Helicase specificity
RIG-I and Mda5 are cytoplasmic helicases that act as sensors for double-stranded RNA and RNA viruses. In Nature, Kato et al. demonstrate that RIG-I and Mda5 have different specificities for RNA ligands. Mice deficient in Mda5 but not those deficient in RIG-I fail to produce interferon-/ in response to poly(I)poly(C). Embryonic fibroblasts from these 'knockout' mice further distinguish the responses of the helicases, as RIG-I is essential for the interferon response to in vitro–transcribed double-stranded RNA, paramyxoviruses, influenza virus and Japanese encephalitis RNA viruses, whereas Mda5 is required for picornaviruses only. Virus infection of RIG-I- and Mda5-deficient mice demonstrates that the helicase-virus specificity extends to an in vivo setting. Thus, RIG-I and Mda5 helicases are differentially required for host defense against RNA viruses.
