The long term objective of this research is to elucidate cellular and viral factors which determine the oncogenicity of BK virus. Sequences within the BK virus enhancer will be defined with respect to their importance for gene expression, DNA replication and transformation. Cellular factors which interact with these sequences will be identified, and the mechanism of gene control by the enhancer analyzed. We will determine whether there is a correlation between expression of the early region and development of pathology in transgenic mice. Using cells transformed in culture, and tumor cells obtained from transgenic mice, we will study the mechanisms by which the BK virus tumor antigens induce transformation. We will determine the cellular localization of the BK tumor antigens, and determine whether they associate with known cellular growth regulators at those sites. We will measure the extent of complex formation with p53 and other cellular proteins.