Document Detail


Inhibition of lipid antigen presentation in dendritic cells by HIV-1 Vpu interference with CD1d recycling from endosomal compartments.
MedLine Citation:
PMID:  20530791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dendritic cells (DCs) play an important role in viral infections both as initiators of immunity and as viral targets. Interaction between DCs and the innate-like CD1d-restricted natural killer T (NKT) cells results in the mutual activation of both cells and the subsequent initiation of cellular immune responses. Here, we show that HIV-1 inhibits the surface expression of CD1d in productively infected DCs and identify this as a novel activity of the HIV-1 vpu gene product. Interestingly, the viral protein U (Vpu) does not enhance constitutive CD1d endocytosis or induce rapid CD1d degradation. Instead, the Vpu protein interacts with CD1d and suppresses its recycling from endosomal compartments to the cell surface by retaining CD1d in early endosomes. This interference with the CD1d antigen presentation pathway strongly inhibits the ability of infected DCs to activate CD1d-restricted NKT cells. Given that the interaction with CD1d-expressing DCs is central to the ability of NKT cells to regulate immunity, these data suggest that interference with the CD1d antigen presentation pathway represents an HIV-1 strategy to evade innate cellular immune responses and imply a role for the innate-like CD1d-restricted NKT cells in the host defense against HIV-1.
Authors:
Markus Moll; Sofia K Andersson; Anna Smed-Sörensen; Johan K Sandberg
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-08
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-17     Completed Date:  2010-10-29     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1876-84     Citation Subset:  AIM; IM    
Affiliation:
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. markus.moll@ki.se
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MeSH Terms
Descriptor/Qualifier:
Antigen Presentation / immunology*
Antigens, CD1 / metabolism
Antigens, CD1d / genetics,  immunology*,  metabolism
Blotting, Western
Cell Line
Cell Membrane / immunology,  metabolism
Cells, Cultured
Dendritic Cells / immunology*,  metabolism,  virology
Endocytosis / immunology
Endosomes / immunology*,  metabolism
Green Fluorescent Proteins / genetics,  metabolism
HIV-1 / genetics,  immunology,  metabolism
Human Immunodeficiency Virus Proteins / genetics,  immunology*,  metabolism
Humans
Lipids / immunology
Lymphocyte Activation / immunology
Microscopy, Fluorescence
Natural Killer T-Cells / immunology,  metabolism
Protein Binding
Viral Regulatory and Accessory Proteins / genetics,  immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
AI52731/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD1; 0/Antigens, CD1d; 0/Human Immunodeficiency Virus Proteins; 0/Lipids; 0/Viral Regulatory and Accessory Proteins; 0/vpu protein, Human immunodeficiency virus 1; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

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