Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus
- 30 May 2006
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 103 (22), 8459-8464
- https://doi.org/10.1073/pnas.0603082103
Abstract
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.Keywords
This publication has 45 references indexed in Scilit:
- Pathogen Recognition and Innate ImmunityCell, 2006
- Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral responseNature, 2005
- Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6Nature, 2005
- Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virusNature, 2005
- VISA Is an Adapter Protein Required for Virus-Triggered IFN-β SignalingMolecular Cell, 2005
- Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3Cell, 2005
- IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon inductionNature Immunology, 2005
- Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine ExpressionJournal of Virology, 2005
- The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responsesNature Immunology, 2004
- Acre-transgenic mouse strain for the ubiquitous deletion ofloxP-flanked gene segments including deletion in germ cellsNucleic Acids Research, 1995