Multiple functions of the IKK-related kinase IKKε in interferon-mediated antiviral immunity

IKK epsilon is an IKK ( inhibitor of nuclear factor kappa B kinase)-related kinase implicated in virus induction of interferon-beta (IFN beta). We report that, although mice lacking IKK epsilon produce normal amounts of IFN beta, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKK epsilon because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKK epsilon is activated by IFN beta and that IKK epsilon directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKK epsilon plays a critical role in the IFN-inducible antiviral transcriptional response.