Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1.
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.
Department of Chronic and Infectious DiseaseS, TNO-Rijswijk, The Netherlands.
K F
KF
Copeland
A G
AG
Haaksma
J
J
Goudsmit
J L
JL
Heeney
D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D016355:Genes, pX / Q000502:physiology; D015486:HTLV-I Antigens / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D001616:beta-Galactosidase / Q000096:biosynthesis
D016356:Gene Products, tax; D015486:HTLV-I Antigens; D015682:Retroviridae Proteins, Oncogenic; C060954:p24 protein, Human T-lymphotropic virus 1; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D015759:Ionomycin; D016572:Cyclosporine; D001616:beta-Galactosidase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium