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In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B

Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB, especially among children. Since the 21st century, EVB has been widely prevalent worldwide, and can cause serious diseases, such a...

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Autores principales: Wang, Hui, Fang, Yulu, Jia, Yongtao, Tang, Jiajie, Dong, Changzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461833/
https://www.ncbi.nlm.nih.gov/pubmed/37639390
http://dx.doi.org/10.1371/journal.pone.0290584
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author Wang, Hui
Fang, Yulu
Jia, Yongtao
Tang, Jiajie
Dong, Changzheng
author_facet Wang, Hui
Fang, Yulu
Jia, Yongtao
Tang, Jiajie
Dong, Changzheng
author_sort Wang, Hui
collection PubMed
description Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB, especially among children. Since the 21st century, EVB has been widely prevalent worldwide, and can cause serious diseases, such as viral meningitis, myocarditis, and neonatal sepsis. By using cryo-electron microscopy, the three-dimensional (3D) structures of EVB and their uncoating receptors (FcRn and CAR) have been determined, laying the foundation for the study of viral pathogenesis and therapeutic antibodies. A limited number of epitopes bound to neutralizing antibodies have also been determined. It is unclear whether additional epitopes are present or whether epitope mutations play a key role in molecular evolutionary history and epidemics, as in influenza and SARS-CoV-2. In the current study, the conformational epitopes of six representative EVB serotypes (E6, E11, E30, CVB1, CVB3 and CVB5) were systematically predicted by bioinformatics-based epitope prediction algorithm. We found that their epitopes were distributed into three clusters, where the VP1 BC loop, C-terminus and VP2 EF loop were the main regions of EVB epitopes. Among them, the VP1 BC loop and VP2 EF loop may be the key epitope regions that determined the use of the uncoating receptors. Further molecular evolution analysis based on the VP1 and genome sequences showed that the VP1 C-terminus and VP2 EF loop, as well as a potential “breathing epitope” VP1 N-terminus, were common mutation hotspot regions, suggesting that the emergence of evolutionary clades was driven by epitope mutations. Finally, footprints showed mutations were located on or near epitopes, while mutations on the receptor binding sites were rare. This suggested that EVB promotes viral epidemics by breaking the immune barrier through epitope mutations, but the mutations avoided the receptor binding sites. The bioinformatics study of EVB epitopes may provide important information for the monitoring and early warning of EVB epidemics and developing therapeutic antibodies.
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spelling pubmed-104618332023-08-29 In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B Wang, Hui Fang, Yulu Jia, Yongtao Tang, Jiajie Dong, Changzheng PLoS One Research Article Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB, especially among children. Since the 21st century, EVB has been widely prevalent worldwide, and can cause serious diseases, such as viral meningitis, myocarditis, and neonatal sepsis. By using cryo-electron microscopy, the three-dimensional (3D) structures of EVB and their uncoating receptors (FcRn and CAR) have been determined, laying the foundation for the study of viral pathogenesis and therapeutic antibodies. A limited number of epitopes bound to neutralizing antibodies have also been determined. It is unclear whether additional epitopes are present or whether epitope mutations play a key role in molecular evolutionary history and epidemics, as in influenza and SARS-CoV-2. In the current study, the conformational epitopes of six representative EVB serotypes (E6, E11, E30, CVB1, CVB3 and CVB5) were systematically predicted by bioinformatics-based epitope prediction algorithm. We found that their epitopes were distributed into three clusters, where the VP1 BC loop, C-terminus and VP2 EF loop were the main regions of EVB epitopes. Among them, the VP1 BC loop and VP2 EF loop may be the key epitope regions that determined the use of the uncoating receptors. Further molecular evolution analysis based on the VP1 and genome sequences showed that the VP1 C-terminus and VP2 EF loop, as well as a potential “breathing epitope” VP1 N-terminus, were common mutation hotspot regions, suggesting that the emergence of evolutionary clades was driven by epitope mutations. Finally, footprints showed mutations were located on or near epitopes, while mutations on the receptor binding sites were rare. This suggested that EVB promotes viral epidemics by breaking the immune barrier through epitope mutations, but the mutations avoided the receptor binding sites. The bioinformatics study of EVB epitopes may provide important information for the monitoring and early warning of EVB epidemics and developing therapeutic antibodies. Public Library of Science 2023-08-28 /pmc/articles/PMC10461833/ /pubmed/37639390 http://dx.doi.org/10.1371/journal.pone.0290584 Text en © 2023 Wang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Hui
Fang, Yulu
Jia, Yongtao
Tang, Jiajie
Dong, Changzheng
In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B
title In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B
title_full In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B
title_fullStr In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B
title_full_unstemmed In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B
title_short In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B
title_sort in silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus b
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461833/
https://www.ncbi.nlm.nih.gov/pubmed/37639390
http://dx.doi.org/10.1371/journal.pone.0290584
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