CALCIUM-MEDIATED INHIBITION OF PHORBOL ESTER AND TAX TRANSACTIVATION OF THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1

Human Jurkat T cells containing a stably integrated human T cell leuka emia virus type 1 (HTLV-1) long terminal repeat (LTR) reporter gene co nstruct were used to study the role of calcium-dependent cellular acti vation pathways in LTR trans-activation. Treatment of these cells with the calcium ionophore ionomycin resulted in a reduced basal response of the LTR and reduced responses to 12-O-tetradecanoylphorbol-13-aceta te- and Tax-mediated trans-activation. This effect was also observed f or virus production in the HTLV-1-producing T cell line MT-2. Experime nts designed to determine the events underlying this inhibition, using inhibitors of calcium-related events, revealed that the ionomycin-ind uced repression of the LTR was alleviated in all cases by cyclosporin A. This compound was also effective in preventing the ionomycin-induce d reduction in virus production in MT-2 cells. These results suggest a role for calcium-related events in the down-regulation of HTLV-1 expr ession.