{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:32:14Z","timestamp":1787319134632,"version":"build-2736575974"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Hepatitis E virus (HEV) is increasingly recognized as a cause of neurological disease beyond its hepatic manifestations. Neurological complications are the most frequently reported extrahepatic presentations and include both peripheral nervous system disorders, such as Guillain\u2013Barr\u00e9 syndrome (GBS) and neuralgic amyotrophy (NA), and central nervous system (CNS) involvement, including encephalitis and myelitis, often in the absence of overt hepatitis. This review summarizes the clinical spectrum of HEV-associated neurological disease and integrates evidence from human studies and experimental models. Current evidence supports multifactorial pathogenesis, with direct viral neuroinvasion of the CNS and immune-mediated mechanisms predominating in peripheral neuropathies. Experimental\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    systems demonstrate that HEV can cross the blood\u2013brain barrier (BBB) and replicate within neural tissues, providing biological plausibility for CNS involvement. By synthesizing clinical and experimental findings, this review highlights the dual pathogenic pathways underlying HEV-associated neurological injury and outlines key unresolved questions relevant to diagnosis, pathogenesis, and clinical management.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1810452","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:49:34Z","timestamp":1776836974000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatitis E virus-associated neurological injury and neurotropic cellular mechanisms"],"prefix":"10.3389","volume":"16","author":[{"given":"Zixuan","family":"Guo","sequence":"first","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewei","family":"Tian","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Development Center of Science and Technology, Beijing Municipal Bureau of Agriculture and Rural Affairs","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Yin","sequence":"additional","affiliation":[{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, NHC Key Laboratory of Medical Virology and Viral Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubing","family":"Ou","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlong","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"She","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijing","family":"Tian","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology and Public Health, State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.3390\/vaccines9101205","article-title":"Hepatitis E virus quasispecies in cerebrospinal fluid with neurological manifestations","volume":"9","author":"Abravanel","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.jinf.2018.06.007","article-title":"Acute hepatitis E in French patients and neurological manifestations","volume":"77","author":"Abravanel","year":"2018","journal-title":"J. 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