Aryl hydrocarbon receptor interacting protein targets IRF7 to suppress antiviral signaling and the induction of type I interferon [Signal Transduction]

April 24th, 2015 by Zhou, Q., Lavorgna, A., Bowman, M., Hiscott, J., Harhaj, E. W.

The transcription factor interferon regulatory factor 7 (IRF7) is a key regulator of type I interferon and plays essential roles in restricting virus infection and spread. IRF7 activation is tightly regulated to prevent excessive inflammation and autoimmunity; however, how IRF7 is suppressed by negative regulators remains poorly understood. Here, we have identified aryl hydrocarbon receptor interacting protein (AIP) as a new binding partner of IRF7. The interaction between AIP and IRF7 is enhanced upon virus infection, and AIP potently inhibits IRF7-induced type I IFN (IFNα/β) production. Overexpression of AIP blocks virus-induced activation of IFN, whereas knockdown of AIP by siRNA potentiates viral-activated IFN production. Consistently, AIP-deficient murine embryonic fibroblasts are highly resistant to virus infection due to increased production of IFNα/β. AIP inhibits IRF7 function by antagonizing the nuclear localization of IRF7. Together, our study identifies AIP as a novel inhibitor of IRF7 and negative regulator of innate antiviral signaling.
  • Posted in Journal of Biological Chemistry, Publications
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