Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling, as assessed by functional screening and assays. A helicase domain with intact ATPase activity was responsible for the dsRNA-mediated signaling. The caspase recruitment domain transmitted 'downstream' signals, resulting in the activation of transcription factors NF-κB and IRF-3. Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes.
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We thank E.L. Barsoumian for critical reading of the manuscript; S. Saito and M. Kohase for plaque assay protocol and suggestions; and M. Kohara for suggestions on real-time PCR. Supported by the Research for the Future Program; Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology of Japan; Nippon Boehringer Ingelheim; and Toray Industries.
The authors of this manuscript have filed a patent regarding RIG-I in collaboration with Toray Industries.
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Yoneyama, M., Kikuchi, M., Natsukawa, T. et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5, 730–737 (2004) doi:10.1038/ni1087
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