The Receptor Complex Associated with Human T-Cell Lymphotropic Virus Type 3 (HTLV-3) Env-Mediated Binding and Entry Is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2

Abstract

Little is known about the transmission or tropism of the newly discovered human retrovirus, human T-cell lymphotropic virus type 3 (HTLV-3). Here, we examine the entry requirements of HTLV-3 using independently expressed Env proteins. We observed that HTLV-3 surface glycoprotein (SU) binds efficiently to both activated CD4 ؉ and CD8 ؉ T cells. This contrasts with both HTLV-1 SU, which primarily binds to activated CD4 ؉ T cells, and HTLV-2 SU, which primarily binds to activated CD8 ؉ T cells. Binding studies with heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), two molecules important for HTLV-1 entry, revealed that these molecules also enhance HTLV-3 SU binding. However, unlike HTLV-1 SU, HTLV-3 SU can bind efficiently in the absence of both HSPGs and NRP-1. Studies of entry performed with HTLV-3 Env-pseudotyped viruses together with SU binding studies revealed that, for HTLV-1, glucose transporter 1 (GLUT-1) functions at a postbinding step during HTLV-3 Env-mediated entry. Further studies revealed that HTLV-3 SU binds efficiently to naïve CD4 ؉ T cells, which do not bind either HTLV-1 or HTLV-2 SU and do not express detectable levels of HSPGs, NRP-1, and GLUT-1. These results indicate that the complex of receptor molecules used by HTLV-3 to bind to primary T lymphocytes differs from that of both HTLV-1 and HTLV-2.

Genetic characterization of the complete genome of a highly divergent simian T-lymphotropic virus (STLV) type 3 from a wild Cercopithecus mona monkey

“…Unfortunately, serum or plasma was not available from animals Cmo8699AB and Cni7867AB to confirm this hypothesis. The STLV-3d(Cmo8699AB) SU also contains highly conserved residues believed important for viral entry (data not shown) similar to those described recently for HTLV-3b(Pyl43) [ 47 ].…”

HTLV-3/4 and simian foamy retroviruses in humans: Discovery, epidemiology, cross-species transmission and molecular virology

“…HTLV-3/-4 tropism in vivo is currently unknown, yet it is clear that the virus infects at least cells that belong to PBMCs. As HTLV-1/-2, which, in addition to dendritic cells, infect activated CD4þ and CD8þ T cells, respectively in vivo, we have shown that HTLV-3 surface envelope glycoprotein (gp46 or SU) binds to both activated CD4þ and CD8þ T, but also to naïve CD4þ T cells (Jones et al, 2009). The latter do not bind HTLV-1 or HTLV-2 SU and do not express detectable levels of heparan sulfate proteoglycans (HSPGs), neuropilin-1 (NRP-1) and Glucose transporter 1 (GLUT-1).…”

Current concepts regarding the HTLV-1 receptor complex

“…An earlier study reported that overexpression of GLUT1 in a cell line (COS-7) increased cell-cell transmission, but did not increase the level of binding of the SU-Fc protein [ 57 ]. Similarly, more recent studies using clones of the U87 cell line that express different levels of GLUT1 have observed that the level of cell surface GLUT1 correlates with the titer of HTLV-1 Env pseudotyped viruses, but not with SU-Fc binding [ 58 ]. All these findings suggested that molecules other than GLUT1 are also involved in HTLV-1 entry, especially at the binding step.…”