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Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5535/IFR 24, Université Montpellier I and II, Montpellier, France
Bovine leukemia virus (BLV), one of the most common infectious viruses of cattle, is endemic in many herds. Approximately 30–40% of adult cows in the United States are infected by this oncogenic C-type retrovirus and 1–5% of animals will eventually develop a malignant lymphoma. BLV, like the human and simian T cell leukemia viruses, is a deltaretrovirus but, in contrast with the latter, the BLV receptor remains unidentified. In this study, we demonstrate that the amino-terminal 182 residues of the BLV envelope glycoprotein surface unit encompasses the receptor-binding domain. A bona fide interaction of this receptor-binding domain with the BLV receptor was demonstrated by specific interference with BLV, but not human T cell leukemia virus, envelope glycoprotein-mediated binding. We generated a rabbit Ig Fc-tagged BLV receptor-binding domain construct and ascertained that the ligand binds the BLV receptor on target cells from multiple species. Using this tool, we determined that the BLV-binding receptor is expressed on differentiating pro/pre-B cells in mouse bone marrow. However, the receptor was not detected on mature/quiescent B cells but was induced upon B cell activation. Activation of human B and T lymphocytes also induced surface BLV-binding receptor expression and required de novo protein synthesis. Receptor levels were down-regulated as activated lymphocytes returned to quiescence. In the human thymus, BLV-binding receptor expression was specifically detected on thymocytes responding to the IL-7 cytokine. Thus, expression of the BLV-binding receptor is a marker of enhanced metabolic activity in B cells, T cells, and thymocytes.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Association Française Contre les Myopathies (to J.L.B., M.S., and N.T.), Association pour la Recherche sur le Cancer, and the Agence Nationale de Recherches sur le SIDA (to M.S. and N.T.), the European Community (Contract LSHC-CT-2005-018914 "ATTACK," to N.T.), and the Fondation de France (to M.S.). M.L. was supported by a grant from the Association Française Contre les Myopathies. J.L.B., N.T., and M.S. are supported by Institut National de la Santé et de la Recherche Médicale and S.K. by Centre National de la Recherche Scientifique.
2 M.L. and S.K. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. N. Taylor, M. Sitbon, or J. L. Battini, Institut de Génétique Moléculaire de Montpellier, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France. E-mail addresses: taylor{at}igmm.cnrs.fr, sitbon{at}igmm.cnrs.fr, and battini{at}igmm.cnrs.fr
4 Abbreviations used in this paper: BLV, bovine leukemia virus; HTLV, human T cell leukemia virus; SU, surface unit; RBD, receptor-binding domain; PRR, proline-rich region; rFC, rabbit Ig Fc; eGFP, enhanced GFP; LN, lymph node; MFI, mean fluorescence intensity; BM, bone marrow; SP, single positive; CHX, cycloheximide; DN, double negative; DP, double positive; Env, envelope glycoprotein.
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