| GLUT-1-independent infection of the glioblastoma/astroglioma U87 cells by the human T cell leukemia virus type 1. | |
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MedLine Citation:
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PMID: 16781755 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The human glucose transporter protein 1 (GLUT-1) functions as a receptor for human T cell leukemia virus (HTLV). GLUT-1 is a twelve-transmembrane cell surface receptor with six extracellular (ECL) and seven intracellular domains. To analyze HTLV-1 cytotropism, we utilized polyclonal antibodies to a synthetic peptide corresponding to the large extracellular domain of GLUT-1. The antibodies caused significant blocking of envelope (Env)-mediated fusion and pseudotyped virus infection of HeLa cells but had no significant effect on infection of U87 cells. This differential effect correlated with the detection of high-level surface expression of GLUT-1 on HeLa cells and very weak staining of U87 cells. To investigate this in terms of viral cytotropism, we cloned GLUT-1 cDNA from U87 cells and isolated two different versions of cDNA clones: the wild-type sequence (encoding 492 residues) and a mutant cDNA with a 5-base pair deletion (GLUT-1Delta5) between nucleotides 1329 and 1333. The deletion, also detected in genomic DNA, resulted in a frame-shift and premature termination producing a truncated protein of 463 residues. Transfection of the wild-type GLUT-1 but not GLUT-1Delta5 cDNA into CHO cells resulted in efficient surface expression of the human GLUT-1. Co-expression of GLUT-1 with GLUT-1Delta5 produces a trans-inhibition by GLUT-1Delta5 of GLUT-1-mediated HTLV-1 envelope (Env)-mediated fusion. Co-immunoprecipitation experiments demonstrated physical interaction of the wild-type and mutant proteins. Northern blot and RT-PCR analyses demonstrated lower GLUT-1 RNA expression in U87 cells. We propose two mechanisms to account for the impaired cell surface expression of GLUT-1 on U87 cells: low GLUT-1 RNA expression and the formation of GLUT-1/GLUT-1Delta5 heterodimers that are retained intracellularly. Significant RNAi-mediated reduction of endogenous GLUT-1 expression impaired HTLV-1 Env-mediated fusion with HeLa cells but not with U87 cells. We propose a GLUT-1-independent mechanism of HTLV-1 infection of U87 cells. The results may have important implications for HTLV-1 neurotropism and pathogenesis. |
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Authors:
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Qingwen Jin; Lokesh Agrawal; Zainab Vanhorn-Ali; Ghalib Alkhatib |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-06-16 |
Journal Detail:
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Title: Virology Volume: 353 ISSN: 0042-6822 ISO Abbreviation: Virology Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-01 Completed Date: 2006-10-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0110674 Medline TA: Virology Country: United States |
Other Details:
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Languages: eng Pagination: 99-110 Citation Subset: IM |
Affiliation:
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Department of Neurology, Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytoma / pathology, virology* CHO Cells Cell Line, Tumor Cricetinae DNA, Complementary Frameshift Mutation Glioblastoma / pathology, virology* Glucose Transporter Type 1 / analysis, genetics, immunology, physiology* HTLV-I Infections / virology* Hela Cells Human T-lymphotropic virus 1 / physiology* Humans |
| Grant Support | |
ID/Acronym/Agency:
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1R21CA98095-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/Glucose Transporter Type 1 |
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