Effect of indomethacin on Epstein-Barr virus early antigen induction

The lymphoid cell line, Raji, was derived from a Burkitt's lymphoma and is readily inducible for Epstein-Barr virus (EBV) early antigen synthesis by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Treatment of Raji and other EBV genome-positive cells with indomethacin caused a marked inhibition of early antigen induction by 12-O-tetradecanoylphorbol-13-acetate and other chemical inducers. However, this effect did not appear to be due to inhibition of prostaglandin synthesis since the concentration of indomethacin required to inhibit EBV-early antigen induction was 50- to 100-fold higher than that normally required for the inhibition of prostaglandin synthesis. In addition, no prostaglandin synthesis was detected in 12-O-tetradecanoylphorbol-13-acetate-treated Raji cells. EBV-early antigen induction by superinfection was resistant to inhibition by indomethacin and indicates that induction by chemical inducers and by super-infection follows different pathways. Indomethacin at the concentrations required to inhibit EBV-early antigen induction also was cytostatic, which indicates that the cell cycle phase may be an important factor in viral induction.