Effect of acyclovir on herpes simplex virus replication in a persistently infected human lymphoblastoid cell line (P3HR-1)

Abstract

We examined the effect of acyclovir on herpes simplex virus (HSV) replication in the persistently infected human lymphoblastoid cell line, P3HR-1. During 10 days of continuous exposure of P3HR-1 cells to 100 μ M acyclovir there was a decrease in the number of cells expressing HSV antigens, the number of copies of HSV DNA per cell, and the infectivity of extracellular virus. A significant increase in each of these was detected after 14 days of continuous exposure of P3HR-1 cells to the drug, demonstrating that the replication of HSV has become resistant to inhibition by acyclovir. No apparent resistance of EBV replication to inhibition by acyclovir, however, was detected in HSV-infected P3HR-1 cells. The number of copies per cell of EBV and HSV DNA increased after exposure of HSV-infected P3HR-1 cells to the tumor promoter TPA (12-O-tetradecanoyl-phorbol-13-acetate). When cells were exposed continuously to acyclovir for four months and then exposed to acyclovir and TPA simultaneously, the number of copies per cell of HSV DNA increased, but the number of copies per cell of EBV DNA increased by only a few, if any. The detection in P3HR-1 cultures of individual cells expressing both HSV and EBV antigens suggested that HSV and EBV productive cycles could occur simultaneously within the same cell. However, single cells very rarely expressed both antigens simultaneously.