Unbound MEDLINE

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.

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  • Authors

    Guo Y, Wang W, Ji W, Deng M, Sun Y, Zhou H, Yang C, Deng F, Wang H, Hu Z, Lou Z, Rao Z

    Institution

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

    Source

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

    MeSH

    Chromatography, Gel
    Crystallography, X-Ray
    DNA, Viral
    Endonucleases
    Hemorrhagic Fever Virus, Crimean-Congo
    Host-Pathogen Interactions
    Models, Molecular
    Nucleoproteins
    Orthobunyavirus
    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

    Language

    eng

    PubMed ID

    22421137