1247 [CrossRef]
    [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 [CrossRef]
    [Google Scholar]
  15. Kasschau K. D., Carrington J. C. 1998; A counterdefensive strategy of plant viruses: suppression of posttranscriptional gene silencing. Cell 95:461–470 [CrossRef]
    [Google Scholar]
  16. Kok K. H., Jin D. Y. 2006; Influenza A virus NS1 protein does not suppress RNA interference in mammalian cells. J Gen Virol 87:2639–2644 [CrossRef]
    [Google Scholar]
  17. Lecellier C. H., Dunoyer P., Arar K., Lehmann-Che J., Eyquem S., Himber C., Saib A., Voinnet O. 2005; A cellular microRNA mediates antiviral defense in human cells. Science 308:557–560 [CrossRef]
    [Google Scholar]
  18. Li W. X., Li H., Lu R., Li F., Dus M., Atkinson P., Brydon E. W., Johnson K. L., García-Sastre A. other authors 2004; Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc Natl Acad Sci U S A 101:1350–1355 [CrossRef]
    [Google Scholar]
  19. Li Z., Jiang Y., Jiao P., Wang A., Zhao F., Tian G., Wang X., Yu K., Bu Z., Chen H. 2006; The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol 80:11115–11123 [CrossRef]
    [Google Scholar]
  20. Lipatov A. S., Andreansky S., Webby R. J., Hulse D. J., Rehg J. E., Krauss S., Perez D. R., Doherty P. C., Webster R. G., Sangster M. Y. 2005; Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol 86:1121–1130 [CrossRef]
    [Google Scholar]
  21. Lu S., Cullen B. R. 2004; Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and microRNA biogenesis. J Virol 78:12868–12876 [CrossRef]
    [Google Scholar]
  22. Ludwig S., Wang X., Ehrhardt C., Zheng H., Donelan N., Planz O., Pleschka S., García-Sastre A., Heins G., Wolff T. 2002; The influenza A virus NS1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. J Virol 76:11166–11171 [CrossRef]
    [Google Scholar]
  23. Matskevich A. A., Moelling K. 2007; Dicer is involved in protection against influenza A virus infection. J Gen Virol 88:2627–2635 [CrossRef]
    [Google Scholar]
  24. Mibayashi M., Martinez-Sobrido L., Loo Y. M., Cardenas W. B., Gale M., Jr & García-Sastre A. 2007; Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol 81:514–524 [CrossRef]
    [Google Scholar]
  25. 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 [CrossRef]
    [Google Scholar]
  26. 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 [CrossRef]
    [Google Scholar]
  27. Otsuka M., Jing Q., Georgel P., New L., Chen J., Mols J., Kang Y. J., Jiang Z., Du X. other authors 2007; Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 27:123–134 [CrossRef]
    [Google Scholar]
  28. Parameswaran P., Fire A., Jalili R., Gharizadeh B., Ronaghi M., Lu R., Ding S. W., Burgon T., Jackson W. other authors 2008; Investigating the interplay between viral replication and the RNAi machinery in vertebrates and invertebrates. In Proceedings of the Keystone Symposiap– 127 (poster abstract number 258) 25–30, March 2008 Vancouver, Canada:
    [Google Scholar]
  29. Schott D. H., Cureton D. K., Whelan S. P., Hunter C. P. 2005; An antiviral role for the RNA interference machinery in Caenorhabditis elegans . Proc Natl Acad Sci U S A 102:18420–18424 [CrossRef]
    [Google Scholar]
  30. Segers G. C., Zhang X., Deng F., Sun Q., Nuss D. L. 2007; Evidence that RNA silencing functions as an antiviral defense mechanism in fungi. Proc Natl Acad Sci U S A 104:12902–12906 [CrossRef]
    [Google Scholar]
  31. Seo S. H., Hoffmann E., Webster R. G. 2002; Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8:950–954 [CrossRef]
    [Google Scholar]
  32. Triboulet R., Mari B., Lin Y. L., Chable-Bessia C., Bennasser Y., Lebrigand K., Cardinaud B., Maurin T., Barbry P. other authors 2007; Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315:1579–1582 [CrossRef]
    [Google Scholar]
  33. Wang X., Li M., Zheng H., Muster T., Palese P., Beg A. A., García-Sastre A. 2000; Influenza A virus NS1 protein prevents activation of NF- κ B and induction of alpha/beta interferon. J Virol 74:11566–11573 [CrossRef]
    [Google Scholar]
  34. Wang Y., Kato N., Jazag A., Dharel N., Otsuka M., Taniguchi H., Kawabe T., Omata M. 2006; Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response. Gastroenterology 130:883–892 [CrossRef]
    [Google Scholar]
  35. Wilkins C., Dishongh R., Moore S. C., Whitt M. A., Chow M., Machaca K. 2005; RNA interference is an antiviral defence mechanism in Caenorhabditis elegans . Nature 436:1044–1047 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.008284-0
Loading
/content/journal/jgv/10.1099/vir.0.008284-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error