Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus

• DOI: 10.1073/pnas.0603082103
• Publication Date: 2006-05-20T00:43:53Z
• Authors: Leonid Gitlin; Winfried Barchet; Susan Gilfillan; Marina Cella; Bruce Beutler; Richard A. Flavell; Michael S. Diamond; Marco Colonna
• Keywords: TLR3; Picornavirus; MDA5; RNA Silencing; IRF3; RIG-I

The innate immune system recognizes viral dsRNA through two distinct pathways; the Toll-like receptor 3 (TLR3) pathway detects phagocytosed in endosomes; helicases retinoic acid-induced protein I (RIG-I) and melanoma differentiation-associated gene-5 (mda-5) detect cytoplasmic generated during replication. Both RIG-I mda-5 can bind polyriboinosinic:polyribocytidylic acid (polyI:C), synthetic analog of dsRNA, mediate type IFN responses to polyI:C multiple RNA viruses vitro. We mda-5-deficient mice showed that is dominant mediating secretion response vitro vivo. Moreover, mda-5-/- exhibited a selectively impaired antiviral encephalomyocarditis picornavirus, indicating functional specialization