engleski

Innate Immune Response And Developmental Abnormalities In Murine Cytomegalovirus Infected Newborn Brain

Congenital human cytomegalovirus (HCMV) infection is a leading viral cause of hearing loss and severe motor deficits. In order to study the pathogenesis of this infection we have established a model of perinatal murine CMV (MCMV) infection by inoculating the virus intraperitoneally into newborn mice. Together with productive infection we readily observed developmental abnormalities of newborn brain in terms of delayed migration of neurons, impaired morphology of Purkinje cells and decreased cerebellar area as compared to uninfected mice. These developmental abnormalities were symmetric and global in nature and did not coincide with visible loci of infection. This finding led us to hypothesize that soluble molecular mediators of immune response to MCMV might underpin these histological abnormalities. We detected robust inflammatory response in infected brain comprising the increased expression of proinflammatory chemokines and activation of innate immune response. NK cells infiltrate into infected CNS already within the first week post infection (p.i.), while macrophages predominate starting from day 12 p.i. We also analyzed the impact of MCMV infection on expression of a central nervous system (CNS) patterning transcription factor HOXa5. HOXa5 protein expression was decreased by approximately 40% in developing cerebellum and vestibular nuclei. Possible functional consequence of this decrease in vestibule-nuclear HOXa5 expression is manifested as a reduction in a performance on a balance beam behavioral assessment in adult infected mice.

MCMV Innate immune response; Developmental abnormalities; brain newborn

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