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However, HEV infection has been recently associated with a wide spectrum of extrahepatic manifestations, particularly neurological disorders. Previous studies have shown that HEV is able to cross the blood\u2013brain barrier (BBB) and induce inflammatory response of the central nervous system. However, the pathogenesis of HEV\u2010induced neuroinflammation and tissue injury of the central nervous system have yet to be fully elucidated. In this study, activation of NLRP3 inflammasome following HEV infection were investigated. In a gerbil model infected by HEV, brain histopathological changes including gliosis, neuronophagia and neuron injury were observed and expression of NLRP3, caspase\u20101, IL\u20101\u03b2 and IL\u201018 were elevated. Brain microvascular endothelial cells (BMECs) are key components of the BBB that protects the brain from various challenges. Following HEV infection, virus\u2010like particles range from 30 to 40\u2009nm in diameter were observed in human BMECs (hBMECs). Enhanced expression levels of NLRP3 and subsequent ASC, caspase\u20101, IL\u20101\u03b2 and IL\u201018 were detected in infected cells. Treatment with MCC950 alleviated HEV infection induced activation of NLRP3 inflammasome, mitochondrial damage and VE\u2010cadherin degradation. The findings provide new insights into HEV\u2010associated neuroinflammation. Moreover, targeting NLRP3 inflammasome signalling is a promising therapeutic in HEV\u2010induced neurological disorder.<\/jats:p>","DOI":"10.1111\/jvh.13998","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T05:42:07Z","timestamp":1723527727000},"page":"729-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>NLRP3<\/scp>\n                    Inflammasome Activation Mediates Hepatitis E Virus\u2010Induced Neuroinflammation"],"prefix":"10.1111","volume":"31","author":[{"given":"Bingyan","family":"Wei","sequence":"first","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huopeng","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory 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