Interfering with Interferon

Science's STKE  06 Mar 2007:
Vol. 2007, Issue 376, pp. tw81
DOI: 10.1126/stke.3762007tw81

The early host response to viral infection is regulated by the type I interferons (IFNα/β), which are induced after detection of virus-specific products. The subsequent transcriptional response is mediated via the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, which controls transcription of a range of interferon-stimulated genes (ISGs). The IKK-related kinases TBK and IKKε (an inhibitor of nuclear factor κB kinase) are also integral components of the IFNβ pathway. However, tenOever et al. reveal that, although mice deficient in IKKε are susceptible to viral infection, this susceptibility is not because of a loss of IFNβ expression. Rather, the deficiency resulted from an unanticipated downstream effect in which IKKε prevents homodimerization of STAT-1 by its phosphorylation. Instead, STAT-1 was incorporated into a heterotrimeric complex transcribing a distinct set of ISGs.

B. R. tenOever, S.-L. Ng, M. A. Chua, S. M. McWhirter, A. García-Sastre, T. Maniatis, Multiple functions of the IKK-related kinase IKKε in interferon-mediated antiviral immunity. Science 315, 1274-1278 (2007). [Abstract] [Full Text]