engleski

MCMV-induced encephalitis in newborn mice

Congenital human cytomegalovirus (HCMV) infection of the CNS is the leading viral cause of mental retardation and progressive hearing loss. In order to study the pathogenesis of congenital HCMV infection within developing central nervous system (CNS) we developed a small animal model of perinatal CMV infection of the CNS by infecting newborn mice with murine CMV (MCMV). Mice were infected intraperitoneally (ip) 6-12 h after birth then sacrificed at various days post infection (p.i.). Our results show that MCMV readily infects the brains of newborn mice. We also confirmed that different cell types in the brain parenchyma are permissive for MCMV infection, including neurons and glial cells. Parallel with visible infection, we found deficits in postnatal cerebellar morphogenesis in terms of delayed granule neuron migration and disruptions in Purkinje cell morphology. We have also defined the phenotype of immune cells infiltrating the infected CNS. NK cells can be detected in the brain parenchyma within the first week p.i., while macrophages and T lymphocytes predominate from day 12 p.i.. CD8+ T lymphocytes represent the dominant population of immune cells within the infected CNS and MHC tetramer staining reveals that a significant amount of these cells is MCMV specific. Increased expression of CD28, a co-stimulatory molecule present on effector CD8+ T cells, implies these cells have an activated phenotype. Overall, our data shows that intraperitoneal infection of newborn mice with MCMV results in multi-focal encephalitis coupled with delays in postnatal cerebellar maturation. The observed increase in mononuclear cell infiltration suggests that virus clearance is mediated by activated immune cells recruited from the periphery.

MCMV encephalitis brain newborn

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