DEAD-box RNA helicases: The driving forces behind RNA metabolism at the crossroad of viral replication and antiviral innate immunity

DEAD-box RNA helicases, the largest family of superfamily 2 helicases, are a profoundly conserved family of RNA-binding proteins, containing a distinctive Asp?Glu?Ala?Asp (D-E-A-D) sequence motif, which is the origin of their name. Aside from the ATP-dependent unwinding of RNA duplexes, which set up these proteins as RNA helicases, DEAD-box proteins have been found to additionally stimulate RNA duplex fashioning and to uproot proteins from RNA, aiding the reformation of RNA and RNA-protein complexes. There is accumulating evidence that DEAD-box helicases play functions in the recognition of foreign nucleic acids and the modification of viral infection. As intracellular parasites, viruses must avoid identification by innate immune sensing mechanisms and disintegration by cellular machinery, whilst additionally exploiting host cell activities to assist replication. The capability of DEAD-box helicases to sense RNA in a sequence-independent way, as well as the broadness of cellular roles performed by members of this family, drive them to affect innate sensing and viral infections in numerous manners. Undoubtedly, DEAD-box helicases have been demonstrated to contribute to intracellular immune recognition, function as antiviral effectors, and even to be exploited by viruses to support their replication. Relying on the virus or the viral cycle phase, a DEAD-box helicase can function either in a proviral manner or as an antiviral factor. This review gives a comprehensive perspective on the various biochemical characteristics of DEAD-box helicases and their links to structural data. It additionally outlines the multiple functions that members of the DEAD-box helicase family play during viral infections.