The Mechanism of Genome Replication and Transcription in Bunyaviruses

The Bunyavirales order constitutes a diverse group of predominantly insect and rodent-borne viruses with a segmented, negative sense single-stranded RNA genome, which infect a wide range of vertebrate, invertebrate and plant hosts. Some bunyaviruses such as Lassa fever virus, Rift Valley fever virus, and Crimean Congo hemorrhagic fever virus are of serious public health concern as emphasized by their inclusion in the WHO R&D Blueprint list of priority diseases. While the viral large (L) polymerase protein containing the RNA-dependent RNA polymerase serves as the central factor of the viral replication cycle, and thus a suitable antiviral drug target, comparative knowledge about the structure and activities of this multifunctional protein across bunyaviruses has been limited and scattered in different literatures. Therefore, this study compiled the current information about the structures of the bunyavirus L proteins, and highlights the differences and commonalities in their genome replication and transcription processes as revealed by advanced cryogenic electron microscopy studies. In particular, insights into the 5' RNA hook coordination, distal duplex conformation, and 3' template RNA sequestration; viral genome replication priming, elongation, and termination; as well as viral transcription and cap-snatching mechanism were explained. In addition, the role of additional viral and host proteins, and comparison between bunyaviruses and the related influenza virus polymerase complexes were itemized to highlight sweeping questions for further research.
(BNU)