Structural insights into Rift Valley fever virus replication machinery

Abstract

Rift Valley fever virus (RVFV) belongs to the order Bunyavirales and is the type species of genus Phlebovirus, which accounts for over 50% of family Phenuiviridae species. RNA-dependent RNA polymerase (L protein) is responsible for facilitating the replication and transcription of the virus. We report two cryo-EM RVFV L protein structures at 3.6 Å and 3.8 Å resolution in the presence and absence of RNA, respectively. In this first L protein structure of genus Phlebovirus, viral RNA induces considerable conformational changes of the polymerase. The RVFV L protein priming loop is distinctly different from those of other L proteins and undergoes large movements related to its replication elongation role. Structural and biochemical analyses indicate that a single template can initiate RNA replication, which is notably enhanced by 5’ viral RNA. These findings advance our understanding of RNA synthesis mechanism and provide a basis for antiviral inhibitor development.

Comparative study of two Rift Valley fever virus field strains circulating in Mauritania in 2010 and 2013 reveals the high virulence of the MRU25010-30 strain isolated from camel

“…L protein is the viral RNA-dependent RNA polymerase (RdRp) involved in the transcription and replication processes as well as cap-snatching mechanism [59,60]. D157G is located in the endonuclease domain while D407G and G411S are part of the Arch domain, within PA-C like domain [61]. Finally, T2033A is located at the C terminal part of the RdRp within the PB-2 like domain [60].…”