Isolated receptor binding domains of HTLV-1 and HTLV-2 envelopes bind Glut-1 on activated CD4+ and CD8+ T cells

Abstract

Background: We previously identified the glucose transporter Glut-1, a member of the multimembrane-spanning facilitative nutrient transporter family, as a receptor for both HTLV-1 and HTLV-2. However, a recent report concluded that Glut-1 cannot serve as a receptor for HTLV-1 on CD4 T cells: This was based mainly on their inability to detect Glut-1 on this lymphocyte subset using the commercial antibody mAb1418. It was therefore of significant interest to thoroughly assess Glut-1 expression on CD4 and CD8 T cells, and its association with HTLV-1 and -2 envelope binding.

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

“…The homology and similar organization of the HTLV and BLV envelopes and their similar cell-type and species distribution made it important to test whether Glut1, the recently identified HTLV receptor, is recognized by the BLV envelope. As expected, transfection of 293T cells with a Glut1 expression vector resulted in a significantly increased level of binding to its HTLV Env SU ligand (H RBD rFc) (28,31). Indeed, the MFI of H RBD rFc binding was ϳ10-fold higher in the Glut1-transfected population as compared with the untransfected cells (Fig.…”

“…Like B cells, the vast majority of circulating T lymphocytes are quiescent and are considered to have a very low metabolic activity, with very low glucose uptake (31). As such, it was not surprising to note that as in B cells, the BLV Env-binding receptor was not detected on quiescent human T lymphocytes.…”

Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters

“…Although other transporters, such as Glut isoforms, transporters of folate, glutamate, organic cations or platinum and many others, would also be relevant and valuable to monitor, their detection at the cell surface has been nearly impossible to perform on live cells due to the notorious lack of reliable antibodies directed against exofacial epitopes of multipass nutrient transporters. 5,6 Here, the use of four ligands that bind Glut1, ASCT2, PiT1 and PiT2 did not allow a predictive distinction of the tumor phenotype. However, we are exploring a larger panel of tumors with these ligands and a series of additional ligands derived from a variety of gammaretroviruses whose Env recognizes a receptor on human cells.…”

“…5,6 Here, cell surface expression of four metabolite transporters was monitored using retroviral RBDs that bind to the exofacial determinants of Glut1, ASCT2, PiT1 and PiT2. These transporters are cognate receptors for HTLV, 11,28 feline RD114 endogenous retrovirus, 29 KoRV 30 and amphotropic murine leukemia virus 7,8,30,31 Env, respectively.…”

“…4 However, the monitoring of metabolite and nutrient transporters at the cell surface has been hampered by the paucity, if not total lack, of exofacial antibodies to such transporters. 5,6 Cell entry of gamma-and deltaretroviruses occurs via recognition of membrane metabolite transporters by retroviral envelope glycoproteins (Env). 7,8 Viral entry occurs following the specific binding of the amino-terminal receptor binding domain (RBD) of an individual Env with its cognate receptor.…”