Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity

The sensing of nucleic acids by DEAD/H-box helicases, specifically retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), plays a critical role in inducing antiviral immunity following infection. However, this DEAD/H-box helicase family includes many additional proteins whose immune functions have not been investigated. While numerous DEAD/H-box helicases contribute to antiviral immunity, they employ diverse mechanisms beyond the direct sensing of nucleic acids. Some members have also been identified to play proviral (promoting virus replication/propagation) roles during infections, regulate other non-viral infections, and contribute to the regulation of autoimmunity and cancer. This review synthesizes the known and emerging functions of the broader DEAD/H-box helicase family in immune regulation and highlights ongoing efforts to target these proteins therapeutically.