Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5

Journal of Experimental Medicine - Tập 205 Số 7 - Trang 1601-1610 - 2008
Hiroki Kato1,2, Osamu Takeuchi1,2, Eriko Mikamo-Satoh3,4, Reiko Hirai5, Tomoji Kawai3, Kazufumi Matsushita1,2, Akane Hiiragi6, Terence S. Dermody7, Takashi Fujita5,6, Shizuo Akira1,2
11Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center,
22Research Institute for Microbial Diseases,
33Institute for Scientific and Industrial Research, Osaka University, Suita, Osaka 565-0871, Japan
44Department of Pharmacy, Hyogo University of Health Sciences, Cyuo-ku, Kobe, Hyogo 650-8530, Japan
55Laboratory of Molecular Genetics, Institute for Virus Research, and
66Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
77Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232

Tóm tắt

The ribonucleic acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons. Although 5′-triphosphate single-stranded RNA is a RIG-I ligand, the role of RIG-I and MDA5 in double-stranded (ds) RNA recognition remains to be characterized. In this study, we show that the length of dsRNA is important for differential recognition by RIG-I and MDA5. The MDA5 ligand, polyinosinic-polycytidylic acid, was converted to a RIG-I ligand after shortening of the dsRNA length. In addition, viral dsRNAs differentially activated RIG-I and MDA5, depending on their length. Vesicular stomatitis virus infection generated dsRNA, which is responsible for RIG-I–mediated recognition. Collectively, RIG-I detects dsRNAs without a 5′-triphosphate end, and RIG-I and MDA5 selectively recognize short and long dsRNAs, respectively.

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