Three cytoplasmic RNA helicases, Retinoic acid Inducible Gene I (RIG-I), Melanoma Differentiation Associated gene 5 (MDA5), Laboratory of Genetics and Physiology 2 (LGP2), are collectively termed as RIG-I like receptors (RLR). RLRs reside in the cytoplasm and recognize RNA species produced in the cytoplasm. Whereas retinoic acid-inducible geneI (RIG-I) and Mda5 contain a DExD/H box RNA helicase domain and two caspase recruiting domain (CARD)-like domains required for eliciting downstream signaling pathways, LGP2 lacks the CARD-like domains. RIG-I and Mda5 are able to interact with viral RNA, albeit with different ligand specificity, and elicit signaling leading to the transcription of type I IFN and inflammatory cytokines. RLR signaling pathways converge at NF-κB, MAPK, and IRFs for a robust induction of type I IFN.
Interferon beta promoter stimulator-1 (IPS-1) [also known as mitochondrial antiviral signaling (MAVS), CARD adaptor inducing interferon beta (Cardif), or virus-induced signaling adaptor (VISA)] was discovered as an adaptor for RLR that provides a link between RLR and downstream signaling molecules. IPS-1 contains an N-terminal CARD-like domain sharing homology with those of RIG-I and Mda5. Overexpression of IPS-1 activates IFNα4, IFNα6, and NF-κB promoters as well as the IFNβ promoter and results in production of type I IFN that is sufficient for inhibition of viral replication. The induction of IFNβ by IPS-1 requires TBK1 and IKKi, as cells lacking these kinases together fail to activate the IFNβ promoter following IPS-1 overexpression.


1.Kawai T, et al. Ann N Y Acad Sci. 2008;1143:1–20.