Document Detail


GLUT-1-independent infection of the glioblastoma/astroglioma U87 cells by the human T cell leukemia virus type 1.
MedLine Citation:
PMID:  16781755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Qingwen Jin; Lokesh Agrawal; Zainab Vanhorn-Ali; Ghalib Alkhatib
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-06-16
Journal Detail:
Title:  Virology     Volume:  353     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-01     Completed Date:  2006-10-10     Revised Date:  2013-07-15    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  99-110     Citation Subset:  IM    
Affiliation:
Department of Neurology, Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.
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MeSH Terms
Descriptor/Qualifier:
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:
1R21CA98095-01/CA/NCI NIH HHS; R21 CA098095/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Glucose Transporter Type 1

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