Mapping of B-cell epitopes on the N- terminal and C-terminal segment of nucleocapsid protein from Crimean-Congo hemorrhagic fever virus

Abulimiti Moming; Daerken Tuoken; Xihong Yue; Wanxiang Xu; Rong Guo; Dongliang Liu; Yijie Li; Zhihong Hu; Fei Deng; Yujiang Zhang; Surong Sun

doi:10.1371/journal.pone.0204264

Mapping of B-cell epitopes on the N- terminal and C-terminal segment of nucleocapsid protein from Crimean-Congo hemorrhagic fever virus

PLoS One. 2018 Sep 20;13(9):e0204264. doi: 10.1371/journal.pone.0204264. eCollection 2018.

Authors

Abulimiti Moming¹, Daerken Tuoken¹, Xihong Yue², Wanxiang Xu³, Rong Guo², Dongliang Liu¹, Yijie Li¹, Zhihong Hu⁴, Fei Deng⁴, Yujiang Zhang², Surong Sun¹

Affiliations

¹ Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.
² Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, China.
³ Key Lab of Reproduction Regulation of NPFPC, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai, China.
⁴ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes severe disease in humans. CCHFV is widely distributed in more than 30 countries and distinct regions, which means that it poses a serious threat to human health. The nucleocapsid protein (NP) encoded by the CCHFV S gene is the primary detectable antigen in infected cells, which makes it an important viral antigen and a clinical diagnostic target. In this study, the modified biosynthetic peptide (BSP) method was used to identify the fine epitopes on the N- and C- terminals of NP from the CCHFV YL04057 strain using rabbit antiserum against CCHFV-NP. Nine epitopes were identified: E1a (178NLILNRGG185), E1b (184GGDENP189), E2 (352PLKWGKK358), E3 (363FADDS367), E4 (399NPDDAA404), E5a (447DIVASEHL454), E5b (452EHLLHQSL459), E6 (464SPFQNAY470) and E7 (475NATSANII482). Western blotting analysis showed that each epitope interacted with the positive serum of sheep that had been naturally infected with CCHFV. Amino acid sequence alignment between each epitope and their homologous proteins showed that they were almost 100% conserved among 12 CCHFV sequences from different lineages, except for epitopes E1a, E1b and E2. Three-dimensional structural modeling analysis showed that all identified epitopes were located on the surface of the NP "head" domain. This study identified fine epitopes on the N- and C- terminals of NP, which will increase the understanding of the structure and function of NP, and it could lay the foundation for the design and development of a CCHFV multi-epitope peptide vaccine and detection antigen.

Publication types

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

MeSH terms

Animals
Antibodies, Viral / metabolism
Conserved Sequence
Epitope Mapping / methods*
Epitopes, B-Lymphocyte / chemistry
Epitopes, B-Lymphocyte / immunology*
Hemorrhagic Fever Virus, Crimean-Congo / genetics
Hemorrhagic Fever Virus, Crimean-Congo / immunology*
Models, Molecular
Nucleocapsid Proteins / chemistry*
Nucleocapsid Proteins / genetics
Nucleocapsid Proteins / immunology
Protein Domains
Rabbits

Substances

Antibodies, Viral
Epitopes, B-Lymphocyte
Nucleocapsid Proteins

Grants and funding

This work was supported partly by the grants from the National Science Foundation of China (No. 81460303, 81760365 to SS), the Ministry of Science and Technology of China (2013FY113500), and Funded by the Open Research Fund Program of the State Key Laboratory of Virology of China (No. 2015IOV003 to FD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.