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Passive immunization prevents MCMV-induced pathology in the CNS of newborn mice

Human cytomegalovirus (HCMV) infection of the central nervous system (CNS) is the most frequent cause of congenital abnormalities that include learning disabilities, microcephaly and hearing loss. The pathogenesis of the CNS infection is still insufficiently defined, and may arise upon direct damage of CMV-infected neurons or indirectly, due to inflammatory response to infection. We used a recently established model of murine CMV (MCMV) infection in newborn mice (Koontz T. et al. J. Exp. Med. 2008) to analyze the contribution of humoral immunity to virus clearance from the brain. In brains of MCMV-infected newborn mice treated with immune serum virus titer was reduced below detection limit as compared to brains of mice receiving control (non-immune) serum where significant amounts of virus were recovered. Treatment with MCMV specific monoclonal antibodies also resulted in the reduction of virus titer in the brain. Histopathological analyses revealed significantly less CNS inflammation in mice treated with immune serum or monoclonal antibodies as compared to recipients of control serum or irrelevant antibodies which had marked mononuclear cell infiltrates and prominent glial nodules in the brain parenchyma. Antiviral antibodies were also effective in preventing virus associated developmental abnormalities in MCMV-infected newborn brain in terms of improved neuronal migration and increased cerebellar area as compared to control mice. In conclusion, our data indicate that virus specific antibodies have a protective role in the development of CNS pathology in MCMV infected newborn mice, suggesting that antiviral antibodies are an important component of immunological responses during CMV infection of developing CNS.

MCMV immunization newborn mice

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