Modulation by the Polyoxotungstate HPA-23 of Epstein--Barr Virus Early Antigen Expression in Raji Cells Treated with Iododeoxyuridine

Abstract

Summary The polyoxotungstate HPA-23 was found to exert a differential effect on the induction of Epstein—Barr virus early antigen in Raji cells induced with 5-iodo-2′-deoxyuridine (IUdR). Thus, treatment of Raji cells concomitantly with IUdR and HPA-23 inhibited early antigen expression, and the extent of inhibition was proportional to the duration of treatment with HPA-23. In contrast, pretreatment of Raji cells with HPA-23 prior to induction with IUdR stimulated early antigen expression in exponentially multiplying but not in stationary-phase cells. HPA-23 alone had no effect one arly antigen expression in Raji cells. Activation of the latent Epstein—Barr virus genome by IUdR is dependent upon incorporation of the thymidine analogue into cellular DNA during the S-phase of the cell cycle. Synthesis of Epstein—Barr virus DNA also takes place during S-phase, suggesting a possible participation in this process of cellular DNA polymerase α which is thought to be responsible for cellular DNA replication and the activity of which increases several-fold during S-phase. Treatment of Raji cells with HPA-23 caused a marked decrease in DNA polymerase α activity, which could result in an inhibition of IUdR incorporation leading to the observed reduction of early antigen expression in cells treated concomitantly with IUdR and HPA-23.