Herpesviruses have been implicated in transformation of normal cells to malignant ones, and viral specific macromolecules (DNA, mRNA and proteins) have been detected in many tissues from patients with carcinomas and lymphomas. The purpose of this project is to (1) study the nature and physical state of the viral DNA sequences in malignantly transformed cells and human lymphoblastoid cells; (2) clone the viral DNA sequence(s) responsible for the maintenance of the state of cell transformation and (3) study the role of DNA polymerase and DNA-binding proteins in the viral DNA replication in the transformed cells. A small piece of DNA (approximately 3 x 10 to the 6th power daltons) common to both HSV-1 and HSV-2 has been detected in some lymphoblastoid cells from patients with leukemia. Experiments are now in progress to clone and produce significant amounts of this DNA in E. coli. If successful, we plan to characterize the types of mRNA and proteins this viral DNA can specify in vitro and then use these RNA and protein products to detect viral specific information in lymphoblastoid or other related tissues from patients with leukemia and carcinoma.