A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4

Summary: Coxsackievirus A4 (CVA4) as a pathogen causing severe herpangina has become global outbreak epidemics during the past 5 years. However, there is currently no effective vaccines and drugs available. Here, one mouse-adapted CVA4 virus (YZ08) was cultivated by repeatedly cross-passaging betwee...

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Main Authors: Qin Su, Xiao Chen, Zhihui Zheng, Hailin Wei, Jiaxue Zhou, Libing Zhang, Ali Muhammad, Yin Wang, Xiang Chen, Pinghu Zhang
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225012830
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author Qin Su
Xiao Chen
Zhihui Zheng
Hailin Wei
Jiaxue Zhou
Libing Zhang
Ali Muhammad
Yin Wang
Xiang Chen
Pinghu Zhang
author_facet Qin Su
Xiao Chen
Zhihui Zheng
Hailin Wei
Jiaxue Zhou
Libing Zhang
Ali Muhammad
Yin Wang
Xiang Chen
Pinghu Zhang
author_sort Qin Su
collection DOAJ
description Summary: Coxsackievirus A4 (CVA4) as a pathogen causing severe herpangina has become global outbreak epidemics during the past 5 years. However, there is currently no effective vaccines and drugs available. Here, one mouse-adapted CVA4 virus (YZ08) was cultivated by repeatedly cross-passaging between human RD cells and 11-day-old juvenile mice. Our results revealed the YZ08 virus was highly lethal to 13-day-old juvenile mice. Virus titer assay indicated that the YZ08 virus effectively replicated in juvenile mice. This model was successfully used to evaluate the therapeutic efficacy of herb medicine, anti-CVA4 rabbit sera, and antiviral drugs. Our results indicated that all tested reagents effectively provided protection for CVA4 virus infection by prolonging survival time, promoting survival, and preventing weight loss. Collectively, we successfully established a juvenile mouse model of CVA4 virus, which was a powerful tool for investigating the pathogenesis of CVA4 or evaluating the efficacy of antiviral reagents or vaccines.
format Article
id doaj-art-d906a82328484da4afdb122d8d81feba
institution DOAJ
issn 2589-0042
language English
publishDate 2025-08-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-d906a82328484da4afdb122d8d81feba2025-08-20T03:08:17ZengElsevieriScience2589-00422025-08-0128811302210.1016/j.isci.2025.113022A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4Qin Su0Xiao Chen1Zhihui Zheng2Hailin Wei3Jiaxue Zhou4Libing Zhang5Ali Muhammad6Yin Wang7Xiang Chen8Pinghu Zhang9Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225009, ChinaEmergency Intensive Care Unit (EICU) and Department of Emergency Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225002, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225009, China; National Human Diseases Animal Model Resource Center, NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Science and Peking Union Medical School, Beijing 100021 ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225009, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225009, ChinaEmergency Intensive Care Unit (EICU) and Department of Emergency Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225002, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225009, ChinaYangzhou Center for Disease Control and Prevention, The Affiliated CDC of Yangzhou University, Yangzhou 225001, China; Corresponding authorJiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Corresponding authorJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Corresponding authorSummary: Coxsackievirus A4 (CVA4) as a pathogen causing severe herpangina has become global outbreak epidemics during the past 5 years. However, there is currently no effective vaccines and drugs available. Here, one mouse-adapted CVA4 virus (YZ08) was cultivated by repeatedly cross-passaging between human RD cells and 11-day-old juvenile mice. Our results revealed the YZ08 virus was highly lethal to 13-day-old juvenile mice. Virus titer assay indicated that the YZ08 virus effectively replicated in juvenile mice. This model was successfully used to evaluate the therapeutic efficacy of herb medicine, anti-CVA4 rabbit sera, and antiviral drugs. Our results indicated that all tested reagents effectively provided protection for CVA4 virus infection by prolonging survival time, promoting survival, and preventing weight loss. Collectively, we successfully established a juvenile mouse model of CVA4 virus, which was a powerful tool for investigating the pathogenesis of CVA4 or evaluating the efficacy of antiviral reagents or vaccines.http://www.sciencedirect.com/science/article/pii/S2589004225012830pharmacologymicrobiologyvirology
spellingShingle Qin Su
Xiao Chen
Zhihui Zheng
Hailin Wei
Jiaxue Zhou
Libing Zhang
Ali Muhammad
Yin Wang
Xiang Chen
Pinghu Zhang
A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4
iScience
pharmacology
microbiology
virology
title A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4
title_full A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4
title_fullStr A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4
title_full_unstemmed A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4
title_short A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4
title_sort lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus a4
topic pharmacology
microbiology
virology
url http://www.sciencedirect.com/science/article/pii/S2589004225012830
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