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Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model
Coxsackievirus A6 (CVA6), a member of species A enterovirus, is associated with outbreaks of hand-foot-and-mouth disease and causes a large nationwide burden of disease. However, the molecular pathogenesis of CVA6 remains unclear. In the present study, we established a suckling Institute of Cancer R...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960737/ https://www.ncbi.nlm.nih.gov/pubmed/36851724 http://dx.doi.org/10.3390/v15020511 |
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author | Sun, Qiang Li, Jichen Wang, Rui Sun, Tiantian Zong, Yanjun Wang, Congcong Liu, Ying Li, Xiaoliang Song, Yang Zhang, Yong |
author_facet | Sun, Qiang Li, Jichen Wang, Rui Sun, Tiantian Zong, Yanjun Wang, Congcong Liu, Ying Li, Xiaoliang Song, Yang Zhang, Yong |
author_sort | Sun, Qiang |
collection | PubMed |
description | Coxsackievirus A6 (CVA6), a member of species A enterovirus, is associated with outbreaks of hand-foot-and-mouth disease and causes a large nationwide burden of disease. However, the molecular pathogenesis of CVA6 remains unclear. In the present study, we established a suckling Institute of Cancer Research (ICR) mouse infection model to explore the neural pathogenicity of CVA6. Five-day-old mice infected with CVA6 strain F219 showed lethargy and paralysis, and died 5 or 6 days after infection via IM injection. Cerebral edema and neuronal cell swelling were observed in the infected brain tissue, and we found that the CVA6 VP1 antigen could co-localize with GFAP-positive astrocytes in infected mouse brain using an immunofluorescence assay. CVA6 strain F219 can also infect human glioma (U251) cells. Transcriptome analysis of brain tissues from infected mice and infected U251 cells showed that significantly differentially expressed genes were enriched in antiviral and immune response and neurological system processes. These results indicate that CVA6 could cause neural pathogenesis and provide basic data for exploring the mechanism of how host–cell interactions affect viral replication and pathogenesis. Importance: Coxsackievirus A6 (CVA6) surpasses the two main pathogens, enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16), which are the leading pathogens causing HFMD in many provinces of China. In our study, CVA6 infection caused neurogenic pathogenesis in a neonatal murine model, manifesting as cerebral edema and neuronal cell swelling, CVA6 VP1 antigen could co-localize with GFAP-positive astrocytes in the infected mouse brain. Based on CVA6-infected brain tissue and U251 cell transcriptome analysis, we found upregulated antiviral and immune response-related genes such as Zbp1, Usp18, Oas2, Irf7, Ddx60, Ifit3, Ddx58, and Isg15, while the neurological system process-related genes were downregulated, including Fcrls, Ebnrb, Cdk1, and Anxa5. |
format | Online Article Text |
id | pubmed-9960737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99607372023-02-26 Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model Sun, Qiang Li, Jichen Wang, Rui Sun, Tiantian Zong, Yanjun Wang, Congcong Liu, Ying Li, Xiaoliang Song, Yang Zhang, Yong Viruses Article Coxsackievirus A6 (CVA6), a member of species A enterovirus, is associated with outbreaks of hand-foot-and-mouth disease and causes a large nationwide burden of disease. However, the molecular pathogenesis of CVA6 remains unclear. In the present study, we established a suckling Institute of Cancer Research (ICR) mouse infection model to explore the neural pathogenicity of CVA6. Five-day-old mice infected with CVA6 strain F219 showed lethargy and paralysis, and died 5 or 6 days after infection via IM injection. Cerebral edema and neuronal cell swelling were observed in the infected brain tissue, and we found that the CVA6 VP1 antigen could co-localize with GFAP-positive astrocytes in infected mouse brain using an immunofluorescence assay. CVA6 strain F219 can also infect human glioma (U251) cells. Transcriptome analysis of brain tissues from infected mice and infected U251 cells showed that significantly differentially expressed genes were enriched in antiviral and immune response and neurological system processes. These results indicate that CVA6 could cause neural pathogenesis and provide basic data for exploring the mechanism of how host–cell interactions affect viral replication and pathogenesis. Importance: Coxsackievirus A6 (CVA6) surpasses the two main pathogens, enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16), which are the leading pathogens causing HFMD in many provinces of China. In our study, CVA6 infection caused neurogenic pathogenesis in a neonatal murine model, manifesting as cerebral edema and neuronal cell swelling, CVA6 VP1 antigen could co-localize with GFAP-positive astrocytes in the infected mouse brain. Based on CVA6-infected brain tissue and U251 cell transcriptome analysis, we found upregulated antiviral and immune response-related genes such as Zbp1, Usp18, Oas2, Irf7, Ddx60, Ifit3, Ddx58, and Isg15, while the neurological system process-related genes were downregulated, including Fcrls, Ebnrb, Cdk1, and Anxa5. MDPI 2023-02-12 /pmc/articles/PMC9960737/ /pubmed/36851724 http://dx.doi.org/10.3390/v15020511 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sun, Qiang Li, Jichen Wang, Rui Sun, Tiantian Zong, Yanjun Wang, Congcong Liu, Ying Li, Xiaoliang Song, Yang Zhang, Yong Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model |
title | Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model |
title_full | Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model |
title_fullStr | Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model |
title_full_unstemmed | Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model |
title_short | Coxsackievirus A6 Infection Causes Neurogenic Pathogenesis in a Neonatal Murine Model |
title_sort | coxsackievirus a6 infection causes neurogenic pathogenesis in a neonatal murine model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960737/ https://www.ncbi.nlm.nih.gov/pubmed/36851724 http://dx.doi.org/10.3390/v15020511 |
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