RIG-I reveals its perfect partner

Minton, Kirsty

doi:10.1038/nri1979

Research Highlight
Published: 17 November 2006

Viral immunity

RIG-I reveals its perfect partner

Kirsty Minton

Nature Reviews Immunology volume 6, page 876 (2006)Cite this article

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The potent type I interferon (IFN) response to viral infection has recently been shown to depend on the recognition of viral nucleic acids not only by membrane-associated Toll-like receptors, but also by the cytoplasmic RNA helicases RIG-I (retinoic-acid-inducible protein I) and MDA5 (melanoma differentiation-associated protein 5). However, it remains controversial how RIG-I and MDA5 discriminate between self and non-self RNAs. Two papers in Science report that, contrary to popular belief, 5′-triphosphate RNA, and not viral replication or the formation of double-stranded (ds)RNA, is the key to viral recognition by RIG-I.

Hornung et al. showed that whereas wild-type and MDA5-deficient cells produce large amounts of IFNβ in response to 5′-triphosphate RNA, no response was detected in RIG-I-deficient cells or cells expressing a dominant-negative RIG-I mutant. By contrast, overexpression of RIG-I increased the IFN response. The role of RIG-I in the detection of 5′-triphosphate viral RNA was also shown by Pichlmair et al.; RIG-I directly bound flu vRNA in vitro but formed a less stable complex with phosphatase-treated vRNA. Also, both groups showed that a 5′-triphosphate RNA could immunoprecipitate RIG-I, but not if the 5′-triphosphate group was enzymatically removed.

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ORIGINAL RESEARCH PAPERS

Pichlmair, A. et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′ phosphates. Science 12 October 2006 (doi:10.1126/science.1132998)
Hornung, V. et al. 5′-triphosphate RNA is the ligand for RIG-I. Science 12 October 2006 (doi:10.1126/science.1132505)

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