Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.
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 (polyI:C), the synthetic analog of viral dsRNA, and mediate type I IFN responses to polyI: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 polyI: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.
Gitlin
Leonid
L
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Barchet
Winfried
W
Gilfillan
Susan
S
Cella
Marina
M
Beutler
Bruce
B
Flavell
Richard A
RA
Diamond
Michael S
MS
Colonna
Marco
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility; D004686:Encephalomyocarditis virus / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011119:Polynucleotides / Q000276:immunology*; D020365:RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
D007370:Interferon Type I; D011119:Polynucleotides; C049667:poly(rI).poly(dC); C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases