Activation of interferon regulatory factor 3 is inhibited by the influenza a virus NS1 protein

J. Talon, C. M. Horvath, R. Polley, C. F. Basler, T. Muster, P. Palese*, A. Garcia-Sastre

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

464 Scopus citations

Abstract

We present a novel mechanism by which viruses may inhibit the alpha/beta interferon (IFN-α/β) cascade. The double-stranded RNA (dsRNA) binding protein NS1 of influenza virus is shown to prevent the potent antiviral interferon response by inhibiting the activation of interferon regulatory factor 3 (IRF-3), a key regulator of IFN-α/β gene expression. IRF-3 activation and, as a consequence, IFN-β mRNA induction are inhibited in wild-type (PR8) influenza virus-infected cells but not in cells infected with an isogenic virus lacking the NS1 gene (delNS1 virus). Furthermore, NS1 is shown to be a general inhibitor of the interferon signaling pathway. Inhibition of IRF-3 activation can be achieved by the expression of wild-type NS1 in trans, not only in delNS1 virus-infected cells but also in cells infected with a heterologous RNA virus (Newcastle disease virus). We propose that inhibition of IRF-3 activation by a dsRNA binding protein significantly contributes to the virulence of influenza A viruses and possibly to that of other viruses.

Original languageEnglish (US)
Pages (from-to)7989-7996
Number of pages8
JournalJournal of virology
Volume74
Issue number17
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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