A Most Discerning Host

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Science  26 May 2006:
Vol. 312, Issue 5777, pp. 1107-1109
DOI: 10.1126/science.312.5777.1107e

Viruses can inadvertently announce their presence by displaying tell-tale patterns—often in the form of their own double-stranded (ds) RNA—and hosts have evolved a panoply of intracellular factors to detect and decode these signals and to set in motion a cascade of antiviral responses. Recently two pattern recognition receptors, RIG-1 and MDA-5, were found to act as RNA helicases and signaling adaptor proteins.

Kato et al. and Gitlin et al. show that RIG-1 and MDA-5 are distinct in their tastes for viral dsRNAs. Thus, mice lacking the MDA5 gene lost the ability to generate a type I interferon response to the dsRNA analog polyinosinic acid: polycytidylic acid [poly(I):poly(C)] and were more susceptible to infection with picornavirus. Kato et al. further compared this MDA5-dependent response with what happened in mice deficient in RIG-1 and found a requirement for RIG-1 in generating immunity to other dsRNA viruses, such as influenza and paramyxoviruses. With further antiviral dsRNA detectors likely to be discovered in mice and humans, elucidating the conformational or other features of dsRNA species important for selective pattern recognition would seem a useful avenue in the study of viral pathogenesis. — SJS

Nature 441, 101 (2006); Proc. Natl. Acad. Sci. U.S.A. 103, 10.1073/pnas.0603082103 (2006).

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