The mechanism by which DNA tumor viruses transform mammalian cells is our primary investigative interest. Taking advantage of cellular systems that in vitro undergo normal differentiation, we have studied the human epithelial cell infection by SV40 and papillomaviruses. An important feature of the latter viral group is their histotypical site of infection, i.e., different viral prototypes can infect and produce lesion in vivo only in different types of stratified epithelia. Some prototypes are associated in vivo only with benign growth, whereas others are associated with carcinomas, particularly cervical carcinomas. Thus, each lesion's outcome must depend on the interaction of specific cellular factors with certain viral genes or their products.

To analyze the interplay of these various components, we use different approaches: 1) developing in vitro systems of cultured human epithelial cells to study the conditions that determine viral replication versus integration; 2) identifying cellular factors and viral sequences that determine the specificity of the cell type-virus interaction; 3) identifying proto-oncogenes or their products which cooperate with the viral genes in the progression of the transformation process; 4) identifying and characterizing viral genome products that act in transformation and their mechanistic action at the molecular and cellular levels; and 5) studying changes in structural components of the transformed cells, such as keratins and other specific differentiation products, and of the mechanisms regulating these changes.