The study of neuropathogenesis in the developing brain disorders induced by viral infection

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We investigated the effects of murine cytomegalovirus (MCMV) infection on the developing mouse brain in terms of susceptible cells and age-related resistance. Mouse brain slices at different development stages were infected with recombinant MCMV in which the lacZ gene was inserted into a late gene. The ventricular zone (VZ) and cortical marginal region were the sites most susceptible to MCMV infection, and the susceptibility declined with the development of the brain. Immunohistochemical staining showed that the virus-susceptible cells were positive for GFAP, nestin and Musashi-1, suggesting the susceptible cells in the VZ are glial progenitor cells. These results suggest that the amount of immature glial cells in the developing brain may be closely associated with the susceptibility of the brain to CMV infection in humans.We examined the reactivation of latent murine CMV (MCMV) infection in the mouse brain by their transfer to brain slice culture. We infected neonatal and young adult mice intracerebrally with recombinant MCMV. The brains were removed 6 months after infection, and used to prepare brain slices that were then cultured for up to 4 weeks. X-Gal-positive cells were observed in marginal regions of the brains or immature neural cells in the ventricular walls. Immunohistochemical staining showed that the X-Gal-positive reactivated cells were neural stem/progenitor cells. These results suggest that brain disorders may occur long after infection by reactivation of latent infection in the immature neural cells.