PROLONGED INFECTION OF MOUSE-BRAIN NEURONS WITH MURINE CYTOMEGALOVIRUS AFTER PRENATAL AND PERINATAL INFECTION

The susceptibility of mice at different developmental stages to a rela tively low titer of cell culture-passaged murine cytomegalovirus (MCMV ) infection was compared in terms of the urinary excretion of MCMV exa mined by plaque assay and in terms of the distribution of viral infect ion, determined by immunohistochemistry, using antibodies specific to the early nuclear antigen of MCMV. Viral infection on day 8.5 of gesta tion (E8.5) into the conceptus and intraperitoneal infection on day 15 .5 of gestation (E15.5), postnatal day 2 (P2), postnatal day 11 (P11), and 30 days after birth (P30), respectively, were performed. Embryona l and perinatal mice were more susceptible to MCMV in terms of urinary excretion of the virus and the presence of viral antigen-positive cel ls in the brain, lungs, and kidneys. In the embryonal and perinatal in fection, the viral antigen-positive cells in the neurons of the cerebr al cortex and hippocampus were retained late after birth, even though the positive cells in the lungs and kidneys had disappeared. In the mi ce infected on E8.5, small clusters of viral antigen-positive cells we re detected only in the cortex and hippocampus late after birth, witho ut the urinary excretion of virus. These results suggest that when mic e are infected with MCMV at the embryonal and perinatal stages, elimin ation of the infected neurons is delayed compared with that of the oth er cells in the lungs and kidneys. These findings provide a model for the analysis of pathogenesis of the subclinical congenital CMV infecti on that manifested clinically late after birth in humans as brain diso rders.