The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV.
The human T cell leukemia virus (HTLV) is associated with leukemia and neurological syndromes. The physiopathological effects of HTLV envelopes are unclear and the identity of the receptor, present on all vertebrate cell lines, has been elusive. We show that the receptor binding domains of both HTLV-1 and -2 envelope glycoproteins inhibit glucose transport by interacting with GLUT-1, the ubiquitous vertebrate glucose transporter. Receptor binding and HTLV envelope-driven infection are selectively inhibited when glucose transport or GLUT-1 expression are blocked by cytochalasin B or siRNAs, respectively. Furthermore, ectopic expression of GLUT-1, but not the related transporter GLUT-3, restores HTLV infection abrogated by either GLUT-1 siRNAs or interfering HTLV envelope glycoproteins. Therefore, GLUT-1 is a receptor for HTLV. Perturbations in glucose metabolism resulting from interactions of HTLV envelope glycoproteins with GLUT-1 are likely to contribute to HTLV-associated disorders.
Manel
Nicolas
N
Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535/IFR 122, F-34293 Montpellier Cedex 5, France.
Kim
Felix J
FJ
Kinet
Sandrina
S
Taylor
Naomi
N
Sitbon
Marc
M
Battini
Jean-Luc
JL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D015485:Deltaretrovirus Antigens / Q000378:metabolism; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism* / Q000502:physiology; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism
D015485:Deltaretrovirus Antigens; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C495677:SLC2A1 protein, human; C495678:Slc2a1 protein, mouse; D014759:Viral Envelope Proteins; D019344:Lactic Acid; D003571:Cytochalasin B; D005947:Glucose