FURTHER CHARACTERIZATION OF THE POTENT AND PROLONGED INHIBITION OF HERPES-SIMPLEX VIRUS-REPLICATION IN HUMAN CELL-LINES BY PENCICLOVIR

The replication of herpes simplex virus type 1 (HSV-1) or HSV-2 in MRC -5 cells infected at 0.01 pfu cell(-1) and treated continuously for 72 h, was inhibited more efficiently by penciclovir than aciclovir (p = 0.0001), However, multiple cycles of replication were required in orde r to distinguish the compounds, Virus from cultures treated for 72 h w ith either compound, at 3 or 10 mu g ml(-1), was resistant to penciclo vir and aciclovir (50% effective concentrations > 10 mu g ml(-1)), but infectivity titres of supernatants from these aciclovir-treated cultu res were higher than for penciclovir. Increased production of resistan t virus in aciclovir-treated cultures may be the consequence of the le ss potent inhibition of virus replication by aciclovir, Penciclovir ca used prolonged inhibition of HSV-1 and HSV-2 replication in three huma n cell lines infected at 1 pfu cell(-1) following treatment for 18 h, whereas virus replication resumed rapidly after withdrawal of aciclovi r, Neither compound showed prolonged activity after 18 h treatment, wh en the multiplicity of infection was reduced to 0.01 pfu cell(-1), Thi s surprising observation prompted experiments testing the effect of re peated pulse treatment in cultures infected at low multiplicity, Penci clovir inhibited HSV-1 replication significantly more effectively than aciclovir in MRC-5 cells infected at 10(-4) pfu cell(-1) and treated daily for 6 h (p < 0.001, n = 5) but only a trend was observed for HSV -2 (p = 0.06, n = 6).