Differential effect of arabinofuranosylthymine of the replication of human herpesviruses

Abstract

The thymidine analog 1-.beta.-arabinofuranosylthymine (ara-T) was previously found to selectively inhibit herpes simplex virus replication. At a relatively nontoxic concentration (50 .mu.g/ml), ara-T reduced herpes simplex virus yields by 4-5 log10. Ara-T was also effective in inhibiting the replication of varicella-zoster virus (VZV) in vitro in human embryo fibroblasts, completely preventing VZV-specific cytopathic effects. The inhibition of VZV was reversible upon drug removal at 48 h after addition but was not reversible after 5 days of treatment. Ara-T also reduced cell-free virus infectivity and the plaque-forming cell yield of VZV. Compared with the untreated controls, which demonstrated a 1-log10 increase over input plaque-forming cells at 24 h after infection, 50 .mu.g of ara-T/ml resulted in a 1-log10 decrease. Unlike herpes simplex virus and VZV, cytomegalovirus replication was relatively resistant to ara-T. Neither cytopathic effects nor the incorporation of [3H]thymidine into acid-insoluble material in cytomegalovirus-infected cells was markedly affected. Analysis of the newly synthesized labeled DNA by CsCl buoyant density determinations indicated that the same relative proportions of cell and virus DNA were synthesized with or without added drug. Interpretation df these results with regard to virus-induced deoxypyrimidine kinase is discussed.