VIROLOGY Making and Breaking an Antiviral Response

Viral infection activates type I interferon genes. This process requires the cooperative activation of several transcription factors, including interferon regulatory factor (IRF)-3 and IFR-7. Signals such as double-stranded RNA lead to the phosphorylation of IRF-3 and IRF-7 by a yet-uncharacterized virus-activated kinase (VAK). Sharma et al. now show that the component of VAK responsible for IRF-3 and IRF-7 phosphorylation is IKK-TBK-1, an IKK-related kinase complex. Foy et al. observed that the hepatitis C virus (HCV) serine protease (NS3/4A) blocks IFR-3 phosphorylation. Thus, HCV has evolved a mechanism of obstructing the cellular interferon response, potentially through the proteolytic cleavage of this IKK-TBK-1 complex.

S. Sharma, B. R. tenOever, N. Grandvaux, G.-P. Zhou, R. Lin, J. Hiscott, Triggering the interferon antiviral response through an IKK-related pathway. Science 300 1148-1151 (2003). [Abstract] [Full Text]

E. Foy, K. Li, C. Wang, R. Sumpter Jr., M. Ikeda, S. M. Lemon, M. Gale Jr., Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300, 1145-1148 (2003). [Abstract] [Full Text]

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REPORTS
Triggering the Interferon Antiviral Response Through an IKK-Related Pathway

Sonia Sharma, Benjamin R. tenOever, Nathalie Grandvaux, Guo-Ping Zhou, Rongtuan Lin, and John Hiscott (16 May 2003)
Science 300 (5622), 1148. [DOI: 10.1126/science.1081315]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »

REPORTS
Regulation of Interferon Regulatory Factor-3 by the Hepatitis C Virus Serine Protease

Eileen Foy, Kui Li, Chunfu Wang, Rhea Sumpter, Jr., Masanori Ikeda, Stanley M. Lemon, and Michael Gale, Jr. (16 May 2003)
Science 300 (5622), 1145. [DOI: 10.1126/science.1082604]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »