[Murine cytomegalovirus for the animal models of congenital cytomegalovirus infection in human]

Abstract

Cytomegalovirus(CMV) is the most common infectious cause of congenital anomalies of the central nervous system(CNS) caused by intrauterine infection in humans. Since studies of human subjects have obvious limitation and CMV have strict species specificity, we have developed model systems for brain abnormalities induced by infection of mouse embryos with murine CMV (MCMV) which has similarities in structure and biology to human CMV (HCMV). We have previously reported that brain abnormalities, such as microphthalmia and brain atrophy, can be induced in mouse embryo by injection MCMV in to the conceptus at mid gestation. We have also showed that neurotropic feature of MCMV are prominent and that viral antigens in neuronal cells are also observed for a prolonged time following infection. We showed the evidences which suggest that MCMV may persistently infect in neuronal cells, whereas lytic infection may preferentially occur in glial cell in the developing brain. Disturbance of the neuronal migration and loss of neurons were reported to occur postnatally in the brains of MCMV-infected mice. Furthermore, MCMV infection induces apoptosis in uninfected neurons, and blocks and induction of apoptosis of primary neuronal cultures. These viral effect on the induction and blocking neuronal apoptosis, resulting in persistent infection, may be important for pathogenesis of morphological and functional brain disorders caused by congenital CMV infection in humans.