EFFECT OF 12-OMICRON-TETRADECANOYL-PHORBOL-13-ACETATE ON THE REPLICATION OF EPSTEIN-BARR VIRUS .1. CHARACTERIZATION OF VIRAL-DNA

The tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), induces replication of Epstein-Barr virus (EBV) DNA in a virus-producing human lymphoblastoid cell line, P3HR-1, but not in a nonproducer cell line, Raji. A 6-fold increase in EBV genome copies per P3HR-1 cell parallels the increase in percentage of cells synthesizing viral capsid antigen. In situ cytohybridization with EBV-specific cRNA shows that most of the TPA-treated population participates in the virus-productive cycle. In Raji cells there is abortive induction with an increase in cells showing early antigen from <0.01% to approximately 10%, but there is no increase in EBV genome copies per cell. The optimal TPA concentration for induction of viral DNA replication is 10 ng/ml. EBV DNA synthesized in Raji cells superinfected by virus prepared from TPA-induced P3HR-1 cells is increased approximately 15-fold above that of Raji cells superinfected with control virus. The buoyant density of EBV DNA isolated from virus from TPA-induced cells or of DNA from Raji cells superinfected with TPA-induced and control virus is identical; viral DNA from all sources had the same S value. The XhoI restriction endonuclease digestion patterns of TPA-induced viral DNA and control viral DNA were the same as the viral DNA recovered from Raji cells superinfected with TPA-induced and control virus. Some differences were noted in the molar ratios of some of the fragments. © 1979.