A Viral On/Off Switch for Interferon

摘要

The innate immune response to viral infection determines the course of the infection, and how quickly it will be subdued. Upon infection, emerging viruses such as the H5N1 variant of the influenza virus (1) and the coronavirus responsible for subacute airway respiratory syndrome (SARS) induce a storm of cy-tokine release by immune cells that results in substantial morbidity and mortality. Consequently, it is crucial to understand how viruses regulate the innate immune response. Viruses are potent inducers of antiviral cytokines called interferons (IFNs), but many of them can also block the synthesis and actions of IFNs. Two papers in this week's issue (2, 3) underscore the reciprocal relationship between viruses and IFNs by investigating IRF3, the critical transcription factor required for virus-induced IFN production. On page 1148, Sharma et al. (2) reveal the identity of the virus-activated kinases that activate IRF3. A complementary paper on page 1145 by Foy et al. (3) reports that hepatitis C virus (HCV) uses a viral protease to block IRF3 activation and IFN synthesis.