Fine Epitope Mapping of the Central Immunodominant Region of Nucleoprotein from Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

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...

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Vydáno v:PloS one Ročník 9; číslo 11; s. e108419
Hlavní autoři: Liu, Dongliang, Li, Yang, Zhao, Jing, Deng, Fei, Duan, Xiaomei, Kou, Chun, Wu, Ting, Li, Yijie, Wang, Yongxing, Ma, Ji, Yang, Jianhua, Hu, Zhihong, Zhang, Fuchun, Zhang, Yujiang, Sun, Surong
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 03.11.2014
Public Library of Science (PLoS)
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ISSN:1932-6203, 1932-6203
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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.
AbstractList 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.
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, 247 FDEAKK 252 ; E2a, 254 VEAL 257 ; E2b, 258 NGYLNKH 264 ; E3, 267 EVDKA 271 ; and E4, 274 DSMITN 279 ) identified through the use of rabbit antiserum, and one BCE (E5, 258 NGYL 261 ) 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.
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.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.
Author Kou, Chun
Zhang, Fuchun
Yang, Jianhua
Zhang, Yujiang
Liu, Dongliang
Deng, Fei
Wang, Yongxing
Li, Yijie
Zhao, Jing
Ma, Ji
Hu, Zhihong
Duan, Xiaomei
Sun, Surong
Li, Yang
Wu, Ting
AuthorAffiliation 2 State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
1 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China
3 Center for Disease Control and Prevention of the Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang, China
4 Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
Division of Clinical Research, United States of America
AuthorAffiliation_xml – name: 4 Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America
– name: 1 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China
– name: 3 Center for Disease Control and Prevention of the Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang, China
– name: 2 State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
– name: Division of Clinical Research, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/25365026$$D View this record in MEDLINE/PubMed
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Conceived and designed the experiments: SRS DLL YJZ FCZ. Performed the experiments: DLL YL JZ XMD CK TW. Analyzed the data: SRS DLL YJL JM YXW. Contributed reagents/materials/analysis tools: DLL SRS YJZ ZHH FD. Wrote the paper: DLL SRS JHY YJZ ZHH.
Competing Interests: The authors have declared that no competing interests exist.
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crossref_citationtrail_10_1371_journal_pone_0108419
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Snippet 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...
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StartPage e108419
SubjectTerms Amino Acid Sequence
Animal models
Animals
Antibodies - blood
Antibodies - immunology
Antigens
Biology and Life Sciences
Cancer
Conservation
Conserved Sequence
Crimean hemorrhagic fever
Diagnostic systems
Epitope Mapping
Epitopes, B-Lymphocyte - chemistry
Epitopes, B-Lymphocyte - immunology
Fever
Gene Expression
Genetic engineering
Genomes
Hemorrhage
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
Immunoglobulins
Laboratories
Life sciences
Lymphocytes B
Mapping
Models, Molecular
Molecular Sequence Data
Monoclonal antibodies
Nosocomial infections
Nucleocapsids
Nucleoproteins - chemistry
Nucleoproteins - genetics
Nucleoproteins - immunology
Nucleotide sequence
Peptide Fragments - chemistry
Peptide Fragments - genetics
Peptide Fragments - immunology
Peptides
Protein Conformation
Proteins
Reagents
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
S gene
Sequence Alignment
Sheep
Structural models
Studies
Three dimensional models
Viral diseases
Virology
Viruses
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Title Fine Epitope Mapping of the Central Immunodominant Region of Nucleoprotein from Crimean-Congo Hemorrhagic Fever Virus (CCHFV)
URI https://www.ncbi.nlm.nih.gov/pubmed/25365026
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http://dx.doi.org/10.1371/journal.pone.0108419
Volume 9
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