GENE-EXPRESSION OF HERPES-SIMPLEX VIRUS .3. EFFECT OF ARABINOSYLADENINE ON VIRAL POLYPEPTIDE-SYNTHESIS

Arabinosyladenine, an established antiherpetic drug, was used to block herpes simplex virus type 1 (HSV-1) DNA synthesis quantitatively in infected xeroderma pigmentosum (human) cells. Kinetic analyses of viral polypeptides synthesized in the presence and absence of this drug revealed that there were at least 6 distinct kinetic classes of polypeptides. These differed in time of appearance after infection, time of maximum rate of synthesis, kinetics of turnoff and sensitivity to arabinosyladenine. Arabinosyladenine had 3 main effects on HSV1 gene expression. The turnon of immediate early and delayed early polypeptides (kinetic classes 1 and 2) was retarded. The turnoff of early (immediate early and delayed early) polypeptides (classes 1-3) was delayed. The synthesis of late polypeptides (classes 4-6) was inhibited by arabinosyladenine, with class 6 severely (80-90%) inhibited. Viral DNA replication may be required for optimum synthesis of late viral polypeptides.