Thymidine kinase from Herpes simplex virus (HSV-TK)

Thymidine kinase from Herpes simplex virus (HSV-TK) is a viral enzyme that catalyzes the phosphorylation of deoxythymidine to thymidine monophosphate in the nucleoside salvage pathway. Unlike human thymidine kinases, HSV-TK exhibits broad substrate specificity, allowing it to phosphorylate not only its natural substrate but also a variety of nucleoside analogues, including antiviral drugs such as acyclovir and ganciclovir. This property underlies its critical role as a target for antiviral therapy and forms the basis for suicide gene therapy in cancer, where HSV-TK is introduced into tumor cells to sensitize them to prodrug treatment. Structurally, HSV-TK is homologous to cellular nucleoside monophosphate kinases but contains distinct peptide segments that modulate its substrate specificity. HSV-TK is considered a non-essential gene for viral replication in dividing cells, but is essential for virulence and replication in non-dividing/specific cell populations, impacting both acute and latent infection dynamics. Its ability to selectively activate prodrugs continues to drive research and development in antiviral, cancer, and gene therapy contexts.

Other names

Herpes simplex virus thymidine kinaseHSV thymidine kinaseHSV-TKTKHSV1

Drug (prodrug) is selectively phosphorylated by HSV-TK to a monophosphate, then further phosphorylated by endogenous kinases to triphosphate. The triphosphate form is then incorporated into DNA, acting as a chain terminator to halt viral DNA synthesis. In suicide gene therapy: Only cells expressing HSV-TK convert ganciclovir and similar prodrugs to the toxic form, selectively killing tumor cells.