Blood-brain barrier breakdown and increased intercellular adhesion molecule (ICAM-1/CD54) expression after Semliki Forest (A7) virus infection facilitates the development of experimental allergic encephalomyelitis.
This report describes two mechanisms by which virus infection can facilitate demyelinating autoimmune inflammation in the murine CNS. In the BALB/c mouse model of experimental allergic encephalomyelitis (EAE), peripheral infection with an avirulent strain (A7) of Semliki Forest virus (SFV) increased the morbidity to EAE by infecting endothelial cells and damaging the blood-brain barrier (BBB). An influx of hematogenous CD18+ (LFA-1+ and MAC-1+) cells into the CNS compartment was followed by a local increase in intercellular adhesion molecule 1 (ICAM-1) expression on the vascular endothelium. Although SFV A7 infection without EAE induction caused multifocal cerebral vascular endothelial cell infection and BBB damage followed by cellular infiltration and transient increase of ICAM-1, inflammation and demyelination of CNS white matter with classical clinical signs of EAE was observed only in EAE-induced BALB/c mice, whereas the control mice remained neurologically healthy. The upregulation of ICAM-1 after virus infection was detected after the CD18+ (LFA-1+ and MAC-1+) cells had infiltrated the CNS both after EAE induction and also in nonsensitized control mice. The observed increase in ICAM-1 expression was transient in nonsensitized SFV A7 infected mice just as in the cellular infiltrates in the CNS, but EAE induction resulted in prolongation in both the cellular infiltrates and upregulation of ICAM-1. Thus, SFV A7 infection causes BBB damage and prolongs increased ICAM-1 expression on brain endothelium. This results in increased and more rapid morbidity to EAE in mice which have been sensitized with neuroantigen. However, SFV A7-infected mice without neuroantigen sensitization remain neurologically healthy.
Erälinna
J P
JP
Department of Virology, University of Turku, Finland. juha-pekka.eralinna@utu.fi
Soilu-Hänninen
M
M
Röyttä
M
M
Hukkanen
V
V
Salmi
A A
AA
Salonen
R
R
D018354:Alphavirus Infections; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001812:Blood-Brain Barrier; D018821:CD18 Antigens / Q000032:analysis; D002199:Capillary Permeability; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012672:Semliki forest virus
D000956:Antigens, Viral; D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen