title: Semliki Forest virus infects mouse brain endothelial cells and causes blood-brain barrier damage.
abstract: Induction of experimental allergic encephalomyelitis is facilitated in a genetically resistant BALB/c mouse strain by a nonpathogenic strain of a neurotropic alphavirus, Semliki Forest virus (SFV-A7). One possible explanation for this enhancement is virus infection of endothelial cells (EC), causing increased permeability of the blood-brain barrier. We have now sought evidence for virus infection of EC in vivo by immunocytochemistry and in situ hybridization. SFV-A7 antigens and RNA were detected in vascular EC and perivascular neurons in cerebellar and spinal cord white matter. Expression of viral antigens was followed by fibrinogen leakage from the blood vessels into brain parenchyma. This was shown by immunoperoxidase staining detecting fibrinogen extravascularly in central nervous system sections of infected mice. Simultaneously, expression of ICAM-1 (intercellular adhesion molecule 1) was induced on brain EC. SFV-A7 replicated in mouse brain microvascular EC in vitro and caused lysis of the cells. SFV-A7 did not induce ICAM-1 expression of mouse brain microvascular EC in vitro, while ICAM-1 was readily induced by gamma interferon and interleukin 1 beta. The observed increase of ICAM-1 expression on EC is immune mediated and not a direct effect of the virus infection. We conclude that SFV-A7 infection causes cerebral microvascular damage which contributes to the facilitation of experimental allergic encephalomyelitis in BALB/c mice.
authors.affiliation: Department of Virology, University of Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Soilu-Hänninen
authors.forename: J P
authors.initials: JP
authors.lastname: Erälinna
authors.forename: V
authors.initials: V
authors.lastname: Hukkanen
authors.forename: M
authors.initials: M
authors.lastname: Röyttä
authors.forename: A A
authors.initials: AA
authors.lastname: Salmi
authors.forename: R
authors.initials: R
authors.lastname: Salonen
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001812:Blood-Brain Barrier; D001921:Brain / Q000382:microbiology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000382:microbiology*; D012367:RNA, Viral / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis; D012672:Semliki forest virus / Q000472:pathogenicity*
chemical_list: D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D012367:RNA, Viral; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen