MDA-5

MDA-5, also known as MDA5 or IFIH1, is the RIG-I-like receptor specialized in recognizing long double-stranded RNA, the replication intermediate of many picornaviruses such as encephalomyocarditis virus. Sharing the CARD-helicase-CTD layout with RIG-I, it instead binds RNA cooperatively in a length-dependent filament, then signals through MAVS to launch type I interferon responses. Beyond antiviral defense, the IFIH1 gene harbors a well-known nonsynonymous variant associated with susceptibility to type 1 diabetes, and gain-of-function mutations cause Aicardi-Goutieres syndrome and other interferonopathies. Recombinant MDA-5 supports studies of RNA-sensing thresholds, viral antagonism, and autoimmune interferon signatures.