Unlike other model tumor virus systems, little is known at the molecular level about any herpesvirus induced oncogenic transformation. Oncogenic transformation of T cells by Herpesvirus saimiri is being studied to elucidate the molecular details of the process by which a normal T cell is converted into an abnormally growing cancer cell. The current studies will expand upon our previous experiments which identified a region of the viral genome that is required for the lymphoma inducing capacity of the virus; this region of the genome is not required for replication of the virus. 1) The protein products derived from this region of the genome in permissively infected cells will be identified and characterized. A small RNA derived from this region of the genome in tumor cell lines and tumor biopsy samples will be mapped, sequenced and characterized. 2) The in vitro transforming ability of wild type Herpesvirus saimiri will be compared to that of a series of mutants with constructed deletions in this region. The design of the deletion derivatives is such that each will be expected to affect the synthesis of only one or two of the four RNAs derived from this region. Changes in the synthesis of RNA and protein products by non-transforming deletion derivatives will be examined. 3) Non-pathogenic strains of Herpesvirus saimiri will be constructed that contain genes for bovine growth hormone and human apo A-1 lipoprotein and that express these genes in vitro and in vaccinated New World primates. These experiments are aimed at demonstrating the utility of herpesvirus vaccines for gene therapy in an animal model.
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