Human cytomegalovirus (HCMV), an ubiquitous human pathogen of the herpesvirus family, is responsible for a wide range of human disorders. Studies of HCMV have yielded evidence that infection during pregnancy can result in either mild to severe fetal damage, leading to early death or later manifestations, such as hearing loss, blindness and varying degrees of perceptual, neurologic, psychomotor and behavioral complications as seen in preschool children. The objectives of this study are to elucidate the mechanisms of vertical transmission of cytomegalovius (CMV) and CMV - induced teratogenesis in embryonic development using the mouse as a model system.
The specific aims are, 1) to study the mode(s) vertical transmission murine CMV of (MCMV) and the consequences of infection on fetal development, 2) to study the tissue distribution of MCMV in the developing central nervous system of mouse embryos, and 3) to study the consequences of later-stage MCMV infection on embryogenesis by microinjection of the virus into midgestation mouse embryos. The potential of CMV-infected sperm serving as a vector in vertical transmission of the viral genome to the ovum will be examined by retrieving fertilized eggs from unifected females impregnated with MCMV-infected males transferring the egg to surrogate mothers and studying the consequences of infection during fetal development. Surgical intrauterine inoculation of free virus, as well as reactivation of latent maternal infection during early gestation, as performed in previous studies, support both of these means for generating congenital infections in mice. Resulting organ maldevelopment, especially of the brain will be followed by scanning electron microscopy, conventional histopathology and many other techniques, such as cocultivation assays, nucleic acid hybridization, indirect immunoflurorescence assays and transmission electron microscopy. In other experiments, mouse embryos will be exposed to MCMV by microinjection at midgestation and fetal organogenesis will again be studied using these methods. These studies should provide very valuable information regarding the mechanisms of CMV-attributed implantation failures, fetal maldevelopment; birth defects, mother-to-fetus transmission via the genital tract and vertical CMV transmission via fertilization of ovum with CMV-infected sperm.
| Baskar, J F; Furnari, B; Huang, E S (1993) Demonstration of developmental anomalies in mouse fetuses by transfer of murine cytomegalovirus DNA-injected eggs to surrogate mothers. J Infect Dis 167:1288-95 |
| Baskar, J F; Peacock, J; Sulik, K K et al. (1987) Early-stage developmental abnormalities induced by murine cytomegalovirus. J Infect Dis 155:661-6 |
| Baskar, J F; Stanat, S C; Huang, E S (1986) Murine cytomegalovirus infection of mouse testes. J Virol 57:1149-54 |
| Baskar, J F; Stanat, S C; Huang, E S (1985) Congenital defects due to reactivation of latent murine cytomegaloviral infection during pregnancy. J Infect Dis 152:621-4 |
