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Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route

Enterovirus A71 (EV-A71) is a major etiological agent of human hand, foot and mouth disease, and it can cause severe neurological complications. Although several genotypes of EV-A71 strains are prevalent in different regions of the world, the genotype C4 has circulated in mainland China for more tha...

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Autores principales: Zhu, Junping, Chen, Ning, Zhou, Shuya, Zheng, Kai, Sun, Lin, Zhang, Yuxiao, Cao, Lina, Zhang, Xiaoyan, Xiang, Qiaoyan, Chen, Zhiyun, Wang, Chenfei, Fan, Changfa, He, Qiushui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281673/
https://www.ncbi.nlm.nih.gov/pubmed/30518755
http://dx.doi.org/10.1038/s41426-018-0201-3
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author Zhu, Junping
Chen, Ning
Zhou, Shuya
Zheng, Kai
Sun, Lin
Zhang, Yuxiao
Cao, Lina
Zhang, Xiaoyan
Xiang, Qiaoyan
Chen, Zhiyun
Wang, Chenfei
Fan, Changfa
He, Qiushui
author_facet Zhu, Junping
Chen, Ning
Zhou, Shuya
Zheng, Kai
Sun, Lin
Zhang, Yuxiao
Cao, Lina
Zhang, Xiaoyan
Xiang, Qiaoyan
Chen, Zhiyun
Wang, Chenfei
Fan, Changfa
He, Qiushui
author_sort Zhu, Junping
collection PubMed
description Enterovirus A71 (EV-A71) is a major etiological agent of human hand, foot and mouth disease, and it can cause severe neurological complications. Although several genotypes of EV-A71 strains are prevalent in different regions of the world, the genotype C4 has circulated in mainland China for more than 20 years. The pathogenicity of different EV-A71 clinical isolates varies and needs to be explored. In this study, hSCARB2 knock-in mice (N = 181) with a wide range of ages were tested for their susceptibility to two EV-A71 strains with the subgenotypes C4 and C2, and two infection routes (intracranial and venous) were compared. The clinical manifestations and pathology and their relationship to the measured viral loads in different tissues were monitored. We observed that 3 weeks is a crucial age, as mice younger than 3-week-old that were infected became extremely ill. However, mice older than 3 weeks displayed diverse clinical symptoms. Significant differences were observed in the pathogenicity of the two strains with respect to clinical signs, disease incidence, survival rate, and body weight change. We concluded that hSCARB2 knock-in mice are a sensitive model for investigating the clinical outcomes resulting from infection by different EV-A71 strains. The intracranial infection model appears to be suitable for evaluating EV-A71 neurovirulence, whereas the venous infection model is appropriate for studying the pathogenicity of EV-A71.
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spelling pubmed-62816732018-12-10 Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route Zhu, Junping Chen, Ning Zhou, Shuya Zheng, Kai Sun, Lin Zhang, Yuxiao Cao, Lina Zhang, Xiaoyan Xiang, Qiaoyan Chen, Zhiyun Wang, Chenfei Fan, Changfa He, Qiushui Emerg Microbes Infect Article Enterovirus A71 (EV-A71) is a major etiological agent of human hand, foot and mouth disease, and it can cause severe neurological complications. Although several genotypes of EV-A71 strains are prevalent in different regions of the world, the genotype C4 has circulated in mainland China for more than 20 years. The pathogenicity of different EV-A71 clinical isolates varies and needs to be explored. In this study, hSCARB2 knock-in mice (N = 181) with a wide range of ages were tested for their susceptibility to two EV-A71 strains with the subgenotypes C4 and C2, and two infection routes (intracranial and venous) were compared. The clinical manifestations and pathology and their relationship to the measured viral loads in different tissues were monitored. We observed that 3 weeks is a crucial age, as mice younger than 3-week-old that were infected became extremely ill. However, mice older than 3 weeks displayed diverse clinical symptoms. Significant differences were observed in the pathogenicity of the two strains with respect to clinical signs, disease incidence, survival rate, and body weight change. We concluded that hSCARB2 knock-in mice are a sensitive model for investigating the clinical outcomes resulting from infection by different EV-A71 strains. The intracranial infection model appears to be suitable for evaluating EV-A71 neurovirulence, whereas the venous infection model is appropriate for studying the pathogenicity of EV-A71. Nature Publishing Group UK 2018-12-05 /pmc/articles/PMC6281673/ /pubmed/30518755 http://dx.doi.org/10.1038/s41426-018-0201-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhu, Junping
Chen, Ning
Zhou, Shuya
Zheng, Kai
Sun, Lin
Zhang, Yuxiao
Cao, Lina
Zhang, Xiaoyan
Xiang, Qiaoyan
Chen, Zhiyun
Wang, Chenfei
Fan, Changfa
He, Qiushui
Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route
title Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route
title_full Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route
title_fullStr Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route
title_full_unstemmed Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route
title_short Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route
title_sort severity of enterovirus a71 infection in a human scarb2 knock-in mouse model is dependent on infectious strain and route
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281673/
https://www.ncbi.nlm.nih.gov/pubmed/30518755
http://dx.doi.org/10.1038/s41426-018-0201-3
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