Journal of Virology, June 1999, p. 4856-4865, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Departments of Medicine, Pathology, and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110
Received 25 November 1998/Accepted 8 March 1999
The human T-cell leukemia virus type 1 (HTLV-1) transcriptional
trans-activator Tax has been demonstrated to have
transforming activity in multiple cell culture and transgenic-mouse
models. In addition to activating transcription from the viral long
terminal repeat (LTR) through the cyclic AMP response element binding
protein/activating transcription factor (CREB/ATF) family of
transcription factors, Tax activates the expression of multiple
cellular promoters through the NF-
B pathway of transcriptional
activation. The Tax mutants M22 and M47 have previously been
demonstrated to selectively abrogate the ability of Tax to activate
transcription through the NF-
B or CREB/ATF pathway, respectively.
These mutations were introduced in the tax gene of the ACH
functional molecular clone of HTLV-1, and virus produced from the
mutant ACH clones was examined for the ability to replicate and
immortalize primary human lymphocytes. While virus derived from the
clone containing the M47 mutation retained the ability to immortalize T
lymphocytes, the M22 mutant lost the ability to immortalize infected
cells. These results indicate that activation of the CREB/ATF pathway
by Tax is dispensable for the immortalization of T cells by HTLV-1,
whereas activation of the NF-
B pathway may be critical.
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