Structural and functional characterization of the severe fever with thrombocytopenia syndrome virus L protein. Issue 10 (20th April 2020)

• Record Type: Journal Article
• Authors: Vogel, Dominik; Thorkelsson, Sigurdur Rafn; Quemin, Emmanuelle R J; Meier, Kristina; Kouba, Tomas; Gogrefe, Nadja; Busch, Carola; Reindl, Sophia; Günther, Stephan; Cusack, Stephen; Grünewald, Kay; Rosenthal, Maria
• Is Part Of: Nucleic acids research. Volume 48:Issue 10(2020)
• Page Start: 5749
• Page End: 5765
• Publication Date: 2020-04-20
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkaa253
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential. The L protein of bunyaviruses is a multi-functional and multi-domain protein performing both virus transcription and genome replication and, therefore, is an ideal drug target. We established expression and purification procedures for the full-length L protein of SFTSV. By combining single-particle electron cryo-microscopy and X-ray crystallography, we obtained 3D models covering ∼70% of the SFTSV L protein in the apo-conformation including the polymerase core region, the endonuclease and the cap-binding domain. We compared this first L structure of the Phenuiviridae family to the structures of La Crosse peribunyavirus L protein and influenza orthomyxovirus polymerase. Together with a comprehensive biochemical characterization of the distinct functions of SFTSV L protein, this work provides a solid framework for future structural and functional studies of L protein–RNA interactions and the development of antiviral strategies against this group of emerging human pathogens.