Virus-encoded enzyme thymidine kinase

All NRTIs, as exemplified for AZT (Fig. 7), act in a similar fashion following their uptake by the cells, they are phosphorylated successively to their 5 -monophosphate, 5 -diphosphate, and 5 -triphosphate form (De Clercq 2002). Unlike the first phosphorylation step in the metabolic pathway of the acyclic guanosine analogues (see above), which is carried out by a virus-encoded enzyme (thymidine kinase), the first as well as the subsequent phosphorylations of the 2, 3 -dideoxynucleosides are carried out by cellular enzymes, that is, a 2 -deoxynucleoside (e.g., dThd) kinase, a 2 -deoxynucleotide (e.g., dTMP) kinase, and a (2 -deoxy)nucleoside 5 -diphosphate (NDP) kinase. 

Acyclovir is a synthetic purine nucleoside that exhibits in vitro and in vivo inhibition of a nmnber of human viruses. In particular, acyclovir is active against herpes simplex types 1 (HSV-1) and 2 (HSV-2) viruses, varicella zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The inhibitory activity of acyclovir is highly selective. The enzyme thymidine kinase of normal cells does not effectively use acyclovir, but thymidine kinase encoded by one of the viruses noted... 

Chen, M.C. Walker, J. Prusoff, W.H. Kinetic studies of herpes simplex virus type 1-encoded thymidine and thymidylate kinase, a multifunctional enzyme. J. Biol. Chem., 254, 10747-10753 (1979)... 

---