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Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease

Coxsackievirus A6 (CVA6) is a key pathogen causing hand, foot and mouth disease (HFMD). However, there are currently no specific antiviral drugs or vaccines for treating infections caused by CVA6. In this study, human rhabdomyosarcoma (RD), African green monkey kidney (Vero), and human embryonic lun...

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Autores principales: Liu, Hongbo, Zhang, Ming, Feng, Changzeng, Cong, Shanri, Xu, Danhan, Sun, Hao, Yang, Zhaoqing, Ma, Shaohui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418080/
https://www.ncbi.nlm.nih.gov/pubmed/34490141
http://dx.doi.org/10.3389/fcimb.2021.700191
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author Liu, Hongbo
Zhang, Ming
Feng, Changzeng
Cong, Shanri
Xu, Danhan
Sun, Hao
Yang, Zhaoqing
Ma, Shaohui
author_facet Liu, Hongbo
Zhang, Ming
Feng, Changzeng
Cong, Shanri
Xu, Danhan
Sun, Hao
Yang, Zhaoqing
Ma, Shaohui
author_sort Liu, Hongbo
collection PubMed
description Coxsackievirus A6 (CVA6) is a key pathogen causing hand, foot and mouth disease (HFMD). However, there are currently no specific antiviral drugs or vaccines for treating infections caused by CVA6. In this study, human rhabdomyosarcoma (RD), African green monkey kidney (Vero), and human embryonic lung diploid fibroblast (KMB17) cells were used to isolate CVA6 from 327 anal swab and fecal samples obtained during HFMD monitoring between 2009 and 2017. The VP1 genes of the isolates were sequenced and genotyped, and the biological characteristics of the representative CVA6 strains were analyzed. A total of 37 CVA6 strains of the D3 gene subtypes were isolated from RD cells, all of which belonged to the epidemic strains in mainland China. Using the adaptive culture method, 10 KMB17 cell-adapted strains were obtained; however, no Vero cell-adapted strains were acquired. Among the KMB17 cell-adapted strains, only KYN-A1205 caused disease or partial death in suckling mice, and its virulence was stronger than its RD cell-adapted strain. The pathogenic KYN-A1205 strain caused strong tropism to the muscle tissue and led to pathological changes, including muscle necrosis and nuclear fragmentation in the forelimb and hindlimb. Sequence analysis demonstrated that the KYN-A1205 strain exhibited multiple amino acid mutations after KMB17 cell adaptation. Moreover, it showed strong pathogenicity, good immunogenicity and genetic stability, and could be used as an experimental CVA6 vaccine candidate.
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spelling pubmed-84180802021-09-05 Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease Liu, Hongbo Zhang, Ming Feng, Changzeng Cong, Shanri Xu, Danhan Sun, Hao Yang, Zhaoqing Ma, Shaohui Front Cell Infect Microbiol Cellular and Infection Microbiology Coxsackievirus A6 (CVA6) is a key pathogen causing hand, foot and mouth disease (HFMD). However, there are currently no specific antiviral drugs or vaccines for treating infections caused by CVA6. In this study, human rhabdomyosarcoma (RD), African green monkey kidney (Vero), and human embryonic lung diploid fibroblast (KMB17) cells were used to isolate CVA6 from 327 anal swab and fecal samples obtained during HFMD monitoring between 2009 and 2017. The VP1 genes of the isolates were sequenced and genotyped, and the biological characteristics of the representative CVA6 strains were analyzed. A total of 37 CVA6 strains of the D3 gene subtypes were isolated from RD cells, all of which belonged to the epidemic strains in mainland China. Using the adaptive culture method, 10 KMB17 cell-adapted strains were obtained; however, no Vero cell-adapted strains were acquired. Among the KMB17 cell-adapted strains, only KYN-A1205 caused disease or partial death in suckling mice, and its virulence was stronger than its RD cell-adapted strain. The pathogenic KYN-A1205 strain caused strong tropism to the muscle tissue and led to pathological changes, including muscle necrosis and nuclear fragmentation in the forelimb and hindlimb. Sequence analysis demonstrated that the KYN-A1205 strain exhibited multiple amino acid mutations after KMB17 cell adaptation. Moreover, it showed strong pathogenicity, good immunogenicity and genetic stability, and could be used as an experimental CVA6 vaccine candidate. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8418080/ /pubmed/34490141 http://dx.doi.org/10.3389/fcimb.2021.700191 Text en Copyright © 2021 Liu, Zhang, Feng, Cong, Xu, Sun, Yang and Ma 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 Cellular and Infection Microbiology
Liu, Hongbo
Zhang, Ming
Feng, Changzeng
Cong, Shanri
Xu, Danhan
Sun, Hao
Yang, Zhaoqing
Ma, Shaohui
Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease
title Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease
title_full Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease
title_fullStr Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease
title_full_unstemmed Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease
title_short Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease
title_sort characterization of coxsackievirus a6 strains isolated from children with hand, foot, and mouth disease
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418080/
https://www.ncbi.nlm.nih.gov/pubmed/34490141
http://dx.doi.org/10.3389/fcimb.2021.700191
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