Crimean-Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity in bunyaviruses.
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.
Laboratory of Structural Biology, School of Medicine and Life Sciences, Tsinghua University, Beijing 100084, China.
SourceProceedings of the National Academy of Sciences of the United States of America 109:13 2012 Mar 27 pg 5046-51
Hemorrhagic Fever Virus, Crimean-Congo
Protein Structure, Secondary
Protein Structure, Tertiary
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't