At least three major classes of PRRs contribute to the effective detection of flaviviruses—(1) toll-like receptors (in particular TLR 3 and 7), which sense viral RNA within the endosome; (2) retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) such as RIG-I itself and melanoma differentiation-associated protein 5 (MDA5), which recognize RNA species in the cytoplasm; and (3) cyclic GMP–AMP synthase (cGAS), which detects cellular dsDNA that is mislocalized during flavivirus infection [39,40,41,42]. The gene discussed is IFIH1; the disease is Flavivirus Infections.