Molecular Mechanisms of Viral RNA Detection: RIG-I and MDA5

The ability to distinguish “self” from “non-self” is fundamental to proper functioning of both the innate and adaptive immune systems. Several pattern recognition receptors (PRR) in the innate immune system are responsible for the initial detection of foreign molecules associated with pathogens such as bacterial cell wall components or viral nucleic acids. My laboratory has been interested in understanding the molecular mechanisms of one such family of receptors, RIG-I and MDA5, which recognize viral RNAs during infection and elicit the type I interferon response against a broad range of viruses. These receptors share the common domain architecture, including the DExD/H motif helicase domain. In this talk, I will present our recent discoveries on the structural and biochemical mechanisms by which these receptors differentially utilize the helicase domain to recognize their cognate viral RNAs and activate the signaling pathway.