TY - JOUR
T1 - Essential role of mda-5 in type I IFN responses to polyriboinosinic
T2 - polyribocytidylic acid and encephalomyocarditis picornavirus
AU - Gitlin, Leonid
AU - Barchet, Winfried
AU - Gilfillan, Susan
AU - Cella, Marina
AU - Beutler, Bruce
AU - Flavell, Richard A.
AU - Diamond, Michael S.
AU - Colonna, Marco
PY - 2006/5/30
Y1 - 2006/5/30
N2 - The innate immune system recognizes viral dsRNA through two distinct pathways; the Toll-like receptor 3 (TLR3) pathway detects dsRNA phagocytosed in endosomes; the helicases retinoic acid-induced protein I (RIG-I) and melanoma differentiation-associated gene-5 (mda-5) detect cytoplasmic dsRNA generated during viral replication. Both RIG-I and mda-5 can bind polyriboinosinic: polyribocytidylic acid (polyl:C), the synthetic analog of viral dsRNA, and mediate type I IFN responses to polyl:C and multiple RNA viruses in vitro. We generated mda-5-deficient mice and showed that mda-5 is the dominant receptor mediating type I IFN secretion in response to polyl:C in vitro and in vivo. Moreover, mda-5-/- mice exhibited a selectively impaired antiviral response to encephalomyocarditis picornavirus, indicating functional specialization of mda-5 in vivo.
AB - The innate immune system recognizes viral dsRNA through two distinct pathways; the Toll-like receptor 3 (TLR3) pathway detects dsRNA phagocytosed in endosomes; the helicases retinoic acid-induced protein I (RIG-I) and melanoma differentiation-associated gene-5 (mda-5) detect cytoplasmic dsRNA generated during viral replication. Both RIG-I and mda-5 can bind polyriboinosinic: polyribocytidylic acid (polyl:C), the synthetic analog of viral dsRNA, and mediate type I IFN responses to polyl:C and multiple RNA viruses in vitro. We generated mda-5-deficient mice and showed that mda-5 is the dominant receptor mediating type I IFN secretion in response to polyl:C in vitro and in vivo. Moreover, mda-5-/- mice exhibited a selectively impaired antiviral response to encephalomyocarditis picornavirus, indicating functional specialization of mda-5 in vivo.
KW - Innate immunity
KW - Virus
UR - http://www.scopus.com/inward/record.url?scp=33744791510&partnerID=8YFLogxK
U2 - 10.1073/pnas.0603082103
DO - 10.1073/pnas.0603082103
M3 - Article
C2 - 16714379
AN - SCOPUS:33744791510
SN - 0027-8424
VL - 103
SP - 8459
EP - 8464
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -