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: Yu Guo, Wenming Wang, Wei Ji, Maping Deng, Yuna Sun, Honggang Zhou, Cheng Yang, Fei Deng, Hualin Wang, Zhihong Hu, Zhiyong Lou, Zihe Rao
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 109 Issue 13 Pg. 5046-51 (Mar 27 2012) ISSN: 1091-6490 [Electronic] United States
• PMID: 22421137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Nucleoproteins
• RNA Caps
• RNA-Binding Proteins
• Viral Proteins
• Endonucleases

Topics

• Chromatography, Gel
• Crystallography, X-Ray
• DNA, Viral (metabolism)
• Endonucleases (chemistry, metabolism)
• Hemorrhagic Fever Virus, Crimean-Congo (enzymology)
• Host-Pathogen Interactions (immunology)
• Models, Molecular
• Nucleoproteins (chemistry, metabolism)
• Orthobunyavirus (enzymology)
• Protein Structure, Secondary
• Protein Structure, Tertiary
• RNA Caps (metabolism)
• RNA-Binding Proteins (metabolism)
• Viral Proteins (chemistry, metabolism)