DDX58/IFIH1-mediated induction of interferon-alpha/beta

RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I, DDX58) and melanoma differentiation associated gene 5 (MDA5, IFIH1) are RNA helicases that recognize viral double-stranded RNA (dsRNA) present within the cytoplasm (Yoneyama M & Fujita T 2007, 2008). Upon viral infection dsRNA is generated by positive-strand RNA virus families such as Flaviviridae and Coronaviridae, negative-strand RNA virus families including Orthomyxoviridae and Paramyxoviridae, and DNA virus families such as Herpesviridae and Adenoviridae (Weber F et al. 2006; Son KN et al. 2015). Functionally RIG-I (DDX58) and MDA5 (IFIH1) positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. DDX58 (RIG-I) is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas IFIH1 (MDA5) is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription (Yoneyama M et al. 2004; Yoneyama M & Fujita T 2007, 2008).

Summary from Reactome (R-HSA-168928), read 2026-09-23.