Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis
Human parechovirus type 3 (PeV-A3) infection has been recognized as an emerging etiologic factor causing severe nerve disease or sepsis in infants and young children. But the neuropathogenic mechanisms of PeV-A3 remain unknown. To understand the pathogenesis of PeV-A3 infection in the neuronal syste...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:2b8c417aad7f48fb99cf8a71a04fcdc72021-11-30T21:33:07ZCharacterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis1664-322410.3389/fimmu.2021.753683https://doaj.org/article/2b8c417aad7f48fb99cf8a71a04fcdc72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.753683/fullhttps://doaj.org/toc/1664-3224Human parechovirus type 3 (PeV-A3) infection has been recognized as an emerging etiologic factor causing severe nerve disease or sepsis in infants and young children. But the neuropathogenic mechanisms of PeV-A3 remain unknown. To understand the pathogenesis of PeV-A3 infection in the neuronal system, PeV-A3-mediated cytopathic effects were analyzed in human glioblastoma cells and neuroblastoma cells. PeV-A3 induced interferons and inflammatory cytokine expression in these neuronal cells. The pronounced cytopathic effects accompanied with activation of death signaling pathways of apoptosis, autophagy, and pyroptosis were detected. A new experimental disease model of parechovirus encephalitis was established. In the disease model, intracranial inoculation with PeV-A3 in C57BL/6 neonatal mice showed body weight loss, hindlimb paralysis, and approximately 20% mortality. PeV-A3 infection in the hippocampus and cortex regions of the neonatal mouse brain was revealed. Mechanistic assay supported the in vitro results, indicating detection of PeV-A3 replication, inflammatory cytokine expression, and death signaling transduction in mouse brain tissues. These in vitro and in vivo studies revealed that the activation of death signaling and inflammation responses is involved in PeV-A3-mediated neurological disorders. The present results might account for some of the PeV-A3-associated clinical manifestations.Ming-Wei JanMing-Wei JanHong-Lin SuTsung-Hsien ChangKuen-Jer TsaiKuen-Jer TsaiFrontiers Media S.A.articleparechovirus A3cytopathic effectinflammationneuronal diseasesinfectious modelImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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parechovirus A3 cytopathic effect inflammation neuronal diseases infectious model Immunologic diseases. Allergy RC581-607 |
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parechovirus A3 cytopathic effect inflammation neuronal diseases infectious model Immunologic diseases. Allergy RC581-607 Ming-Wei Jan Ming-Wei Jan Hong-Lin Su Tsung-Hsien Chang Kuen-Jer Tsai Kuen-Jer Tsai Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis |
description |
Human parechovirus type 3 (PeV-A3) infection has been recognized as an emerging etiologic factor causing severe nerve disease or sepsis in infants and young children. But the neuropathogenic mechanisms of PeV-A3 remain unknown. To understand the pathogenesis of PeV-A3 infection in the neuronal system, PeV-A3-mediated cytopathic effects were analyzed in human glioblastoma cells and neuroblastoma cells. PeV-A3 induced interferons and inflammatory cytokine expression in these neuronal cells. The pronounced cytopathic effects accompanied with activation of death signaling pathways of apoptosis, autophagy, and pyroptosis were detected. A new experimental disease model of parechovirus encephalitis was established. In the disease model, intracranial inoculation with PeV-A3 in C57BL/6 neonatal mice showed body weight loss, hindlimb paralysis, and approximately 20% mortality. PeV-A3 infection in the hippocampus and cortex regions of the neonatal mouse brain was revealed. Mechanistic assay supported the in vitro results, indicating detection of PeV-A3 replication, inflammatory cytokine expression, and death signaling transduction in mouse brain tissues. These in vitro and in vivo studies revealed that the activation of death signaling and inflammation responses is involved in PeV-A3-mediated neurological disorders. The present results might account for some of the PeV-A3-associated clinical manifestations. |
format |
article |
author |
Ming-Wei Jan Ming-Wei Jan Hong-Lin Su Tsung-Hsien Chang Kuen-Jer Tsai Kuen-Jer Tsai |
author_facet |
Ming-Wei Jan Ming-Wei Jan Hong-Lin Su Tsung-Hsien Chang Kuen-Jer Tsai Kuen-Jer Tsai |
author_sort |
Ming-Wei Jan |
title |
Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis |
title_short |
Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis |
title_full |
Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis |
title_fullStr |
Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis |
title_full_unstemmed |
Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis |
title_sort |
characterization of pathogenesis and inflammatory responses to experimental parechovirus encephalitis |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/2b8c417aad7f48fb99cf8a71a04fcdc7 |
work_keys_str_mv |
AT mingweijan characterizationofpathogenesisandinflammatoryresponsestoexperimentalparechovirusencephalitis AT mingweijan characterizationofpathogenesisandinflammatoryresponsestoexperimentalparechovirusencephalitis AT honglinsu characterizationofpathogenesisandinflammatoryresponsestoexperimentalparechovirusencephalitis AT tsunghsienchang characterizationofpathogenesisandinflammatoryresponsestoexperimentalparechovirusencephalitis AT kuenjertsai characterizationofpathogenesisandinflammatoryresponsestoexperimentalparechovirusencephalitis AT kuenjertsai characterizationofpathogenesisandinflammatoryresponsestoexperimentalparechovirusencephalitis |
_version_ |
1718406251258314752 |