Type I interferons (IFNalpha/beta) are central mediators for antiviral responses. Using a functional cloning strategy, we have identified a molecule designated IPS-1. IPS-1 overexpression caused antiviral responses by producing type I IFN and IFN-inducible genes through activation of IRF3, IRF7 and NF-kappaB. TBK1 and IKKi protein kinases were required for the IPS-1-mediated IFN induction. IPS-1 contains an N-terminal caspase recruiting domain (CARD)-like structure that mediates interaction with the CARD of RIG-I and Mda5, cytoplasmic RNA helicases sensing RNA viruses. Reduction of IPS-1 by siRNA blocked IFN induction by virus infection. Thus, IPS-1 is an adapter that mediates RIG-I- and Mda5-dependent antiviral responses.
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