Epstein-Barr virus thymidine kinase (EBV-TK)

Epstein-Barr virus thymidine kinase (EBV-TK) is a viral enzyme encoded by the BXLF1 gene that plays a pivotal role in the salvage pathway of deoxyribonucleotide synthesis by phosphorylating thymidine (UniProt: P03179). Unlike human thymidine kinase, EBV-TK has the unique ability to phosphorylate certain nucleoside analogs, such as ganciclovir and acyclovir, converting them into monophosphate forms that are eventually processed into toxic triphosphates by cellular kinases (PubMed: 10823893). This enzymatic activity is the basis for the pharmacological treatment of EBV infections and is exploited in suicide gene therapy strategies for EBV-associated cancers like nasopharyngeal carcinoma and post-transplant lymphoproliferative disorders (PubMed: 16254654). In these therapeutic contexts, the expression of EBV-TK is often induced or targeted to tumor cells to facilitate selective cell death upon administration of a prodrug (PubMed: 21835905). Although EBV-TK is less efficient at processing some purine analogs compared to the Herpes Simplex Virus thymidine kinase, it remains a primary target for developing specific antiviral agents and diagnostic tools for monitoring EBV lytic activation (PubMed: 15141013).

Other names

BXLF1Thymidine kinase (EBV)Epstein-Barr virus BXLF1 proteinEBV-associated thymidine kinase

The enzyme acts as a nucleoside kinase that selectively phosphorylates nucleoside analog prodrugs into their monophosphate forms. These intermediates are subsequently converted by host cellular kinases into triphosphate derivatives, which act as competitive inhibitors of viral DNA polymerase and cause DNA chain termination, leading to cell death or inhibition of viral replication.