THE EFFECT OF METABOLIC INHIBITORS ON THE LARGE PLAQUE EFFECT WITH HERPES SIMPLEX VIRUS

Abstract— Herpes simplex virus (HSV) macroplaque strain plaque development is faster on ultraviolet (UV)-irradiated African green monkey kidney cells if viral infection is delayed for 12 h or more after cell irradiation (Coohill et al. , 1980). This phenomenon has been termed the large plaque effect (LPE). Here we show that treatment of UV-irradiated cells with cycloheximide inhibits the LPE. Pretreatment of unirradiated cells with hydroxyurea, caffeine, or acetoxy-acetylaminofluorene results in faster plaque development. Treatment of UV-irradiated cells with either hydroxyurea or caffeine gave a LPE of the same magnitude as UV alone. In addition, the LPE was observed with other HSV strains—microplaque, syn-20, and KOS. Our results are consistent with the interpretation that the LPE is 'inducible' in African green monkey kidney cells and that inhibition of DNA synthesis is the inducing event. Possible causes of the LPE and similarities between the LPE and enhanced viral reactivation are discussed.