Tpa Induction of Epstein-barr-virus Early Antigens In Raji Cells Is Blocked By Selective Protein-kinase-c Inhibitors

We have shown that modulation of intracellular calcium in EBV latently infected cells could induce the expression of viral an :igens, and suggested that a protein kinase-C (PKC) may play a major role in the EBV genome activation. We now report further investigations on the role of PKC using 2 selective enzymatic inhibitors [l-(5-lsoquinolinylsulfonyl)-2-meth-ylpiperazine] (H-7) and Staurosporine. We show that these inhibitors can abrogate the inductive effect of TPA or the combination of TPA plus n-butyrate. The inhibitors have no effisct on induction by calcium ionophores or by viral super-infection. In this context the effect of verapamil (a specific calcium channel blocker) and of several calmodulin antagonists was investigated. No inhibitory effect of these agents could be demonstrated on any of the induction systems examined. These observations strengthen the idea that in some instances cellular PKC plays a role in the expression of viral antigens; however, alternative regulatory mechanisms cannot be excluded.