SEMLIKI-FOREST VIRUS INFECTS MOUSE-BRAIN ENDOTHELIAL-CELLS AND CAUSESBLOOD-BRAIN-BARRIER DAMAGE

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 possi ble 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 imm unocytochemistry and in situ hybridization. SFV-A7 antigens and RNA we re 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 extravasc ularly in central nervous system sections of infected mice. Simultaneo usly, expression of ICAM-1 (intercellular adhesion molecule 1) was ind uced 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 exp ression of mouse brain microvascular EC in vitro, while ICAM-1 was rea dily induced by gamma interferon and interleukin Ip. The observed incr ease of ICAM-1 expression on EC is immune mediated and not a direct ef fect 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.