In vitro susceptibility of varicella-zoster virus to acyclovir

The in vitro susceptibility of five strains of varicella-zoster virus to acyclovir was examined by the plaque-reduction method in human diploid lung cells. The 50% effective doses of acyclovir ranged from 2.06 microM to 6.28 microM in a 7-day assay, with a mean of 3.65 microM. Irreversible inhibition of plaque formtation was achieved by drug doses exceeding the 50% effective dose for plaque reduction but nontoxic to the cells. Studies on the relative in vitro susceptibility of varicella-zoster virus and herpes simplex virus types 1 and 2 to acyclovir suggested that varicella-zoster virus is two- to eightfold less susceptible to the drug. The antiviral potency of acyclovir for varicella-zoster virus in vitro was compared with that of several other nucleoside analogs. Analysis of the metabolism of acyclovir in varicella-zoster virus-infected WI-38 cells revealed that, as with herpes simplex virus types 1 and 2, the formation of the triphosphate forms of the drug is specific to viral infection.