Epstein–Barr virus thymidine kinase (EBV-TK) (EBV-TK)

Epstein–Barr virus thymidine kinase (EBV-TK), encoded by the BXLF1 gene, is a viral enzyme essential for the salvage pathway of deoxyribonucleotide synthesis during the lytic phase of the viral life cycle [2, 5]. Unlike the broad-spectrum thymidine kinase of herpes simplex virus (HSV-TK), EBV-TK exhibits a narrower substrate specificity, primarily phosphorylating thymidine and certain analogs like brivudine and zidovudine [5, 9]. It is a critical target in "cytolytic virus activation" (CLVA) or "kick and kill" therapeutic strategies, where pharmacological agents such as HDAC inhibitors or butyrate are used to induce the lytic cycle and EBV-TK expression in latently infected tumor cells [1, 6]. Once induced, EBV-TK monophosphorylates nucleoside prodrugs, which are then converted by host kinases into active triphosphates that inhibit viral DNA polymerase and trigger apoptosis [4, 16]. This strategy is particularly relevant for treating EBV-associated malignancies, including nasopharyngeal carcinoma, Burkitt lymphoma, and post-transplant lymphoproliferative disorders, where the virus typically evades standard therapy by remaining in a latent state [1, 11, 19].

Other names

BXLF1Epstein-Barr virus thymidine kinaseHHV-4 thymidine kinaseDeoxypyrimidine kinase

EBV-TK acts as a prodrug-activating enzyme that monophosphorylates specific nucleoside analogs. These monophosphates are subsequently converted into active triphosphate forms by cellular kinases, which then inhibit viral DNA polymerase and cause DNA chain termination [4, 5, 9].