Document Detail


Nef-mediated disruption of HLA-A2 transport to the cell surface in T cells.
MedLine Citation:
PMID:  12584329     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human immunodeficiency virus type 1 (HIV-1) Nef is a key pathogenic factor necessary for the development of AIDS. One important function of Nef is to reduce cell surface levels of major histocompatibility complex class I (MHC-I) molecules, thereby protecting HIV-infected cells from recognition by cytotoxic T lymphocytes. The mechanism of MHC-I downmodulation by Nef has not been clearly elucidated, and its reported effect on MHC-I steady-state levels ranges widely, from 2-fold in HeLa cells to 200-fold in HIV-infected primary T cells. Here, we directly compared downmodulation of HLA-A2 in HIV-infected HeLa cells to that in T cells. We found that similar amounts of Nef protein resulted in a much more dramatic downmodulation of HLA-A2 in T cells than in HeLa cells. A comparison of Nef's effects on HLA-A2 endocytosis, recycling, and transport rates indicated that the most prominent effect of Nef on HLA-A2 in T cells was to inhibit transport to the cell surface. The phosphatidylinositol 3-kinase inhibitor, LY294002, previously reported to inhibit Nef-mediated MHC-I downmodulation in astrocytic cells, did not directly affect Nef's ability to block transport of MHC-I to the cell surface in T cells.
Authors:
Matthew R Kasper; Kathleen L Collins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  77     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-13     Completed Date:  2003-03-20     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3041-9     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Cell Line
Cell Membrane / immunology,  metabolism*
Down-Regulation
Endocytosis
Gene Products, nef / genetics,  physiology*
Genetic Vectors
HIV-1 / genetics,  metabolism,  pathogenicity*
HLA-A2 Antigen / metabolism*
HeLa Cells
Humans
Protein Transport
T-Lymphocytes / immunology,  metabolism*
Transduction, Genetic
nef Gene Products, Human Immunodeficiency Virus
Grant Support
ID/Acronym/Agency:
R01 AI46998/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Gene Products, nef; 0/HLA-A2 Antigen; 0/nef Gene Products, Human Immunodeficiency Virus
Comments/Corrections

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