{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T08:04:01Z","timestamp":1788681841439,"version":"build-2803163510"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2016YFD0500407"],"award-info":[{"award-number":["2016YFD0500407"]}]},{"name":"National Key Research and Development Program of China","award":["2016YFD0500407"],"award-info":[{"award-number":["2016YFD0500407"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["32030107"],"award-info":[{"award-number":["32030107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Sciences Foundation of China","doi-asserted-by":"crossref","award":["32030107"],"award-info":[{"award-number":["32030107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>in situ<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0008442","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T13:22:50Z","timestamp":1624281770000},"page":"e0008442","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice"],"prefix":"10.1371","volume":"15","author":[{"given":"Wei","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikai","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanpo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengbo","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-6606","authenticated-orcid":true,"given":"Changqin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"pntd.0008442.ref001","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2471\/BLT.10.085233","article-title":"Estimated global incidence of Japanese encephalitis","volume":"89","author":"G Campbell","year":"2011","journal-title":"Bull World Health Organ"},{"key":"pntd.0008442.ref002","first-page":"171","article-title":"Pathogenesis and clinical features of Japanese encephalitis and West Nile virus infections","volume":"267","author":"T Solomon","year":"2002","journal-title":"Curr Top Microbiol Immunol"},{"key":"pntd.0008442.ref003","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1684\/ecn.2017.0394","article-title":"Skin innate immune response to flaviviral infection","volume":"28","author":"M Garcia","year":"2017","journal-title":"Eur Cytokine Netw"},{"key":"pntd.0008442.ref004","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1046\/j.1523-1747.2000.00904.x","article-title":"Langerhans cells migrate to local lymph nodes following cutaneous infection with an arbovirus","volume":"114","author":"LJ Johnston","year":"2000","journal-title":"J Invest Dermatol"},{"key":"pntd.0008442.ref005","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1007\/s00705-012-1337-4","article-title":"The contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system","volume":"157","author":"DC Clark","year":"2012","journal-title":"Arch virol"},{"key":"pntd.0008442.ref006","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.brainres.2009.02.051","article-title":"Some observations on the tropism of Japanese encephalitis virus in rat brain","volume":"1268","author":"S Kumar","year":"2009","journal-title":"Brain Res"},{"key":"pntd.0008442.ref007","first-page":"219","article-title":"Temporal changes of Japanese encephalitits virus in different brain regions of rat","volume":"138","author":"R Srivastava","year":"2013","journal-title":"Indian J Med Res"},{"key":"pntd.0008442.ref008","first-page":"427","article-title":"In vivo Study on the Japanese Encephalitis: Viral Localization and Histopathology in the Mouse Brain","volume":"36","author":"IB Kim","year":"2003","journal-title":"J. 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