The RIG-I-like receptor family of immune proteins.

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are crucial cytosolic RNA sensors in the innate immune defense against virus infections. RLRs recognize defined molecular features in viral RNAs; however, virus infection can also trigger sensing of host-derived RNAs due to disturbances in host cell RNA processing, localization, or protein interactome. The activity and stability of RLRs are tightly controlled by various host proteins and post-translational modifications (PTMs), enabling protective antiviral immune responses when needed while preventing aberrant RLR activation. Recent studies revealed that metabolic reprogramming during virus infection regulates RLR signaling, while RLR responses, in turn, influence host metabolism. Furthermore, increasing evidence suggests that RLRs and various host cell processes are interregulated. In this review, we discuss the specific features of RLR ligands and how RLR signaling is regulated by host factors and PTMs. We also highlight how RLR signaling is integrated with other cellular processes, including metabolism, cytoskeleton dynamics, and autophagy.