Cell Surface Expression of the Bovine Leukemia Virus-Binding Receptor on B and T Lymphocytes Is Induced by Receptor Engagement

Abstract

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.

Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

“…Studies by other groups clearly established that neutrophils are avid consumers of glucose (40) and that the upregulation of surface Glut1 expression is associated with neutrophil activation upon exposure to inflammatory conditions (41). A similar increase in glucose-dependent metabolism is seen in other activated leukocyte subsets, notably T and B cells (29,(42)(43)(44)(45). In contrast with Glut1, expression of the amino acid transporter ASCT2 is not uniformly increased on CF airway neutrophils (decreased on A1 and increased on A2 neutrophils compared with blood neutrophils, respectively).…”

Estimation of bovine leukemia virus (BLV) proviral load harbored by lymphocyte subpopulations in BLV-infected cattle at the subclinical stage of enzootic bovine leucosis using BLV-CoCoMo-qPCR

“…A previous report used the BLV envelope (ENV) receptor binding domain showed that BLV receptor molecules are expressed by pro/pre B cells (but not by mature/arrested B cells), by activated B and T cells (but not by arrested B and T cells), by human thymus cells induced by IL-7, and by proliferating lymphocytes [25]. CD4, CD8, and CD5 - IgM + B cells proliferate in an antigen-specific manner; however, CD5 + IgM + B cells can proliferate in the absence of antigen.…”

Bovine leukemia virus: A major silent threat to proper immune responses in cattle

“…Although BLV primarily infects B cells, it can infect other cell types (Lavanya et al, 2008), although this is rare. Even without direct infection of other immune cells, BLV infection not only impacts B cell function but also the function of other immune cells, particularly T cells.…”