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Human T-lymphotropic virus type I tax regulates the expression of the human
lymphotoxin gene
E Tschachler, E Bohnlein, S Felzmann and MS Reitz
Department of Dermatology, University of Vienna Medical School, Austria.
Human T-lymphotropic virus type-I (HTLV-I)-infected T-cell lines
constitutively produce high levels of lymphotoxin (LT). To analyze the
mechanisms that lead to the expression of LT in HTLV-I-infected cell lines,
we studied regulatory regions of the human LT promoter involved in the
activation of the human LT gene. As determined by deletional analysis,
sequences between +137 and -116 (relative to the transcription initiation
site) are sufficient to direct expression of a reporter gene in the
HTLV-I-infected cell line MT-2. Site-directed mutation of a of the single
kappa B-like motif present in the LT promoter region (positions -99 to -89)
completely abrogated LT promoter activity in MT-2 cells, suggesting that
this site plays a critical role in the activation of the human LT gene.
Transfection of LT constructs into HTLV-I-uninfected and -unstimulated
Jurkat and U937 cell lines showed little to no activity of the LT promoter.
Cotransfection of the same constructs with a tax expression plasmid into
Jurkat cells led to detectable promoter activity, which could be
significantly increased by stimulation of the cells with phorbol myristate
acetate (PMA). Similarly, cotransfection of the LT promoter constructs and
the tax expression plasmid into U937 cells led to significant promoter
activity upon stimulation with PMA. These data suggest that HTLV-I tax is
involved in the upregulation of LT gene expression in HTLV-I-infected
cells.
Volume 81,
Issue 1,
pp. 95-100,
01/01/1993
Copyright © 1993 by The American Society of Hematology

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