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M9480119.TXT
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1994-08-09
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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).