Antagonistic action of retinoic acid against teleocidin and 12-O-tetradecanoyl-phorbol-13-acetate on activation of Epstein-Barr virus genomes.

Abstract

Teleocidin, a new potent tumor promoter, produces biological effects similar to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on human lymphoblastoid cell lines. A wide range of concentrations (4-16 ng/ml) of teleocidin were optimal for induction of replication of latent Epstein-Barr virus (EBV) genomes in P3HR-1 cells; cell growth was significantly inhibited in this dose range. In contrast, treatment of Raji cells with an identical dose range of teleocidin did not induce replication of latent EBV genomes. As with TPA, P3HR-1 cells in the stationary phase were twice as responsive to teleocidin induction as exponentially growing cells. The activation of P3HR-1 cells both by teleocidin and TPA greatly enhanced the synthesis of EBV DNA and EBV-associated polypeptides as determined by cRNA - DNA hybridization and by analysis on polyacrylamide gels. Both drugs also increased production of biologically active virus as monitored by the synthesis of viral DNA in superinfected Raji cells. These effects were completely inhibited by retinoic acid. However, retinoic acid did not inhibit the spontaneous viral DNA replication that occurs in P3HR-1 cells not treated with the inducers. Thus, it appears that retinoic acid antagonizes the inducing effects of TPA and teleocidin, but not viral replication itself.