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Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity

2005; American Association of Immunologists; Volume: 175; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.175.5.2851

1550-6606

Mitsutoshi Yoneyama, Mika Kikuchi, Kanae Matsumoto, Tadaatsu Imaizumi, Makoto Miyagishi, Kazunari Taira, Eileen Foy, Yueh–Ming Loo, Michael Gale, Shizuo Akira, Shin Yonehara, Atsushi Kato, Takashi Fujita,

Cytokine Signaling Pathways and Interactions

Abstract The cellular protein retinoic acid-inducible gene I (RIG-I) senses intracellular viral infection and triggers a signal for innate antiviral responses including the production of type I IFN. RIG-I contains a domain that belongs to a DExD/H-box helicase family and exhibits an N-terminal caspase recruitment domain (CARD) homology. There are three genes encoding RIG-I-related proteins in human and mouse genomes. Melanoma differentiation associated gene 5 (MDA5), which consists of CARD and a helicase domain, functions as a positive regulator, similarly to RIG-I. Both proteins sense viral RNA with a helicase domain and transmit a signal downstream by CARD; thus, these proteins share overlapping functions. Another protein, LGP2, lacks the CARD homology and functions as a negative regulator by interfering with the recognition of viral RNA by RIG-I and MDA5. The nonstructural protein 3/4A protein of hepatitis C virus blocks the signaling by RIG-I and MDA5; however, the V protein of the Sendai virus selectively abrogates the MDA5 function. These results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.