RIG-I-like receptors: Sensing and responding to RNA virus infection

Viral and microbial pathogens contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). RNA virus infection is also detected through TLR-independent mechanisms. Early viral replicative intermediates are detected by two recently characterized cystolic viral RNA receptors—RIG-I and MDA-5. Both are DExDH/box RNA helicases, and RIG-I specifically recognizes 5′-triphosphate containing viral RNA and transmits signals that induce type I interferon-mediated host immunity against virus infection. In this review, we will focus on RIG-I-like receptor (RLR) signal transduction and the regulatory mechanisms – ubiquitination, deubiquitination, ISGylation – underlying this important host response.