Increased Infectivity of Oncogenic Herpes Viruses of Primates with Tumor Promoter 12-O-Tetradecanoylphorbol-13-Acetate 1

Abstract

Abstract

Cell cultures of simian and human origin infected with two strains each of herpesvirus saimiri (HVS) and herpesvirus ateles (HVA) were compared for production of infectious virus and early and late antigens (EA, LA) in the presence and absence of the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). Second, Epstein-Barr virus (EBV) infected human and simian lymphoblastoid cell lines of high and low cell passages were also compared for enhanced production of early antigen and virus capsid antigen (VCA) using two concentrations of TPA, owl monkey kidney (OMK) and squirrel monkey lung. Cell cultures infected with HVS and HVA with 20 ng/ml of TPA exhibited higher percentages of early and late antigen producing cells and contained 1.0-1.6 logs more virus. Such cells also had earlier cytopathic effects, larger plaques, and a 3-fold increase in the number of plaques. The TPA also enhanced HVS-EA, and LA both in OMK and human skin fibroblast (HSF) cells. The enhancement of EA was approximately 17.0% more in OMK cells and 4.0% more in HSF. The HVS-LA was 22% higher in OMK and 6.0% higher in HSF cells. Pretreatment of OMK cells with TPA prior to HVS or HVA infection showed only a 0.5-0.7 log enhancement of virus. A dose-response of TPA in P₃HRl cells showed that both 20 and 40 ng/ml doses were able to enhance EBV, EA, and VCA significantly with peak enhancement at 40 ng/ml. Higher doses of TPA (60 and 100 ng/ml) resulted in considerable cell death and reduction in antigen production. TPA (20 and 40 ng/ml) stimulated both VCA and EA antigen production in P₃HRl and B95-8 cells, with lesser effects on other human and simian lymphoblastoid cells. However, the stimulation of EA and VCA with these doses of TPA varied for each cell line. Moreover, TPA-treated P₃HRl, B95-8, and 407-I cells on the average also produced 1.0-1.5 logs more virus than the untreated cells. The higher percentage of EA-VCA production from P₃HR1 and B95-8 cells and lower EA-VCA from other human and simian cells suggests that such virus-cell interaction may be influenced by in vitro passages.