HTLV-1 tropism and envelope receptor

Abstract

The identification of CD4 as the primary receptor for HIV followed shortly after the discovery of the virus, but the HTLV receptor remained long elusive, until its recent identification as the GLUT1 glucose transporter. In the present review, we describe the status of the literature that surrounded this discovery as well as the in vitro and in vivo observations that led to the identification of GLUT1. Also, we will explore a few tracks to conciliate the in vitro and in vivo data on HTLV-1 tropism within the context of the HTLV literature that has accumulated over the past 25 years. A close examination of these data leads us to conclude that the preferential detection of HTLV-1 in CD4 þ T lymphocyte subsets in vivo, even in the absence of leukemia, is not likely to be directly related to envelope receptor interactions, but rather to an array of postentry selection bottlenecks in vivo. Furthermore, we propose that infection of other hematopoietic and nonhematopoietic cells is likely to take place during the lifetime of an individual, with a burst early during the infection. Oncogene (2005) 24, 6016-6025.

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

“…Although there was some variability in the level of B RBD rFc binding, the flow cytometry results demonstrate an apparent ubiquitous expression (Fig. 3A), similar to that described for the related HTLV receptor (24,37,38).…”

“…Deltaretroviruses, including BLV, share the same modular envelope organization as gammaretroviruses, even in the variable regions of the protein surface unit (SU) (17)(18)(19), oligomerizing as a trimer (20 -22). Although the SU has been hypothesized to harbor the putative receptor-binding domain (RBD) (18,23,24), it is significant that the cellular receptor for BLV has yet to be identified. One reported candidate (25) was later shown to correspond to the Ѩ subunit of the adaptor-protein complex AP3, involved in intracellular transport rather than cell surface binding (26).…”

“…Using a soluble-tagged construct encompassing this region (H RBD ), we were able to track HTLV receptor expression in lymphocyte subsets (28) and identified Glut1, the ubiquitous vertebrate glucose as a receptor for HTLV-1 and -2 Env (19, 29 -31). It is of particular interest that Glut1, a deltaretrovirus receptor, like all other identified gammaretrovirus receptors, is a multimembrane-spanning nutrient transporter (19,24,32).…”

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

“…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. We assessed cell surface expression of these transporters in five human breast cancer models with different molecular characteristics (Supplementary Table 1) and found that the transporter expression profile of each tumor was unique ( Figure 6).…”

“…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. We designed RBD probes, derived from gamma-and deltaretroviral Env, as specific ligands that bind to these cell surface transporters.…”