Document 0119 DOCN M9480119 TI Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1. DT 9410 AU Copeland KF; Haaksma AG; Goudsmit J; Heeney JL; Department of Chronic and Infectious DiseaseS, TNO-Rijswijk, The; Netherlands. SO J Gen Virol. 1994 Jul;75 ( Pt 7):1623-31. Unique Identifier : AIDSLINE MED/94292913 AB Human Jurkat T cells containing a stably integrated human T cell leukaemia virus type 1 (HTLV-1) long terminal repeat (LTR) reporter gene construct were used to study the role of calcium-dependent cellular activation 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-acetate-and Tax-mediated trans-activation. This effect was also observed for virus production in the HTLV-1-producing T cell line MT-2. Experiments designed to determine the events underlying this inhibition, using inhibitors of calcium-related events, revealed that the ionomycin-induced repression of the LTR was alleviated in all cases by cyclosporin A. This compound was also effective in preventing the ionomycin-induced reduction in virus production in MT-2 cells. These results suggest a role for calcium-related events in the down-regulation of HTLV-1 expression. DE beta-Galactosidase/BIOSYNTHESIS Calcium/*METABOLISM Cell Line, Transformed Cyclosporine/PHARMACOLOGY Egtazic Acid/ANALOGS & DERIVATIVES/PHARMACOLOGY *Gene Expression Regulation, Viral/DRUG EFFECTS/PHYSIOLOGY Gene Products, tax/GENETICS/METABOLISM Genes, pX/PHYSIOLOGY Human HTLV-I/GENETICS/*PHYSIOLOGY HTLV-I Antigens/BIOSYNTHESIS Ionomycin/PHARMACOLOGY Repetitive Sequences, Nucleic Acid/GENETICS Retroviridae Proteins, Oncogenic/BIOSYNTHESIS Support, Non-U.S. Gov't T-Lymphocytes/*METABOLISM/MICROBIOLOGY Tetradecanoylphorbol Acetate/PHARMACOLOGY *Trans-Activation (Genetics)/DRUG EFFECTS JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).