The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection

Abstract

Cytomegalovirus (CMV) is the most common infectious cause of congenital anomalies of the brain and also causes brain damage in immunocompromised individuals. We investigated the effects of murine cytomegalovirus (MCMV) infection on the developing mouse brain in terms of susceptible cells and age-related resistance to MCMV in brain slice cultures. Brain slices from BALB/c mice at different developmental stages were infected with recombinant MCMV in which the lacZ gene was inserted into a late gene. The subventricular zone 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, and that most of the infected cells were positive for the proliferative cell nuclear antigen and labeled with bromodeoxyuridine. These results suggest that the susceptible cells in the subventricular zone are immature glial cells, including neural progenitor cells. Immature glial cells proliferated when the brain slices were cultured for a prolonged time and furthermore, they showed themselves to be susceptible to virus infection even under serum-free conditions. These results suggest that the amount of immature glial cells, which include neural progenitor cells, in the developing brain or in the damaged brain with neural proliferation may be closely associated with the susceptibility of the brain to CMV infection in humans.