engleski

MCMV induced encephalitis and developmental brain disorders in newborn mice

Problem: Congenital human cytomegalovirus (HCMV) infection of the central nervous system (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 CNS we have developed a model of perinatal CMV infection of the CNS by infecting newborn mice with murine CMV (MCMV). Method of study: Mice were infected intraperitoneally (ip) 6– 12 h after birth then sacrificed at various days post infection (p.i.). Their brains were processed for immunohistochemical and Flow cytometry analysis. Results: MCMV readily infects different cell types in developing mouse brain including neurons and glial cells. Parallel with visible infection, we observed 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 lymphocytees represent the dominant immune population within 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. Conclusions: Intraperitoneal MCMV infection of newborn mice results in a multi-focal encephalitis tied with delays in postnatal cerebellar development. The observed increase in mononuclear cell infiltration suggests that virus clearance is mediated by activated immune cells recruited from the periphery.

MCMV Encephalitis Developmantal Brain Disorder

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