INHIBITION OF HERPES-SIMPLEX VIRUS-INDUCED DNA-POLYMERASE ACTIVITY AND VIRAL-DNA REPLICATION BY 9-(2-HYDROXYETHOXYMETHYL)GUANINE AND ITS TRIPHOSPHATE

The effect of the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) on herpes simplex virus type 1 DNA synthesis was examined. Acycloguanosine inhibited herpesvirus DNA synthesis in virus-infected cells [human cervical carcinoma HeLa, African green monkey kidney Vero]. The synthesis of host cell DNA was only partially inhibited in actively growing cells at acycloguanosine concentrations several hundred-fold greater than the 50% effective dose for herpes simplex virus type 1. Studies using partially purified enzymes revealed that the triphosphate of this compound inhibited the virus-induced DNA polymerases (DNA nucleotidyltransferases) to a greater degree than the .alpha.-DNA polymerase of the host cell; that the inhibition was dependent upon the base composition of the template and that the triphosphate was a better substrate for the virus-induced polymerases than for the .alpha.-cellular DNA polymerases.