Cargando…

Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus

Canine distemper virus (CDV) infects many sensitive species worldwide and its host range is expanding. The hemagglutinin (H) protein, the major neutralizing target, binds to cellular receptors and subsequently triggers fusion for initial viral infection. So it’s necessary to clarify the precise neut...

Descripción completa

Detalles Bibliográficos
Autores principales: Bi, Zhenwei, Wang, Wenjie, Xia, Xingxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875009/
https://www.ncbi.nlm.nih.gov/pubmed/36713169
http://dx.doi.org/10.3389/fmicb.2022.1088243
_version_ 1784877866591191040
author Bi, Zhenwei
Wang, Wenjie
Xia, Xingxia
author_facet Bi, Zhenwei
Wang, Wenjie
Xia, Xingxia
author_sort Bi, Zhenwei
collection PubMed
description Canine distemper virus (CDV) infects many sensitive species worldwide and its host range is expanding. The hemagglutinin (H) protein, the major neutralizing target, binds to cellular receptors and subsequently triggers fusion for initial viral infection. So it’s necessary to clarify the precise neutralizing epitopes of H protein and extend the knowledge of mechanisms of virus neutralization. In this study, a neutralizing monoclonal antibody (mAb) 2D12 against CDV H protein, which had different reactivity with different CDV strains, was generated and characterized. A series of truncated H proteins were screened to define the minimal linear epitope 238DIEREFD244 recognized by 2D12. Further investigation revealed that the epitope was highly conserved in America-1 vaccine lineage of CDV strains, but different substitutions in the epitope appeared in CDV strains of the other lineages and two substitutions (D238Y and R241G) caused the change of antigenicity. Thus, the epitope represents a novel lineage-specific neutralizing target on H protein of CDV for differentiation of America-1 vaccine lineage and the other lineages of CDV strains. The epitope was identified to localize at the surface of H protein in two different positions in a three-dimensional (3D) structure, but not at the position of the receptor-binding site (RBS), so the mAb 2D12 that recognized the epitope did not inhibit binding of H protein to the receptor. But mAb 2D12 interfered with the H-F interaction for inhibiting membrane fusion, suggesting that the mAb plays key roles for formation of H-F protein oligomeric structure. Our data will contribute to the understanding of the structure, function, and antigenicity of CDV H protein and mechanisms of virus neutralization.
format Online
Article
Text
id pubmed-9875009
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-98750092023-01-26 Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus Bi, Zhenwei Wang, Wenjie Xia, Xingxia Front Microbiol Microbiology Canine distemper virus (CDV) infects many sensitive species worldwide and its host range is expanding. The hemagglutinin (H) protein, the major neutralizing target, binds to cellular receptors and subsequently triggers fusion for initial viral infection. So it’s necessary to clarify the precise neutralizing epitopes of H protein and extend the knowledge of mechanisms of virus neutralization. In this study, a neutralizing monoclonal antibody (mAb) 2D12 against CDV H protein, which had different reactivity with different CDV strains, was generated and characterized. A series of truncated H proteins were screened to define the minimal linear epitope 238DIEREFD244 recognized by 2D12. Further investigation revealed that the epitope was highly conserved in America-1 vaccine lineage of CDV strains, but different substitutions in the epitope appeared in CDV strains of the other lineages and two substitutions (D238Y and R241G) caused the change of antigenicity. Thus, the epitope represents a novel lineage-specific neutralizing target on H protein of CDV for differentiation of America-1 vaccine lineage and the other lineages of CDV strains. The epitope was identified to localize at the surface of H protein in two different positions in a three-dimensional (3D) structure, but not at the position of the receptor-binding site (RBS), so the mAb 2D12 that recognized the epitope did not inhibit binding of H protein to the receptor. But mAb 2D12 interfered with the H-F interaction for inhibiting membrane fusion, suggesting that the mAb plays key roles for formation of H-F protein oligomeric structure. Our data will contribute to the understanding of the structure, function, and antigenicity of CDV H protein and mechanisms of virus neutralization. Frontiers Media S.A. 2023-01-11 /pmc/articles/PMC9875009/ /pubmed/36713169 http://dx.doi.org/10.3389/fmicb.2022.1088243 Text en Copyright © 2023 Bi, Wang and Xia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Bi, Zhenwei
Wang, Wenjie
Xia, Xingxia
Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus
title Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus
title_full Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus
title_fullStr Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus
title_full_unstemmed Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus
title_short Structure and function of a novel lineage-specific neutralizing epitope on H protein of canine distemper virus
title_sort structure and function of a novel lineage-specific neutralizing epitope on h protein of canine distemper virus
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875009/
https://www.ncbi.nlm.nih.gov/pubmed/36713169
http://dx.doi.org/10.3389/fmicb.2022.1088243
work_keys_str_mv AT bizhenwei structureandfunctionofanovellineagespecificneutralizingepitopeonhproteinofcaninedistempervirus
AT wangwenjie structureandfunctionofanovellineagespecificneutralizingepitopeonhproteinofcaninedistempervirus
AT xiaxingxia structureandfunctionofanovellineagespecificneutralizingepitopeonhproteinofcaninedistempervirus