Multiple Functions of the IKK-Related Kinase IKKe in Interferon-Mediated Antiviral Immunity

KK{epsilon} is an IKK (inhibitor of nuclear factor {kappa}Bkinase)-related kinase implicated in virus induction of interferon-Beta (IFNBeta). We report that, although mice lacking IKK{epsilon} produce normal amounts of IFNBeta, 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 IFNBeta 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. [PUBLICATION ABSTRACT]