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To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse model to recapitulate human infection by a mosquito bite. A 1\u20135 days postinfection (dpi) study, demonstrated focal viral antigens\/RNA in contralateral thalamic neurons at 3 dpi in 50% of the animals. From 4 to 5 dpi, gradual increase in viral antigens\/RNA was observed in bilateral thalami, somatosensory, and piriform cortices, and then the entire CNS. Infection of neuronal bodies and adjacent nerves in dorsal root ganglia (DRGs), trigeminal ganglia, and autonomic ganglia (intestine, etc.) was also observed from 5 dpi. Infection of explant organotypic whole brain slice cultures demonstrated no viral predilection for the thalamus, while DRG and intestinal ganglia organotypic cultures confirmed sensory and autonomic ganglia susceptibility to infection, respectively. Early thalamus and sensory-associated cortex involvement suggest an important role for sensory pathways in neuroinvasion. Our results suggest that JE virus neuronotropism is much more extensive than previously known, and that the sensory PNS and autonomic system are susceptible to infection.<\/jats:p>","DOI":"10.1093\/jnen\/nlz103","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T12:23:06Z","timestamp":1572610986000},"page":"1160-1170","source":"Crossref","is-referenced-by-count":21,"title":["Japanese Encephalitis Virus Infects the Thalamus Early Followed by Sensory-Associated Cortex and Other Parts of the Central and Peripheral Nervous Systems"],"prefix":"10.1093","volume":"78","author":[{"given":"Tzeh Long","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Pathology; and Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3845-9303","authenticated-orcid":false,"given":"Kien Chai","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Pathology; and Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0368-3268","authenticated-orcid":false,"given":"Soon Hao","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pathology; and Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-4778","authenticated-orcid":false,"given":"Kum Thong","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pathology; and Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,13]]},"reference":[{"key":"2019112009003033300_nlz103-B1","first-page":"435","article-title":"Epidemiology of Japanese encephalitis: Past, present, and future prospects","volume":"11","author":"Wang","year":"2015","journal-title":"Ther Clin Risk Manag"},{"key":"2019112009003033300_nlz103-B2","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2471\/BLT.10.085233","article-title":"Estimated global incidence of Japanese encephalitis: A systematic review","volume":"89","author":"Campbell","year":"2011","journal-title":"Bull World Health Org"},{"key":"2019112009003033300_nlz103-B3","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1056\/NEJMc1701600","article-title":"Autochthonous Japanese encephalitis with yellow fever coinfection in Africa","volume":"376","author":"Simon-Loriere","year":"2017","journal-title":"N Engl J Med"},{"key":"2019112009003033300_nlz103-B4","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.4269\/ajtmh.2012.12-0315","article-title":"Occurrence of Japanese encephalitis virus mosquito vectors in relation to urban pig holdings","volume":"87","author":"Lindahl","year":"2012","journal-title":"Am J Trop Med Hyg"},{"key":"2019112009003033300_nlz103-B5","first-page":"1","article-title":"Clinical profile and outcome of Japanese encephalitis in children admitted with acute encephalitis syndrome","volume":"2013","author":"Kakoti","year":"2013","journal-title":"Biomed Res Int"},{"key":"2019112009003033300_nlz103-B6","first-page":"260","article-title":"Study on Japanese encephalitis virus. 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