Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcium / metabolism*
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Cell Line, Transformed
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Cyclosporine / pharmacology
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Gene Expression Regulation, Viral* / drug effects
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Gene Expression Regulation, Viral* / physiology
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Gene Products, tax / genetics
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Gene Products, tax / metabolism
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Genes, pX / physiology
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HTLV-I Antigens / biosynthesis
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Human T-lymphotropic virus 1 / genetics
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Human T-lymphotropic virus 1 / physiology*
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Humans
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Ionomycin / pharmacology
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Repetitive Sequences, Nucleic Acid / genetics
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Retroviridae Proteins, Oncogenic / biosynthesis
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T-Lymphocytes / metabolism*
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T-Lymphocytes / microbiology
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Tetradecanoylphorbol Acetate / pharmacology
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Transcriptional Activation* / drug effects
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beta-Galactosidase / biosynthesis
Substances
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Gene Products, tax
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HTLV-I Antigens
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Retroviridae Proteins, Oncogenic
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p24 protein, Human T-lymphotropic virus 1
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Egtazic Acid
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Ionomycin
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Cyclosporine
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beta-Galactosidase
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Tetradecanoylphorbol Acetate
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Calcium