title: A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model.
abstract: Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, beta-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation.
authors.affiliation: Division of Medical Microbiology, University of Liverpool, Liverpool, UK.
authors.forename: Allison C
authors.initials: AC
authors.lastname: German
authors.forename: Khin Saw Aye
authors.initials: KS
authors.lastname: Myint
authors.forename: Nguyen Thi Hoang
authors.initials: NT
authors.lastname: Mai
authors.forename: Ian
authors.initials: I
authors.lastname: Pomeroy
authors.forename: Nguyen Hoan
authors.initials: NH
authors.lastname: Phu
authors.forename: John
authors.initials: J
authors.lastname: Tzartos
authors.forename: Peter
authors.initials: P
authors.lastname: Winter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Collett
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Alan
authors.initials: A
authors.lastname: Barrett
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.forename: Tom
authors.initials: T
authors.lastname: Solomon
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000956:Antigens, Viral / Q000097:blood; D001253:Astrocytes / Q000473:pathology; D002648:Child; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D004672:Encephalitis, Japanese / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008854:Microscopy, Electron
chemical_list: D000956:Antigens, Viral