The goal of this project is to examine the possible role of the human polyomavirus, JC virus (JCV) in perinatal brain infection. Childhood acquisition of JCV is followed by viral latency and reactivation of JCV in the kidney with shedding of virus occurring during pregnancy and the postpartum period. When injected intracerebrally into newborn hamsters, JCV establishes a nonproductive brain infection with subsequent tumor formation. The implications of this for human perinatal infection are being explored through three main projects: a) Studies utilizing the hamster model have revealed that JCV preferentially infects mitotic cells in the subventricular zone and sites of postnatal granule neuron production in the developing brain. Further investigation has suggested that JCV infection of blood vessel endothelial cells and local astrogliosis may be involved in the mechanisms of tumor induction. Tumors induced in 6 -month old hamsters exhibit variable expression of JCV early protein product, T-antigen, emphasizing that the virus is not readily detected in the cells it transforms. b) Preliminary studies examining human pediatric tumor tissue for the presence of JCV or its T-antigen are being performed using immunostaining and PCR techniques. c) In collaboration with Dr. Prakash, 4 transgenic mice have been produced that carry the hybrid regulatory and coding early regions from JCV and SV40. Observed pathology included an abdominal lymphoma and adrenal tumor in one mouse, a choroid plexus papilloma in a second mouse and a brainstem tumor in a third animal. Splenic, thymic and epidermal abnormalities were also noted.
