Previous Article | Next Article ![]()
Journal of Virology, December 2000, p. 11270-11277, Vol. 74, No. 23
Center for Retrovirus Research and Department
of Veterinary Biosciences,1
Comprehensive Cancer Center, The Arthur James Cancer
Hospital and Research Institute,2 and
Department of Molecular Virology, Immunology, and Medical
Genetics,3 The Ohio State University, Columbus,
Ohio 43210
Received 3 July 2000/Accepted 1 September 2000
Human T-lymphotropic virus type 1 (HTLV-1), a complex retrovirus,
causes adult T-cell lymphoma/leukemia and is linked to a variety of
immune-mediated disorders. The roles of proteins encoded in the pX open
reading frame (ORF) II gene region in HTLV-1 replication or in
mediating virus-associated diseases remain to be defined. A
nucleus-localizing 30-kDa protein, p30II, encoded within pX
ORF II has limited homology with the POU family of transcription
factors. Recently, we reported that selected mutations in pX ORF II
diminish the ability of HTLV-1 to maintain high viral loads in infected
rabbits. Herein we have tested the transcriptional ability of
p30II in mammalian cells by using yeast Gal4 fusion protein
vectors and transfection of luciferase reporter genes driven by
CREB-responsive promoters. p30II as a Gal4 DNA-binding
domain (DBD) fusion protein transactivates Gal4-driven luciferase
reporter gene activity up to 25-fold in 293 and HeLa-tat cells. We
confirmed nuclear localization of p30II and demonstrate
dose-dependent binding of p30II-Gal4(DBD) to Gal4
DNA-binding sites. The transcriptional activity of
p30II-Gal4(DBD) was independent of TATA box flanking
sequences, as shown by using two different Gal4 reporter systems.
Studies of selected p30II mutants indicated that domains
that mediate transcription are restricted to a central core region of
the protein between amino acids 62 and 220. Transfection of a
p30II-expressing plasmid repressed cellular CRE-driven
reporter gene activity, with or without Tax expression. In contrast,
p30II at lower concentrations enhanced HTLV-1 long terminal
repeat-driven reporter gene activity independent of Tax expression.
These data are the first to demonstrate a transcriptional function for
p30II and suggest a mechanism by which this nuclear protein
may influence HTLV-1 replication or cellular gene expression in vivo.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Human T-Lymphotropic Virus Type 1 p30II
Functions as a Transcription Factor and Differentially Modulates
CREB-Responsive Promoters
*
Corresponding author. Mailing address: Department of
Veterinary Biosciences, The Ohio State University, 1925 Coffey Rd.,
Columbus, OH 43210-1093. Phone: (614) 292-4819. Fax: (614) 292-6473. E-mail: lairmore.1{at}osu.edu.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|