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Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination

Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children’s health. However, compared with enterovir...

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Autores principales: Ji, Wangquan, Qin, Luwei, Tao, Ling, Zhu, Peiyu, Liang, Ruonan, Zhou, Guangyuan, Chen, Shuaiyin, Zhang, Weiguo, Yang, Haiyan, Duan, Guangcai, Jin, Yuefei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192712/
https://www.ncbi.nlm.nih.gov/pubmed/34122374
http://dx.doi.org/10.3389/fmicb.2021.658093
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author Ji, Wangquan
Qin, Luwei
Tao, Ling
Zhu, Peiyu
Liang, Ruonan
Zhou, Guangyuan
Chen, Shuaiyin
Zhang, Weiguo
Yang, Haiyan
Duan, Guangcai
Jin, Yuefei
author_facet Ji, Wangquan
Qin, Luwei
Tao, Ling
Zhu, Peiyu
Liang, Ruonan
Zhou, Guangyuan
Chen, Shuaiyin
Zhang, Weiguo
Yang, Haiyan
Duan, Guangcai
Jin, Yuefei
author_sort Ji, Wangquan
collection PubMed
description Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children’s health. However, compared with enterovirus 71 detected frequently in fatal cases, limited attention has been paid to CVA2 infections because of its benign clinical course. In the present study, we identified three CVA2 strains from HFMD infections and used the cell-adapted CVA2 strain HN202009 to inoculate 5-day-old BALB/c mice intramuscularly. These mice developed remarkably neurological symptoms such as ataxia, hind-limb paralysis, and death. Histopathological determination showed neuronophagia, pulmonary hemorrhage, myofiberlysis and viral myocarditis. Viral replication was detected in multiple organs and tissues, and CVA2 exhibited strong tropism to muscle tissue. The severity of illness was associated with abnormally high levels of inflammatory cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor α, and monocyte chemotactic protein 1, although the blockade of these proinflammatory cytokines had no obvious protection. We also tested whether an experimental formaldehyde-inactivated CVA2 vaccine could induce protective immune response in adult mice. The CVA2 antisera from the vaccinated mice were effective against CVA2 infection. Moreover, the inactivated CVA2 vaccine could successfully generate immune protection in neonatal mice. Our results indicated that the neonatal mouse model could be a useful tool to study CVA2 infection and to develop CVA2 vaccines.
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spelling pubmed-81927122021-06-12 Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination Ji, Wangquan Qin, Luwei Tao, Ling Zhu, Peiyu Liang, Ruonan Zhou, Guangyuan Chen, Shuaiyin Zhang, Weiguo Yang, Haiyan Duan, Guangcai Jin, Yuefei Front Microbiol Microbiology Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children’s health. However, compared with enterovirus 71 detected frequently in fatal cases, limited attention has been paid to CVA2 infections because of its benign clinical course. In the present study, we identified three CVA2 strains from HFMD infections and used the cell-adapted CVA2 strain HN202009 to inoculate 5-day-old BALB/c mice intramuscularly. These mice developed remarkably neurological symptoms such as ataxia, hind-limb paralysis, and death. Histopathological determination showed neuronophagia, pulmonary hemorrhage, myofiberlysis and viral myocarditis. Viral replication was detected in multiple organs and tissues, and CVA2 exhibited strong tropism to muscle tissue. The severity of illness was associated with abnormally high levels of inflammatory cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor α, and monocyte chemotactic protein 1, although the blockade of these proinflammatory cytokines had no obvious protection. We also tested whether an experimental formaldehyde-inactivated CVA2 vaccine could induce protective immune response in adult mice. The CVA2 antisera from the vaccinated mice were effective against CVA2 infection. Moreover, the inactivated CVA2 vaccine could successfully generate immune protection in neonatal mice. Our results indicated that the neonatal mouse model could be a useful tool to study CVA2 infection and to develop CVA2 vaccines. Frontiers Media S.A. 2021-05-28 /pmc/articles/PMC8192712/ /pubmed/34122374 http://dx.doi.org/10.3389/fmicb.2021.658093 Text en Copyright © 2021 Ji, Qin, Tao, Zhu, Liang, Zhou, Chen, Zhang, Yang, Duan and Jin. 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
Ji, Wangquan
Qin, Luwei
Tao, Ling
Zhu, Peiyu
Liang, Ruonan
Zhou, Guangyuan
Chen, Shuaiyin
Zhang, Weiguo
Yang, Haiyan
Duan, Guangcai
Jin, Yuefei
Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination
title Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination
title_full Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination
title_fullStr Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination
title_full_unstemmed Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination
title_short Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination
title_sort neonatal murine model of coxsackievirus a2 infection for the evaluation of antiviral therapeutics and vaccination
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192712/
https://www.ncbi.nlm.nih.gov/pubmed/34122374
http://dx.doi.org/10.3389/fmicb.2021.658093
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