title: Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites.
abstract: Human T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcription in vivo. Here, our in silico analysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region. We demonstrated that the Sp1 and Sp3 transcription factors bound in vitro to these two sites and compared the binding affinity for Sp1 of all six different HTLV-1 Sp1 sites. By chromatin immunoprecipitation experiments, we showed Sp1 recruitment in vivo to the newly identified Sp1 sites. We demonstrated in the nucleosomal context of an episomal reporter vector that the Sp1 sites interfered with both the sense and antisense LTR promoter activities. Interestingly, the Sp1 sites exhibited together a repressor effect on the LTR sense transcriptional activity but had no effect on the LTR antisense activity. Thus, our results demonstrate the presence of two new functional Sp1 binding sites in the HTLV-1 LTR, which act as negative cis-regulatory elements of sense viral transcription.
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fauquenoy
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Robette
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Kula
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vanhulle
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bouchat
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Delacourt
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodari
authors.affiliation: Biomaterials and Bioengineering, Inserm UMR 1121, Faculty of Dentistry, University of Strasbourg, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Marban
authors.affiliation: Institut Universitaire de Technologie Louis Pasteur, University of Strasbourg, Schiltigheim, France.|Laboratory of Dynamic of Host-Pathogen Interactions (DHPI), EA7292, University of Strasbourg, Strasbourg, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Arsène
authors.initials: A
authors.lastname: Burny
authors.affiliation: Institut Universitaire de Technologie Louis Pasteur, University of Strasbourg, Schiltigheim, France.|Laboratory of Dynamic of Host-Pathogen Interactions (DHPI), EA7292, University of Strasbourg, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rohr
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Van Driessche
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
mesh_terms: D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D063185:Epigenetic Repression; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000254:growth & development*; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000378:metabolism; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic
chemical_list: C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D051705:Sp3 Transcription Factor