Human T-lymphotropic virus type 1 p30II functions as a transcription factor and differentially modulates CREB-responsive promoters

W. Zhang, J. W. Nisbet, J. T. Bartoe, Wei D Ding, M. D. Lairmore

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)11270-11277
Number of pages8
JournalJournal of Virology
Volume74
Issue number23
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Human T-lymphotropic virus 1
Transcription Factors
Reporter Genes
transcription factors
promoter regions
reporter genes
viruses
DNA-binding domains
Open Reading Frames
DNA
open reading frames
Virus Replication
Luciferases
taxes
Transfection
transfection
luciferase
Proteins
proteins
POU Domain Factors

ASJC Scopus subject areas

  • Immunology

Cite this

Human T-lymphotropic virus type 1 p30II functions as a transcription factor and differentially modulates CREB-responsive promoters. / Zhang, W.; Nisbet, J. W.; Bartoe, J. T.; Ding, Wei D; Lairmore, M. D.

In: Journal of Virology, Vol. 74, No. 23, 2000, p. 11270-11277.

Research output: Contribution to journalArticle

Zhang, W. ; Nisbet, J. W. ; Bartoe, J. T. ; Ding, Wei D ; Lairmore, M. D. / Human T-lymphotropic virus type 1 p30II functions as a transcription factor and differentially modulates CREB-responsive promoters. In: Journal of Virology. 2000 ; Vol. 74, No. 23. pp. 11270-11277.
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