engleski

MCMV-induced encephalitis in newborn mice : potential role of viral immunoevasion proteins

Congenital human cytomegalovirus (HCMV) infection may result in wide spread encephalitis and developmental abnormalities of the CNS. We have recently established a murine model of CMV encephalitis to study the pathogenesis of HCMV infection in the developing brain. Several proteins encoded by murine CMV (MCMV) are devoted to modulate and evade immune control accomplished trough T- lymphocytes and NK cells. The aim of this study was to identify some of the inflammatory parameters associated with MCMV infection in newborn mice and potential role of viral immunoevasins involved in subversion of CD8+ T cells and NK cell response. Newborn BALB/c mice were injected intraperitoneally with either wild type (w.t.) MCMV or viruses lacking m145, m152 or m155 gene. Animals were sacrificed at various days post infection (p.i.) and their brains were processed for immunohistochemistry. Results revealed infected cells associated with pathohistological lesions scattered throughout the brain parenchyma of mice infected with both w.t. MCMV and deletion mutant viruses. However, the severity of lesions and the number of infected cells were higher in MCMV w.t. infected mice. Infected cells were visible until day 21 p.i., a time when pathohistological lesions were still pronounced. Activated microglia cells within sites of infection and increased expression of proinflammatory cytokines was observed starting from day 8 p.i., followed by infiltration of T lymphocytes. MCMV deletion mutants recruit less lymphocytes, but the proportion of CD4+ and CD8+ cells was similar to MCMV w.t. infected mice with significant prevalence of CD8+ T lymphocytes. Results show that intensity of virus replication in developing brain correlates with the intensity of inflammatory lesions and consequent brain pathology. We concluded that viral immunoevasins for NK and CD8+ T cells play an important role in viral pathogenesis in the CNS of infected mice.

MCMV; encephalitis

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