MOUSE ADENOVIRUS TYPE-1 REPLICATION IS RESTRICTED TO VASCULAR ENDOTHELIUM IN THE CNS OF SUSCEPTIBLE STRAINS OF MICE

Previous studies have shown that mouse adenovirus type-1 (MAV-1) cause d a fatal hemorrhagic encephalitis in certain strains of mice. C57BI/6 mice exhibited 100% mortality when given as little 10(3) plaque-formi ng units (PFU) of MAV, in contrast to BALB/c mice which were resistant to as many as 10(6) PFU. Susceptible animals died with a flaccid para lysis on the 3rd or 4th day after inoculation. The brains and spinal c ords of these animals displayed numerous petechial hemorrhages that we re found in virtually all areas of the brain, but were more numerous i n white matter. In this paper, immunohistochemistry and electron micro scopy were used to identify the viral target of replication within the CNS of susceptible mice. These studies showed that the CNS vascular e ndothelial cell was the primary site of viral replication within the C NS of mice infected with MAV-1. Characterization of cytokine mRNA leve ls and disease course in immunodeficient mice revealed that the host i mmune response played little, if any, role in the pathogenesis of MAV- 1 disease in susceptible mice and was not responsible for the resistan ce of BALB/c mice. These results support the conclusion that disease c ourse and outcome in susceptible and resistant strains of mice were de termined primarily by the ability of the virus to replicate within the CNS vascular endothelium. (C) 1998 Academic Press.