Enhancement of primate retrovirus synthesis by tumour promoters

The tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin were found to be effective in stimulating the synthesis of primate retroviruses in chronically infected human cells. Production of baboon endogenous virus, simian sarcoma virus of woolly monkeys, Mason-Pfizer virus of rhesus monkeys and of a type D isolate from a human cell line was evaluated by assaying particle-associated reverse transcriptase activities in culture fluids of cells grown in the presence or absence of tumour promoters. Both TPA and teleocidin caused a significant but transient increase in virus production, as well as cytomorphological changes in the following infected cell types: human embryonic kidney, Tu 197 human ovarian carcinoma cells, NC 37 human lymphoblastoid line. However, infected A 204 human rhabdomyosarcoma cells were not modified by these promoters. The stimulation of virus production reached its maximum after two to four days, at which time virus production was three to forty times higher than that in controls. The optimal concentration of tumour promoters was 5-10 ng/mL. 12-O-Retinoylphorbol-13-acetate produced a similar but somewhat weaker effect. Control experiments demonstrated that enhancement was specific to those viruses that chronically infected each cell type.