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      Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus.

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          Abstract

          The retinoic acid-inducible gene I product (RIG-I) has been identified as a cellular sensor of RNA virus infection resulting in beta interferon (IFN-beta) induction. However, many viruses are known to encode viral products that inhibit IFN-beta production. In the case of influenza A virus, the viral nonstructural protein 1 (NS1) prevents the induction of the IFN-beta promoter by inhibiting the activation of transcription factors, including IRF-3, involved in IFN-beta transcriptional activation. The inhibitory properties of NS1 appear to be due at least in part to its binding to double-stranded RNA (dsRNA), resulting in the sequestration of this viral mediator of RIG-I activation. However, the precise effects of NS1 on the RIG-I-mediated induction of IFN-beta have not been characterized. We now report that the NS1 of influenza A virus interacts with RIG-I and inhibits the RIG-I-mediated induction of IFN-beta. This inhibition was apparent even when a mutant RIG-I that is constitutively activated (in the absence of dsRNA) was used to trigger IFN-beta production. Coexpression of RIG-I, its downstream signaling partner, IPS-1, and NS1 resulted in increased levels of RIG-I and NS1 within an IPS-1-rich, solubilization-resistant fraction after cell lysis. These results suggest that RIG-I, IPS-1, and NS1 become part of the same complex. Consistent with this idea, NS1 was also found to inhibit IFN-beta promoter activation by IPS-1 overexpression. Our results indicate that, in addition to sequestering dsRNA, the NS1 of influenza A virus binds to RIG-I and inhibits downstream activation of IRF-3, preventing the transcriptional induction of IFN-beta.

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          Author and article information

          Journal
          J Virol
          Journal of virology
          American Society for Microbiology
          0022-538X
          0022-538X
          Jan 2007
          : 81
          : 2
          Affiliations
          [1 ] Department of Microbiology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA.
          Article
          JVI.01265-06
          10.1128/JVI.01265-06
          1797471
          17079289
          95a0b621-b478-48c2-8c0f-d8efb9207350
          History

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