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J Gen Virol 75 (1994), 1623-1631; DOI 10.1099/0022-1317-75-7-1623
© 1994 Society for General Microbiology
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Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1

Karen F. T. Copeland1, Anthonius G. M. Haaksma1, Jaap Goudsmit2 and Jonathan L. Heeney1

1 Laboratory of Viral Pathogenesis, Department of Chronic and Infectious Diseases, TNO-Rijswijk
and2 Human Retrovirus Laboratory, Department of Medical Virology, Academic Medical Centre, Amsterdam, The Netherlands

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.

Received 15 November 1993; accepted 10 January 1994.




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Copyright © 1994 by the Society for General Microbiology.