FIG. 1.

Endogenous RNA recognition by RIG-I-like receptors. Recognition of endogenous RNAs by RIG-I and/or MDA5 during viral infection (a) or in inflammatory and autoimmune diseases (b). Specific RNA ligands are depicted as well as the signaling pathway initiated by RIG-I and MDA5 via their adaptor protein MAVS, which is localized at the mitochondrion. Activation of MAVS then leads to several downstream signaling events, including the activation of TBK-1, IKKɛ, IRF3, IRF7, and NF-κB. The detailed mechanisms of host ligand recognition by RLRs are described in the text. Solid lines indicate direct effects or signaling events. Dashed lines indicate signaling events that are indirect. Red lines indicate inhibitory effects. CARD, caspase activation and recruitment domain; CTD, carboxy-terminal domain; EBV, Epstein-Barr virus; HSV-1, herpes simplex virus type 1; IAV, influenza A virus; IKKɛ, IκB kinase-ɛ; IFN, interferon; IRF, IFN regulatory factor; KSHV, Kaposi's sarcoma-associated herpesvirus; MDA5, melanoma differentiation-associated protein 5; MAVS, mitochondrial antiviral signaling protein; NF-κB, nuclear factor-κB; P, phosphate; RIG-I, retinoic acid-inducible gene-I; TBK-1, TANK-binding kinase 1; VSV, vesicular stomatitis virus. Color images are available online.