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. 2013 May 23;4(6):445–455. doi: 10.1007/s13238-013-3901-4

The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

Honggang Zhou 1,2, Yuna Sun 4, Ying Wang 5, Min Liu 1,5, Chao Liu 1,5, Wenming Wang 1,5, Xiang Liu 5, Le Li 1,5, Fei Deng 3, Hualin Wang 3,✉, Yu Guo 1,✉, Zhiyong Lou 2,✉
PMCID: PMC4875558  PMID: 23702688

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), a member of the Phlebovirus genus from the Bunyaviridae family endemic to China, is the causative agent of life-threatening severe fever with thrombocytopenia syndrome (SFTS), which features high fever and hemorrhage. Similar to other negative-sense RNA viruses, SFTSV encodes a nucleocapsid protein (NP) that is essential for viral replication. NP facilitates viral RNA encapsidation and is responsible for the formation of ribonucleoprotein complex. However, recent studies have indicated that NP from Phlebovirus members behaves in inhomogeneous oligomerization states. In the present study, we report the crystal structure of SFTSV NP at 2.8 Å resolution and demonstrate the mechanism by which it processes a ringshaped hexameric form to accomplish RNA encapsidation. Key residues essential for oligomerization are identified through mutational analysis and identified to have a significant impact on RNA binding, which suggests that correct formation of highly ordered oligomers is a critical step in RNA encapsidation. The findings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-013-3901-4 and is accessible for authorized users.

Keywords: SFTSV, nucleoprotein, oligomer, RNP assembly, crystal structure

Electronic supplementary material

13238_2013_3901_MOESM1_ESM.pdf (493KB, pdf)

Supplementary material, approximately 493 KB.

Footnotes

These authors contributed equally to the work.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-013-3901-4 and is accessible for authorized users.

Contributor Information

Hualin Wang, Email: h.wang@wh.iov.cn.

Yu Guo, Email: guoyu@nankai.edu.cn.

Zhiyong Lou, Email: louzy@xtal.tsinghua.edu.cn.

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Supplementary Materials

13238_2013_3901_MOESM1_ESM.pdf (493KB, pdf)

Supplementary material, approximately 493 KB.

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