1
Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
2
Department of Vascular Biology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
3
Department of Chemistry and Biotechnology, School of Engineering, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
4
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
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-B 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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B 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.
