Herpes simplex virus type 1 thymidine kinase (HSV-1 TK) (HSV-1 TK)

Herpes simplex virus type 1 thymidine kinase (HSV-1 TK) is a viral enzyme essential for the synthesis of viral DNA, particularly in non-dividing cells where cellular deoxyribonucleotide pools are low (UniProt: P03176). It functions by phosphorylating thymidine to thymidine monophosphate, but it possesses a significantly broader substrate specificity than its mammalian counterparts, allowing it to accept various nucleoside analogs (PubMed: 16233487). This unique property makes it the primary target for anti-herpetic drugs like acyclovir and ganciclovir, which serve as prodrugs selectively activated by the viral enzyme (StatPearls: NBK542155). Once phosphorylated, these drugs inhibit viral DNA polymerase, effectively halting viral replication. In addition to its role in treating infections, HSV-1 TK is a cornerstone of suicide gene therapy in oncology, where the gene is introduced into tumor cells to sensitize them to ganciclovir-mediated cell death (PubMed: 10449389). However, mutations in the UL23 gene encoding HSV-1 TK are a major driver of clinical drug resistance, particularly in immunocompromised individuals (PubMed: 23935149).

Other names

HSV1-TKUL23Thymidine kinase (HSV-1)ATP:thymidine 5'-phosphotransferase

The enzyme acts as a nucleoside kinase that phosphorylates specific nucleoside analogs (prodrugs) into their monophosphate forms. These intermediates are subsequently converted by host cellular kinases into triphosphate forms, which act as competitive inhibitors of viral DNA polymerase and cause DNA chain termination (StatPearls: NBK542155).