DIFFERENTIAL EXPRESSION OF THE IMMEDIATE-EARLY AND EARLY ANTIGENS IN NEURONAL AND GLIAL-CELLS OF DEVELOPING MOUSE BRAINS INFECTED WITH MURINE CYTOMEGALOVIRUS

Brain disorders induced by congenital cytomegalovirus (CMV) infection may appear at a later time after birth as a consequence of persistent infection and/or the activation of a latent infection of the neural ce lls. We have analyzed the infection dynamics of the neural cells in th e neonatal mouse brains infected with murine CMV (MCMV) in the late st age of gestation. First we prepared a rat monoclonal antibody to the m ajor immediate-early (IE)-89K antigen and then used the antibody for c omparison of the expression of early and late viral genes in the devel oping mouse brains. The cells expressing the IE-89K antigen were mostl y localized in the ventricular and subventricular zones and were prefe rentially double stained with anti-glial fibrillary acidic protein and anti-nestin antibodies. In contrast, the cells expressing the early n uclear antigen, detected by the monoclonal antibody D5, were diffusely distributed in the cortex and the hippocampus and were mostly double labelled with anti-neuron-specific enolase antibody. In neonatal mouse brains infected congenitally with recombinant MCMV, which expressed l acZ as a late gene, the number of the early nuclear antigen-positive c ells was much higher than that of the beta-galactosidase-expressing ce lls, the number of which was almost the same as that of the IE-89K ant igen-positive cells. In addition, the distribution of viral DNA-rich c ells detected by DNA-DNA hybridization was similar to that of the IE-8 9K antigen-positive cells. These results suggest that CMV may persiste ntly infect neuronal cells, whereas lyric infection may preferentially occur in the glial cells in the developing brain.