HTLV envelopes and their receptor GLUT1, the ubiquitous glucose transporter: a new vision on HTLV infection?
We identified the ubiquitous glucose transporter GLUT1 as a receptor for Deltaretroviruses HTLV-1 and HTLV-2 envelopes (Env), mediating viral binding and entry. Here, we review the context and key observations that led us to this finding: functional modules of HTLV SU are similar to those of Gammaretrovirus Env which use multimembrane-spanning nutrient transporters as receptors; the HTLV Env receptor is an early marker of T lymphocyte activation; and HTLV Env inhibits glucose transport. We review several molecular, viral, cellular and physiological aspects of HTLV infection in relation to the in vivo and in vitro properties of GLUT1. Also, we examine the implications of HTLV-1 Env-GLUT1 interactions and altered glucose transport on the two major HTLV-1-induced diseases, adult T cell leukemia (ATL) and neurodegenerative tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM). Complementary to the classical models of disease progression, we propose new schemes that emphasize the potential metabolic alterations caused in different cellular compartments. Finally, we review the potential use of HTLV Env-derived constructs as tools for labeling GLUT1 in vivo and inhibiting GLUT1 transport in tumor cells.
Manel
Nicolas
N
Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535/IFR 122, F-34293 Montpellier Cedex 5, France.
Taylor
Naomi
N
Kinet
Sandrina
S
Kim
Felix J
FJ
Swainson
Louise
L
Lavanya
Madakasira
M
Battini
Jean-Luc
JL
Sitbon
Marc
M
D000818:Animals; D001692:Biological Transport; D006800:Deltaretrovirus Infections / Q000378:metabolism*; D015686:Gene Products, env / Q000378:metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015458:Leukemia, T-Cell / Q000821:virology; D008213:Lymphocyte Activation; D015493:Paraparesis, Tropical Spastic / Q000821:virology; D011485:Protein Binding
D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D005947:Glucose