UC Irvine

Studies were performed to investigate the contributions of the CC chemokine receptor CCR5 in host defense and disease development following intracranial infection with mouse hepatitis virus (MHV). T cell recruitment was impaired in MHV-infected CCR5(-/-) mice at day 7 postinfection (pi), which correlated with increased (P < or = 0.03) titers within the brain. However, by day 12 pi, T cell infiltration into the CNS of infected CCR5(-/-) and CCR5(+/+) mice was similar and both strains exhibited comparable viral titers, indicating that CCR5 expression is not essential for host defense. Following MHV infection of CCR5(+/+) mice, greater than 50% of cells expressing CCR5 antigen were activated macrophage/microglia (determined by F4/80 antigen expression). In addition, infected CCR5(-/-) mice exhibited reduced (P < or = 0.02) macrophage (CD45(high)F4/80(+)) infiltration, which correlated with a significant reduction (P < or = 0.001) in the severity of demyelination compared to CCR5(+/+) mice. These data indicate that CCR5 contributes to MHV-induced demyelination by allowing macrophages to traffic into the CNS.