Bunyaviridae RdRps: structure, motifs, and RNA synthesis machinery

Bunyaviridae family is the largest and most diverse family of RNA viruses. It has more than 350 members divided into five genera: Orthobunyavirus, Phlebovirus, Nairovirus, Hantavirus, and Tospovirus. They are present in the five continents, causing recurrent epidemics, epizootics, and considerable agricultural loss. The genome of bunyaviruses is divided into three segments of negative single-stranded RNA according to their relative size: L (Large), M (Medium) and S (Small) segment. Bunyaviridae RNA-dependent RNA polymerase (RdRp) is encoded by the L segment, and is in charge of the replication and transcription of the viral RNA in the cytoplasm of the infected cell. Viral RdRps share a characteristic right hand-like structure with three subdomains: finger, palm, and thumb subdomains that define the formation of the catalytic cavity. In addition to the N-terminal endonuclease domain, eight conserved motifs (A-H) have been identified in the RdRp of Bunyaviridae. In this review, we have summarized the recent insights from the structural and functional studies of RdRp to understand the roles of different motifs shared by RdRps, the mechanism of viral RNA replication, genome segment packaging by the nucleoprotein, cap-snatching, mRNA transcription, and other RNA mechanisms of bunyaviruses.