Fine epitope mapping of the central immunodominant region of nucleoprotein from Crimean-Congo hemorrhagic fever virus (CCHFV)

PLoS One. 2014 Nov 3;9(11):e108419. doi: 10.1371/journal.pone.0108419. eCollection 2014.

Abstract

Crimean-Congo hemorrhagic fever (CCHF), a severe viral disease known to have occurred in over 30 countries and distinct regions, is caused by the tick-borne CCHF virus (CCHFV). Nucleocapsid protein (NP), which is encoded by the S gene, is the primary antigen detectable in infected cells. The goal of the present study was to map the minimal motifs of B-cell epitopes (BCEs) on NP. Five precise BCEs (E1, 247FDEAKK252; E2a, 254VEAL257; E2b, 258NGYLNKH264; E3, 267EVDKA271; and E4, 274DSMITN279) identified through the use of rabbit antiserum, and one BCE (E5, 258NGYL261) recognized using a mouse monoclonal antibody, were confirmed to be within the central region of NP and were partially represented among the predicted epitopes. Notably, the five BCEs identified using the rabbit sera were able to react with positive serum mixtures from five sheep which had been infected naturally with CCHFV. The multiple sequence alignment (MSA) revealed high conservation of the identified BCEs among ten CCHFV strains from different areas. Interestingly, the identified BCEs with only one residue variation can apparently be recognized by the positive sera of sheep naturally infected with CCHFV. Computer-generated three-dimensional structural models indicated that all the antigenic motifs are located on the surface of the NP stalk domain. This report represents the first identification and mapping of the minimal BCEs of CCHFV-NP along with an analysis of their primary and structural properties. Our identification of the minimal linear BCEs of CCHFV-NP may provide fundamental data for developing rapid diagnostic reagents and illuminating the pathogenic mechanism of CCHFV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / blood
  • Antibodies / immunology
  • Conserved Sequence
  • Epitope Mapping*
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / immunology
  • Gene Expression
  • Hemorrhagic Fever Virus, Crimean-Congo / genetics
  • Hemorrhagic Fever Virus, Crimean-Congo / immunology*
  • Hemorrhagic Fever, Crimean / immunology
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleoproteins / chemistry
  • Nucleoproteins / genetics
  • Nucleoproteins / immunology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Protein Conformation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Sequence Alignment
  • Sheep

Substances

  • Antibodies
  • Epitopes, B-Lymphocyte
  • Immunodominant Epitopes
  • Nucleoproteins
  • Peptide Fragments
  • Recombinant Fusion Proteins

Grants and funding

This work was supported partly by Science and Technology Basic Work Program 2013FY113500 from Ministry of Science and Technology of China, the National Science Foundation of China (grant no. 81460303, 30860225), and the Open Research Fund Program of Xinjiang Key Laboratory of Biological Resources and Genetic Engineering (grant no. XJDX020l-2014-04). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.