Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity.
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.
Yoneyama
Mitsutoshi
M
Antiviral Innate Immunity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Honkomagome, Tokyo, Japan.
Kikuchi
Mika
M
Matsumoto
Kanae
K
Imaizumi
Tadaatsu
T
Miyagishi
Makoto
M
Taira
Kazunari
K
Foy
Eileen
E
Loo
Yueh-Ming
YM
Gale
Michael
M
Akira
Shizuo
S
Yonehara
Shin
S
Kato
Atsushi
A
Fujita
Takashi
T
D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry / Q000502:physiology*; D011971:Receptors, Immunologic; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology*
D011971:Receptors, Immunologic; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases