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.


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  • Authors

    Guo Y

    Laboratory of Structural Biology, School of Medicine and Life Sciences, Tsinghua University, Beijing 100084, China.

    Wang W

    Ji W

    Deng M

    Sun Y

    Zhou H

    Yang C

    Deng F

    Wang H

    Hu Z

    Lou Z

    Rao Z


    Proceedings of the National Academy of Sciences of the United States of America 109:13 2012 Mar 27 pg 5046-51


    Chromatography, Gel
    Crystallography, X-Ray
    DNA, Viral
    Hemorrhagic Fever Virus, Crimean-Congo
    Host-Pathogen Interactions
    Models, Molecular
    Protein Structure, Secondary
    Protein Structure, Tertiary
    RNA Caps
    RNA-Binding Proteins
    Viral Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't



    PubMed ID