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Sci. STKE, 6 March 2007
Vol. 2007, Issue 376, p. tw81
[DOI: 10.1126/stke.3762007tw81]

EDITORS' CHOICE

Immunology Interfering with Interferon

Stephen Simpson

Science, AAAS, Cambridge CB2 1LQ, UK

The early host response to viral infection is regulated by the type I interferons (IFN{alpha}/beta), 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 IKK{varepsilon} (an inhibitor of nuclear factor {kappa}B kinase) are also integral components of the IFNbeta pathway. However, tenOever et al. reveal that, although mice deficient in IKK{varepsilon} are susceptible to viral infection, this susceptibility is not because of a loss of IFNbeta expression. Rather, the deficiency resulted from an unanticipated downstream effect in which IKK{varepsilon} 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 IKK{varepsilon} in interferon-mediated antiviral immunity. Science 315, 1274-1278 (2007). [Abstract] [Full Text]

Citation: S. Simpson, Interfering with Interferon. Sci. STKE 2007, tw81 (2007).


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