Differential chemokine induction by the mouse adenovirus type-1 in the central nervous system of susceptible and resistant strains of mice

Mouse adenovirus-type 1 (MAV-1) has recently been shown to cause a fatal he morrhagic encephalopathy in certain strains of mice whereas other strains a re resistant, Morbidity is associated with a productive infection of cerebr ovascular endothelial cells, resulting in necrosis of the vasculature, infa rction, hemorrhage and death within 4 - 6 days. Previous studies were not a ble to define a role for the innate or acquired immune response. In the cur rent study we have addressed the effect of MAV-1 on chemokine and chemokine receptor expression in the central nervous system (CNS) and spleen of susc eptible (C57BL/6) and resistant (BALB/c) strains of mice. Intra-peritoneal infection with MAV-1 in C57BL/6 animals resulted in early and prominent ind uction of IP-10/crg-2 in the spleen and CNS. Increased expression of MCP-1, MIP-1 alpha, MIP-1 beta and RANTES was also noted in the CNS of MAV-1-infe cted C57BL/6 animals commencing around 72 h post-infection, In contrast, ch emokine expression in BALB/c animals was more restricted with prominent upr egulation only of MIP-2 in the CNS. In situ hybridization identified the va scular endothelium and CNS glia as the principal site of IP-10/crg-2 produc tion in the C57BL/6 animals. The chemokine receptors CCR1-5 were upregulate d in the CNS of both strains of mice. These data show that productive infec tion of the CNS with MAV-1 leads to the upregulation of a characteristic pa ttern of chemokines and their receptors, which may point to a role for thes e factors in disease pathogenesis.