Herpes Simplex Virus Thymidine Kinase (HSV-TK)

Herpes simplex virus thymidine kinase (HSV-TK) is a viral enzyme encoded by the herpes simplex virus. It plays a crucial role in viral DNA replication by phosphorylating thymidine and other nucleoside analogs. Its unique ability to activate prodrugs makes it a valuable target for antiviral therapy and a key component in suicide gene therapy for cancer.

HSV-TK phosphorylates nucleoside analogs (e.g., acyclovir, ganciclovir) into their monophosphate form. Cellular kinases further phosphorylate these to the triphosphate form, which inhibits viral DNA polymerase or acts as a chain terminator during viral DNA synthesis. In gene therapy, HSV-TK converts prodrugs into toxic metabolites, leading to cell death.