ABSTRACT
RNA virus infection is recognized in the cell cytoplasm by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), comprised of RIG-I, melanoma differentiation-associated gene 5 (MDA5) and LGP2. RLRs are comprised of a DExD/H-box helicase domain and a C-terminal domain (CTD). Whereas RIG-I and MDA5 additionally harbor two caspase-recruitment domains (CARDs) for signaling, LGP2 lacks a CARD. Although LGP2 was hypothesized to function as the negative regulator in RLR-mediated virus recognition, a mouse study revealed that LGP2 is essential for positive regulation of MDA5-mediated viral recognition and is partially involved in the RIG-I-mediated responses. LGP2 induced Type I interferon production in an ATPase-dependent fashion. Although structural studies revealed that the CTD of LGP2 strongly binds dsRNA, transfected dsRNA activated cells independent of LGP2. Correctively, LGP2 functions upstream of MDA5 and RIG-I for sensing RNA virus infection; however, the precise mechanisms of its function are yet to be clarified.
