SWITCHING VIRAL LATENCY TO VIRAL LYSIS - A NOVEL THERAPEUTIC APPROACHFOR EPSTEIN-BARR VIRUS-ASSOCIATED NEOPLASIA

We describe an EBV-driven lytic system (LySED) that can be used to spe cifically target therapy to EBV-containing tumors. This system takes a dvantage of the transactivating properties of EBNA-1, a latency protei n expressed in all EBV-containing cells, to drive the expression of Zt a, a gene sufficient for inducing the EBV lytic cycle. Thus, EBV provi des both the target and the executor for mediating tumor-specific cell death, markedly increasing the specificity of the system. Transfectio n of EBV-positive cell lines with the LySED construct resulted in a sw itch to lytic cycle and subsequent cell death, even in the presence of an inhibitor of EBV thymidine kinase (acyclovir) without an increase in virion production. In contrast, growth of EBV-negative B-cell lines was not affected.