Herpes simplex virus type 2 thymidine kinase (HSV-2 TK)

Herpes simplex virus type 2 thymidine kinase (HSV-2 TK) is a viral enzyme encoded by the UL23 gene that is essential for viral DNA replication. It functions by phosphorylating thymidine into thymidine monophosphate, a precursor for DNA synthesis, which is particularly vital during the virus's replication in non-dividing host cells like neurons (UniProt: P06478). The enzyme is a key pharmacological target because it has a significantly broader substrate specificity than human thymidine kinases, allowing it to activate nucleoside analog prodrugs such as acyclovir, valacyclovir, and penciclovir (PubMed: 1654537). These drugs are converted by HSV-2 TK into monophosphate forms, which are then further processed by host kinases into active triphosphates that selectively inhibit viral DNA polymerase and cause DNA chain termination (StatPearls: Antiviral Medications). This mechanism provides a high therapeutic index, as the drugs remain largely inactive in uninfected human cells. However, the clinical utility of targeting HSV-2 TK is often threatened by the development of resistance, typically through mutations in the UL23 gene that result in truncated or non-functional enzymes (PubMed: 11812471). Understanding the structure and function of HSV-2 TK remains crucial for developing next-generation antivirals and managing refractory herpes infections.

Other names

HSV-2 TKUL23Thymidine kinase (HSV-2)ATP:thymidine 5'-phosphotransferase

Phosphorylation of nucleoside analog prodrugs into monophosphate forms, initiating their activation into inhibitors of viral DNA polymerase.