EFFECT OF BV-ARAU AND ACYCLOVIR ON VARICELLA-ZOSTER VIRUS-REPLICATIONWITH VARIOUS LENGTH AND TIMING OF DRUG EXPOSURE

We studied antiviral effects of 1-beta-D-arabinofluranosyl-5[(E)-2-bro movinyl] uracil (BV-araU) and acyclovir against varicella-zoster virus (VZV) multiplication varying the length or timing of drug exposure. F irst, residual anti-VZV effect of drugs, exposed to cells for various periods followed by incubation in drug-free medium, was determined by the plaque inhibition assay. None of the drugs showed activity when re moved within 24 hr of incubation. Weakened efficacy of BV-araU was see n in 2 days of treatment. When it was removed after 3 or 4 days, the E D(50) was as low as that for cultures in which the drug was not remove d. Still, plaque inhibition was not complete even at high concentratio ns. Acyclovir inhibited plaque formation only by 50% or less in 2 days of treatment. It gave a much higher ED(50) in 3 days of treatment tha n that observed without drug removal. In the experiments, in which BV- araU was added to VZV-infected cells 1 day after infection, BV-araU im mediately suppressed increase in the number of infective centers at a concentration of 0.001 mu g/ml, and reduced it at concentrations of 0. 01 mu g/ml or higher. The reduction of infective centers was seen with a dose-dependent manner when added 2 or 3 days after infection. BV-ar aU stimulated the decrease in the number of infective centers when add ed 4 days after infection. This inhibitory effect of acyclovir was ver y weak. Microscopic observations supported the above results. BV-araU was still much superior to acyclovir in the anti-VZV effect when the l ength and timing of drug exposure were varied.