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.
Cell surface expression of the bovine leukemia virus-binding receptor on B and T lymphocytes is induced by receptor engagement
Lavanya§, M.; Kinet§, S.; Montel-Hagen, A.; Mongellaz, C.; Battini, J. L.; Sitbon*, M.; Taylor*, N.
2008-07-15 / vol 181 / pages 891-8
IGMM team(s) involved in this publication
Retroviruses, Envelopes and Metabolic Markers
Hematopoiesis and Immunotherapy
Cell Line, Tumor; Humans; Animals; Cells, Cultured; Mice; Protein Structure, Tertiary; Recombinant Fusion Proteins/metabolism; *Lymphocyte Activation; Antigens, CD/immunology/metabolism; B-Lymphocytes/*immunology/metabolism; Cattle; Deltaretrovirus/immunology/metabolism; Interleukin-7/immunology/metabolism; Leukemia Virus, Bovine/chemistry/immunology/*metabolism; Rabbits; Receptors, Virus/*metabolism; T-Lymphocytes/*immunology/metabolism; Thymus Gland; Up-Regulation; Viral Envelope Proteins/chemistry/*metabolism