Title: Role of MDA5 in triggering of potent antiviral responses in the absence of type I IFN positive feedback (49.1)
Abstract: Abstract Viral recognition by specialized cellular sensors is critical for the innate immune response to virus infection. Detection of viral components by these sensors triggers the production of type I interferon (IFN), the earliest hallmark of viral infection, which plays an essential role in inducing an antiviral state in both infected and non-infected cells. Highly pathogenic respiratory viruses replicate in the lungs to high titers before a detectable anti-viral response begins, indicating that the viruses have devised effective mechanisms to avoid the innate anti-viral response. We have shown that dendritic cells can be potently activated in response to Sendai virus that contains a high dose of defective viral genomes (SeV HD) even in the absence of type I IFN signaling. The induction of anti-viral cytokines is driven by a quick and potent activation of IRF3 and NF-κB independently of IRF7. This response depends on the presence of MAVS that is essential for the signaling of the viral RNA sensors RIG-I and MDA5. Interestingly, our study indicates that infection with SeV HD triggers MDA5, but not RIG-I, in a type I IFN independent manner. This supports the hypothesis that the type I IFN-independent up-regulation of MDA5 is involved in the recognition of viral RNA and the subsequent induction of antiviral genes. In conclusion, this study suggests a previously unappreciated type I IFN independent function of MDA5 in the innate immune response to respiratory viruses.
Publication Year: 2011
Publication Date: 2011-04-01
Language: en
Type: article
Indexed In: ['crossref']
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