Herpes simplex virus thymidine kinase (HSV-TK) (HSV-TK)

Herpes simplex virus thymidine kinase (HSV-TK) is a viral enzyme that plays a critical role in the nucleoside salvage pathway by phosphorylating thymidine to thymidine monophosphate, which is essential for viral DNA replication in non-dividing cells [8, 12, 14]. Unlike human thymidine kinases, HSV-TK has a broad substrate specificity, allowing it to phosphorylate various nucleoside analogs such as acyclovir and ganciclovir [15, 20]. The active site of the enzyme contains a deep cleft forming the substrate-binding site, which is the primary target for these antiviral and suicide gene therapy drugs [11, 14]. This property makes it a primary therapeutic target for treating herpes simplex virus infections, as these drugs are selectively activated only in infected cells [6, 10]. Beyond its role in viral infections, HSV-TK is widely utilized in suicide gene therapy for cancer and as a safety switch in cell therapies, where the gene is introduced into target cells to make them susceptible to prodrug-induced death [1, 2, 11]. However, the clinical use of HSV-TK can be limited by the emergence of drug-resistant mutations and the potential immunogenicity of the viral protein in human patients [1, 14, 21].

Other names

HSV1-TKHSV2-TKHHV-1 TKHHV-2 TKThymidine kinase (viral)Deoxypyrimidine kinaseDeoxythymidine kinase

HSV-TK selectively phosphorylates nucleoside analogs (prodrugs) into monophosphates. Host cell kinases then convert these into triphosphates, which compete with natural dGTP for incorporation into DNA by DNA polymerase, leading to DNA chain termination and inhibition of DNA synthesis [6, 8, 9, 11, 17].