On the basis of the work done in the first grant period with acyclovir (ACV) and Epstein-Barr Virus (EBV) we have constructed a project extending this work and consisting of two parts: the first describes experiments designed to evaluate and characterize virologically and biologically the effects of four promising new antiviral agents (B10LF-62, BVDU, FIAC and FMAU), all nucleoside analogs and one of them a congener of ACV, on EBV replication both in isolated nuclei and in cell culture systems. The second part deals with the mode of action of the drugs. In this part based on what we have learned from our studies with ACV we will investigate drug metabolism and purify and characterize EBV-specified DNA polymerase, a key enzyme in the drug interactions, with respect to (i) kinetics of inhibition by phosphorylated drug, (ii) the ability of drug-triphosphates to serve as substrate, (iii) effect of incubation on primer-template efficiency, (iv) question of chain termination, (v) identification of incorporated drug moieties in EBV DNA, and (vi) reversibility of drug effects correlated with impact on latent infection. Data obtained from these studies will facilitate our understanding of the molecular mechanisms of action of the drugs and help in the development of selective antiviral agents.