DNA synthesis inhibitors suppress expression of Epstein-Barr virus in chemically activated human lymphoblastoid cells

Of the DNA synthesis inhibitors tested, novobiocin, nalidixic acid, coumermycin A1, mitomycin C, hydroxyurea, and bleomycin effectively inhibited Epstein-Barr virus (EBV)-related early antigen (EA) synthesis induced in human lymphoblastoid cells by 12-O-tetradecanoyl-phorbol-13-acetate and n-butyrate, but did not inhibit EA synthesis in 12-O-tetradecanoyl-phorbol-13-acetate and n-butyrate, but did not inhibit EA synthesis in cells superinfected with EBV. Inhibition of EA synthesis by treatment with novobiocin, nalidixic acid, or coumermycin A1 paralleled that of total cellular DNA synthesis, whereas mitomycin C, hydroxyurea, and bleomycin prevented EA synthesis at higher concentrations than those required for DNA inhibition. Inhibition of EA and total RNA synthesis was not in parallel. The inhibition by novobiocin, nalidixic acid, bleomycin, and hydroxyurea was reversible. Our results suggest that DNA synthesis inhibitors prevent the synthesis of EA in a manner independent of their inhibitory effects on cellular DNA synthesis and that these inhibitors act on a common process of EBV genome activation by different inducing agents.