509296.fig.001
Figure 1: Schematic diagram of combination therapy approaches in EBV malignancies. EBV maintains latent replication in tumor cells and these tumor cells are not susceptible to anti-herpesvirus prodrugs, such as GCV. In the presence of lytic-phase gene expression-inducing agents such as butyrate, the latent EBV expresses thymidine kinase (TK) which converts the prodrug GCV to GCV-P, which is then converted to the (cytotoxic) triphosphate form by cellular kinases. During DNA replication, the triphosphate form of GCV is then incorporated into genomic and viral DNA, causing chain termination, cell-cycle arrest, and apoptosis of the EBV-infected cells.