title: Crimean-Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity in bunyaviruses.
abstract: Crimean-Congo hemorrhagic fever virus (CCHFV), a virus with high mortality in humans, is a member of the genus Nairovirus in the family Bunyaviridae, and is a causative agent of severe hemorrhagic fever (HF). It is classified as a biosafety level 4 pathogen and a potential bioterrorism agent due to its aerosol infectivity and its ability to cause HF outbreaks with high case fatality (∼30%). However, little is known about the structural features and function of nucleoproteins (NPs) in the Bunyaviridae, especially in CCHFV. Here we report a 2.3-Å resolution crystal structure of the CCHFV nucleoprotein. The protein has a racket-shaped overall structure with distinct "head" and "stalk" domains and differs significantly with NPs reported so far from other negative-sense single-stranded RNA viruses. Furthermore, CCHFV NP shows a distinct metal-dependent DNA-specific endonuclease activity. Single residue mutations in the predicted active site resulted in a significant reduction in the observed endonuclease activity. Our results present a new folding mechanism and function for a negative-strand RNA virus nucleoprotein, extend our structural insight into bunyavirus NPs, and provide a potential target for antiviral drug development to treat CCHFV infection.
authors.affiliation: Laboratory of Structural Biology, School of Medicine and Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Wenming
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Maping
authors.initials: M
authors.lastname: Deng
authors.forename: Yuna
authors.initials: Y
authors.lastname: Sun
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Fei
authors.initials: F
authors.lastname: Deng
authors.forename: Hualin
authors.initials: H
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000378:metabolism; D004720:Endonucleases / Q000737:chemistry / Q000378:metabolism*; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000201:enzymology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry / Q000378:metabolism*; D016851:Orthobunyavirus / Q000201:enzymology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D009698:Nucleoproteins; D012315:RNA Caps; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D004720:Endonucleases