The study of virus-induced brain disorders by a model system using neural stem cells

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Cytomegalovirus (CMV) is the most frequent infectious cause of development disorders of the brain in humans. Infection of the neural stem/progenitor cells (NSPCs) seems to be primarily responsible for the generation of the brain abnormalities. Previously, we reported that NSPCs prepared from fetal mouse brains were permissive for murine CMV (MCMV) infection, and that the virus infection suppressed their growth and migration, and inhibited their differentiation, especially neuronal differentiation (Lab Invest 2000). However, it needs to be elucidated how viral genes cause the disorder of NSPCs during MCMV infection. In this study we tried to establish a model system for investigating the effects of MCMV genes on the growth and differentiation of NSPCs. An immediate early 1 (ie1) gene was transduced into NSPCs via a retrovirus vector. The transduction of ie1 suppressed the growth of NSPCs. When NSPCs were induced to differentiate, in the ie1-transduced NSPCs the expression of microtubules-associated protein 5 (MAP5), an early neuronal marker, was decreased as compared with control. These data suggest that MCMV IE1 protein disrupts the ability of self-renewal and multi-potency which are the principal functions of NSPCs. The transduction of viral genes into NSPCs might provide a model system for clarifying the pathogenesis of the brain abnormalities in congenital CMV infection in humans.