Human T cell leukemia virus envelope binding and virus entry are mediated by distinct domains of the glucose transporter GLUT1.
The glucose transporter GLUT1, a member of the multimembrane-spanning facilitative nutrient transporter family, serves as a receptor for human T cell leukemia virus (HTLV) infection. Here, we show that the 7 amino acids of the extracellular loop 6 of GLUT1 (ECL6) placed in the context of the related GLUT3 transporter were sufficient for HTLV envelope binding. Glutamate residue 426 in ECL6 was identified as critical for binding. However, binding to ECL6 was not sufficient for HTLV envelope-driven infection. Infection required two additional determinants located in ECL1 and ECL5, which otherwise did not influence HTLV envelope binding. Moreover the single N-glycosylation chain located in ECL1 was not required for HTLV infection. Therefore, binding involves a discrete determinant in the carboxyl terminal ECL6, whereas post-binding events engage extracellular sequences in the amino and carboxyl terminus of GLUT1.
Manel
Nicolas
N
Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, IFR 122, 1919 route de Mende, F-34293 Montpellier Cedex 5, France.
Battini
Jean-Luc
JL
Sitbon
Marc
M
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002460:Cell Line; D017977:Deltaretrovirus / Q000378:metabolism*; D015686:Gene Products, env / Q000737:chemistry / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D018698:Glutamic Acid / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D007763:Lac Operon; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D015682:Retroviridae Proteins, Oncogenic; C495677:SLC2A1 protein, human; C055266:gp46 protein, Human T-cell leukemia virus type I; D018698:Glutamic Acid; D005947:Glucose