This project examines the possible role of the human polyomavirus JC virus (JCV), in perinatal brain infection and tumorigenesis. Initial infection by JCV in childhood is followed by viral latency with reactivation of JCV occurring in the kidney of women during pregnancy. When injected into newborn hamsters, JCV establishes a nonproductive brain infection with subsequent tumor formation. The mechanisms of JCV infection and tumorigenesis and its relevance to human perinatal infection are being explored in three main projects: 1) In JCV-infected neonatal hamsters, immunostaining methods have detected the JCV early region protein, large T-antigen, in mitotically active areas of the brain including the subventricular zone and areas of postnatal granule neuron production. JCV also infects capillary endothelial cells and the level of T-antigen expression in these cells is increased in immunosuppressed hamsters. Focal astrogliosis in the cerebellar internal granular layer accompanies tumor formation and may represent a separate but related pathologic process. 2) Immunostaining and polymerase chain reaction (PCR) techniques are being employed to examine human pediatric tumor specimens. C) The influence of viral regulatory control over T-antigen-induced pathogenesis has been examined in a collaborative project which generated three transgenic mice carrying hybrid JCV-SV40 viral constructs. Pathology exhibited by these mice was variable and suggested a complex relationship between viral regulatory control and tissue-specific induced pathology.
