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Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis

Echovirus 11 (E11) is a neurotropic virus that occasionally causes fatal neurological diseases in infected children. However, the molecular mechanism underlying the disease and pathological spectrum of E11 infection remains unclear. Therefore, we modelled E11 infection in 2-day-old type I interferon...

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Autores principales: Zhang, Guoyan, Li, Jichen, Sun, Qiang, Zhang, Keyi, Xu, Wenbo, Zhang, Yong, Wu, Guizhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707869/
https://www.ncbi.nlm.nih.gov/pubmed/34960747
http://dx.doi.org/10.3390/v13122477
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author Zhang, Guoyan
Li, Jichen
Sun, Qiang
Zhang, Keyi
Xu, Wenbo
Zhang, Yong
Wu, Guizhen
author_facet Zhang, Guoyan
Li, Jichen
Sun, Qiang
Zhang, Keyi
Xu, Wenbo
Zhang, Yong
Wu, Guizhen
author_sort Zhang, Guoyan
collection PubMed
description Echovirus 11 (E11) is a neurotropic virus that occasionally causes fatal neurological diseases in infected children. However, the molecular mechanism underlying the disease and pathological spectrum of E11 infection remains unclear. Therefore, we modelled E11 infection in 2-day-old type I interferon receptor knockout (IFNAR−/−) mice, which are susceptible to enteroviruses, with E11, and identified symptoms consistent with the clinical signs observed in human cases. All organs of infected suckling mice were found to show viral replication and pathological changes; the muscle tissue showed the highest viral replication, whereas the brain and muscle tissues showed the most obvious pathological changes. Brain tissues showed oedema and a large number of dead nerve cells; RNA-Seq analysis of the brain and hindlimb muscle tissues revealed differentially expressed genes to be abundantly enriched in immune response-related pathways, with changes in the Guanylate-binding protein (GBP) and MHC class genes, causing aseptic meningitis-related symptoms. Furthermore, human glioma U251 cell was identified as sensitive target cells for E11 infection. Overall, these results provide new insights into the pathogenesis and progress of aseptic meningitis caused by E11.
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spelling pubmed-87078692021-12-25 Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis Zhang, Guoyan Li, Jichen Sun, Qiang Zhang, Keyi Xu, Wenbo Zhang, Yong Wu, Guizhen Viruses Article Echovirus 11 (E11) is a neurotropic virus that occasionally causes fatal neurological diseases in infected children. However, the molecular mechanism underlying the disease and pathological spectrum of E11 infection remains unclear. Therefore, we modelled E11 infection in 2-day-old type I interferon receptor knockout (IFNAR−/−) mice, which are susceptible to enteroviruses, with E11, and identified symptoms consistent with the clinical signs observed in human cases. All organs of infected suckling mice were found to show viral replication and pathological changes; the muscle tissue showed the highest viral replication, whereas the brain and muscle tissues showed the most obvious pathological changes. Brain tissues showed oedema and a large number of dead nerve cells; RNA-Seq analysis of the brain and hindlimb muscle tissues revealed differentially expressed genes to be abundantly enriched in immune response-related pathways, with changes in the Guanylate-binding protein (GBP) and MHC class genes, causing aseptic meningitis-related symptoms. Furthermore, human glioma U251 cell was identified as sensitive target cells for E11 infection. Overall, these results provide new insights into the pathogenesis and progress of aseptic meningitis caused by E11. MDPI 2021-12-10 /pmc/articles/PMC8707869/ /pubmed/34960747 http://dx.doi.org/10.3390/v13122477 Text en © 2021 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
Zhang, Guoyan
Li, Jichen
Sun, Qiang
Zhang, Keyi
Xu, Wenbo
Zhang, Yong
Wu, Guizhen
Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis
title Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis
title_full Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis
title_fullStr Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis
title_full_unstemmed Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis
title_short Pathological Features of Echovirus-11-Associated Brain Damage in Mice Based on RNA-Seq Analysis
title_sort pathological features of echovirus-11-associated brain damage in mice based on rna-seq analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707869/
https://www.ncbi.nlm.nih.gov/pubmed/34960747
http://dx.doi.org/10.3390/v13122477
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