Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.

Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse...

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Autores principales: Wei Han, Mingxing Gao, Changqing Xie, Jinhua Zhang, Zikai Zhao, Xueying Hu, Wanpo Zhang, Xiaoli Liu, Shengbo Cao, Guofu Cheng, Changqin Gu
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:851d18505d9a4834bfd0aebd380837c12021-11-25T06:31:45ZPrecise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.1935-27271935-273510.1371/journal.pntd.0008442https://doaj.org/article/851d18505d9a4834bfd0aebd380837c12021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0008442https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse model was established using a highly virulent P3 strain of JEV. Immunohistochemistry and in situ hybridization, combined with anatomical imaging of the mouse brain, were used to dynamically localize the virus and construct three-dimensional (3D) images. Consequently, onset of mild clinical signs occurred in some mice at 3.5 d post JEV infection, while most mice displayed typical neurological signs at 6 d post-infection (dpi). Moreover, brain pathology revealed typical changes associated with non-suppurative encephalitis, which lasted up to 8 d. The earliest detection of viral antigen was achieved at 3 dpi in the thalamus and medulla oblongata. At 6 dpi, the positive viral antigen signals were mainly distributed in the cerebral cortex, olfactory area, basal ganglia, thalamus, and brainstem regions in mice. At 8 dpi, the antigen signals gradually decreased, and the localization of JEV tended to concentrate in the cerebrum and thalamus, while no viral antigen was detected in the brain at 21 dpi. In this model, the viral antigen was first expressed in the reticular thalamic nucleus (Rt), and the virus content is relatively stable. The expression of the viral antigen in the hippocampal CA2 region, the anterior olfactory nucleus, and the deep mesencephalic nucleus was high and persistent. The 3D images showed that viral signals were mostly concentrated in the parietal cortex, occipital lobe, and hippocampus, near the mid-sagittal plane. In the early stages of infection in mice, a large number of viral antigens were detected in denatured and necrotic neurons, suggesting that JEV directly causes neuronal damage. From the time of its entry, JEV is widely distributed in the central nervous system thereby causing extensive damage.Wei HanMingxing GaoChangqing XieJinhua ZhangZikai ZhaoXueying HuWanpo ZhangXiaoli LiuShengbo CaoGuofu ChengChangqin GuPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0008442 (2021)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Wei Han
Mingxing Gao
Changqing Xie
Jinhua Zhang
Zikai Zhao
Xueying Hu
Wanpo Zhang
Xiaoli Liu
Shengbo Cao
Guofu Cheng
Changqin Gu
Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.
description Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse model was established using a highly virulent P3 strain of JEV. Immunohistochemistry and in situ hybridization, combined with anatomical imaging of the mouse brain, were used to dynamically localize the virus and construct three-dimensional (3D) images. Consequently, onset of mild clinical signs occurred in some mice at 3.5 d post JEV infection, while most mice displayed typical neurological signs at 6 d post-infection (dpi). Moreover, brain pathology revealed typical changes associated with non-suppurative encephalitis, which lasted up to 8 d. The earliest detection of viral antigen was achieved at 3 dpi in the thalamus and medulla oblongata. At 6 dpi, the positive viral antigen signals were mainly distributed in the cerebral cortex, olfactory area, basal ganglia, thalamus, and brainstem regions in mice. At 8 dpi, the antigen signals gradually decreased, and the localization of JEV tended to concentrate in the cerebrum and thalamus, while no viral antigen was detected in the brain at 21 dpi. In this model, the viral antigen was first expressed in the reticular thalamic nucleus (Rt), and the virus content is relatively stable. The expression of the viral antigen in the hippocampal CA2 region, the anterior olfactory nucleus, and the deep mesencephalic nucleus was high and persistent. The 3D images showed that viral signals were mostly concentrated in the parietal cortex, occipital lobe, and hippocampus, near the mid-sagittal plane. In the early stages of infection in mice, a large number of viral antigens were detected in denatured and necrotic neurons, suggesting that JEV directly causes neuronal damage. From the time of its entry, JEV is widely distributed in the central nervous system thereby causing extensive damage.
format article
author Wei Han
Mingxing Gao
Changqing Xie
Jinhua Zhang
Zikai Zhao
Xueying Hu
Wanpo Zhang
Xiaoli Liu
Shengbo Cao
Guofu Cheng
Changqin Gu
author_facet Wei Han
Mingxing Gao
Changqing Xie
Jinhua Zhang
Zikai Zhao
Xueying Hu
Wanpo Zhang
Xiaoli Liu
Shengbo Cao
Guofu Cheng
Changqin Gu
author_sort Wei Han
title Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.
title_short Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.
title_full Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.
title_fullStr Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.
title_full_unstemmed Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice.
title_sort precise localization and dynamic distribution of japanese encephalitis virus in the rain nuclei of infected mice.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/851d18505d9a4834bfd0aebd380837c1
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