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Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat

Oncogene volume 22, pages 2882–2896 (2003)Cite this article

Abstract

Bovine leukemia virus (BLV) is a B-lymphotropic oncogenic retrovirus whose transcriptional promoter is located in the viral 5′ long terminal repeat (LTR). To date, no B-lymphocyte-specific cis-regulatory element has been identified in this region. Since ETS proteins are known to regulate transcription of numerous retroviruses, we searched for the presence in the BLV promoter region of binding sites for PU.1/Spi-1, a B-cell- and macrophage-specific ETS family member. In this report, nucleotide sequence analysis of the viral LTR identified a PUbox located at −95/−84 bp. We demonstrated by gel shift and supershift assays that PU.1 and the related Ets transcription factor Spi-B interacted specifically with this PUbox. A 2-bp mutation (GGAA→CCAA) within this motif abrogated PU.1/Spi-B binding. This mutation caused a marked decrease in LTR-driven basal gene expression in transient transfection assays of B-lymphoid cell lines, but did not impair the responsiveness of the BLV promoter to the virus-encoded transactivator TaxBLV. Moreover, ectopically expressed PU.1 and Spi-B proteins transactivated the BLV promoter in a PUbox-dependent manner. Taken together, our results provide the first demonstration of regulation of the BLV promoter by two B-cell-specific Ets transcription factors, PU.1 and Spi-B. The PU.1/Spi-B binding site identified here could play an important role in BLV replication and B-lymphoid tropism.

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Acknowledgements

We thank Drs Luc Willems and Richard Kettmann (Faculty of Agronomy, Gembloux, Belgium) for the gift of the eukaryotic expression vector pSG-TAXBLV, Dr Shigetaka Kitajima (Medical Research Institute, Tokyo, Japan) for the gift of the anti-GABP antibody, Dr Vincent Bours (Center for Molecular and Cellular Therapy, Université de Liège, Belgium) for the gift of the GST-p50 and GST-p65 vectors, Dr Meinrad Busslinger (Research Institute of Molecular Pathology, Vienna, Austria) for the gift of the anti-Pax5 antibody, and Drs Françoise Moreau-Gachelin (Institut Curie, Paris, France) and Simon Celeste (Howard Hughes Medical Institute, Philadelphia, Pennsylvania) for the gift of Spi-B reagents. This work was supported by grants to CVL from the ‘Fonds National de la Recherche Scientifique’ (FNRS, Belgium), the FNRS-Télévie Program, the Free University of Brussels (ARC program 98/03-224), the Internationale Brachet Stiftung (IBS), the CGRI-INSERM cooperation, the Region Wallonne-Commission Européenne FEDER and the Theyskens-Mineur Foundation. CVL and AD are ‘Maître de Recherches’ and ‘Aspirant’ of the FNRS, respectively. CC and SN are fellows of the FNRS-Télévie Program.

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  1. Ann Dekoninck and Claire Calomme: These two authors contributed equally to this work.

Authors and Affiliations

  1. Laboratoire de Virologie Moléculaire, Service de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Rue des Profs Jeener et Brachet 12, Gosselies, 6041, Belgium

    Ann Dekoninck, Claire Calomme, Séverine Nizet, Arsène Burny & Carine Van Lint

  2. Laboratoire de Virologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, 808 Route de Lennik, Bruxelles, 1070, Belgium

    Yvan de Launoit

  3. Institut Pasteur de Lille, Institut de Biologie de Lille, Université de Lille 1, UMR 8117 CNRS, 1 Rue Calmette BP 447, Lille, 59021, Cedex, France

    Yvan de Launoit

  4. UMR 146 CNRS-Institut Curie, Centre Universitaire, bât. 110, Orsay, 91405, France

    Jacques Ghysdael

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  1. Ann Dekoninck
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Dekoninck, A., Calomme, C., Nizet, S. et al. Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat. Oncogene 22, 2882–2896 (2003). https://doi.org/10.1038/sj.onc.1206392

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