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.
The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV
Manel, N.; Kim, F. J.; Kinet, S.; Taylor, N.; Sitbon, M.; Battini, J. L.
2003-11-14 / vol 115 / pages 449-59
Humans; Animals; Mice; Cell Line; RNA, Messenger/genetics/metabolism; RNA, Small Interfering/genetics/metabolism; Biological Transport/drug effects; Hela Cells; Cytochalasin B/pharmacology; Deltaretrovirus Antigens/metabolism; Glucose Transporter Type 1; Glucose/antagonists & inhibitors/metabolism; Human T-lymphotropic virus 1/*metabolism/physiology; Human T-lymphotropic virus 2/*metabolism/physiology; Lactic Acid/metabolism; Monosaccharide Transport Proteins/genetics/*metabolism; Protein Binding/drug effects; Receptors, Virus/genetics/*metabolism; Viral Envelope Proteins/metabolism