Interfering with Interferon

Science  02 Mar 2007:
Vol. 315, Issue 5816, pp. 1189n
DOI: 10.1126/science.315.5816.1189n

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 (TANK-binding kinase) and IKKϵ (an inhibitor of nuclear factor κB kinase) are also integral components of the IFNβ pathway. However, tenOever et al. (p. 1274) 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.

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