Infection of CD4{sup +} T lymphocytes by the human T cell leukemia virus type 1 is mediated by the glucose transporter GLUT-1: Evidence using antibodies specific to the receptor's large extracellular domain

Journal Article · Thu May 25 04:00:00 EDT 2006 · Virology

DOI:https://doi.org/10.1016/j.virol.2006.01.045· OSTI ID:20850515

Jin, Qingwen ^[1]; Agrawal, Lokesh ^[1]; VanHorn-Ali, Zainab ^[1]; Alkhatib, Ghalib ^[1]

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1. Department of Microbiology and Immunology and the Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN 46202-5114 (United States)

To analyze HTLV-1 cytotropism, we developed a highly sensitive vaccinia virus-based assay measuring activation of a reporter gene upon fusion of two distinct cell populations. We used this system in a functional cDNA screening to isolate and confirm that the glucose transporter protein 1 (GLUT-1) is a receptor for HTLV-1. GLUT-1 is a ubiquitously expressed plasma membrane glycoprotein with 12 transmembrane domains and 6 extracellular loops (ECL). We demonstrate for the first time that peptide antibodies (GLUT-IgY) raised in chicken to the large extracellular loop (ECL1) detect GLUT-1 at the cell surface and inhibit envelope (Env)-mediated fusion and infection. Efficient GLUT-IgY staining was detected with peripheral blood CD4{sup +} lymphocytes purified by positive selection. Further, GLUT-IgY caused efficient inhibition of Env-mediated fusion and infection of CD4{sup +} T and significantly lower inhibition of CD8{sup +} T lymphocytes. The specificity of GLUT-IgY antibodies to GLUT-1 was demonstrated by ECL1 peptide competition studies. Grafting ECL1 of GLUT-1 onto the receptor-negative GLUT-3 conferred significant receptor activity. In contrast, grafting ECL1 of GLUT-3 onto GLUT-1 resulted in a significant loss of the receptor activity. The ECL1-mediated receptor activity was efficiently blocked with four different human monoclonal antibody (HMab) to HTLV-1 Env. The ECL1-derived peptide blocked HTLV-1 Env-mediated fusion with several nonhuman mammalian cell lines. The results demonstrate the utilization of cell surface GLUT-1 in HTLV-1 infection of CD4{sup +} T lymphocytes and implicate a critical role for the ECL1 region in viral tropism.

• OSTI ID: 20850515
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 349; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHICKENS
CLEAVAGE
GENES
GLUCOSE
GLYCOPROTEINS
INHIBITION
LEUKEMIA
LEUKEMIA VIRUSES
LYMPHOCYTES
MEMBRANES
MONOCLONAL ANTIBODIES
MUTANTS
PEPTIDES
RECEPTORS
SPECIFICITY
VACCINIA VIRUS