| Counteraction of HLA-C-mediated immune control of HIV-1 by Nef. | |
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MedLine Citation:
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PMID: 20463068 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A host genetic variant (-35C/T) correlates with increased human leukocyte antigen C (HLA-C) expression and improved control of HIV-1. HLA-C-mediated immunity may be particularly protective because HIV-1 is unable to remove HLA-C from the cell surface, whereas it can avoid HLA-A- and HLA-B-mediated immunity by Nef-mediated down-modulation. However, some individuals with the protective -35CC genotype exhibit high viral loads. Here, we investigated whether the ability of HIV-1 to replicate efficiently in the "protective" high-HLA-C-expression host environment correlates with specific functional properties of Nef. We found that high set point viral loads (sVLs) were not associated with the emergence of Nef variants that had acquired the ability to down-modulate HLA-C or were more effective in removing HLA-A and HLA-B from the cell surface. However, in individuals with the protective -35CC genotype we found a significant association between sVLs and the efficiency of Nef-mediated enhancement of virion infectivity and modulation of CD4, CD28, and the major histocompatibility complex class II (MHC-II)-associated invariant chain (Ii), while this was not observed in subjects with the -35TT genotype. Since the latter Nef functions all influence the stimulation of CD4(+) T helper cells by antigen-presenting cells, they may cooperate to affect both the activation status of infected T cells and the generation of an antiviral cytotoxic T-lymphocyte (CTL) response. In comparison, different levels of viremia in individuals with the common -35TT genotype were not associated with differences in Nef function but with differences in HLA-C mRNA expression levels. Thus, while high HLA-C expression may generally facilitate control of HIV-1, Nef may counteract HLA-C-mediated immune control in some individuals indirectly, by manipulating T-cell function and MHC-II antigen presentation. |
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Authors:
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Anke Specht; Amalio Telenti; Raquel Martinez; Jacques Fellay; Elizabeth Bailes; David T Evans; Mary Carrington; Beatrice H Hahn; David B Goldstein; Frank Kirchhoff |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2010-05-12 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-21 Completed Date: 2010-08-11 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 7300-11 Citation Subset: IM |
Affiliation:
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Institute of Molecular Virology, University Hospital of Ulm, Meyerhofstr. 1, 89081 Ulm, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD8
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genetics,
immunology Cell Line Genotype HIV-1 / immunology* HLA-C Antigens / genetics, immunology* Histocompatibility Antigens Class I / genetics, immunology Histocompatibility Antigens Class II / genetics, immunology Humans NFATC Transcription Factors / genetics, metabolism Polymorphism, Genetic Recombinant Fusion Proteins / genetics, metabolism Viral Load nef Gene Products, Human Immunodeficiency Virus / genetics, immunology, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AI067057/AI/NIAID NIH HHS; AI067854/AI/NIAID NIH HHS; AI63993/AI/NIAID NIH HHS; AI71306/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD8; 0/HLA-C Antigens; 0/Histocompatibility Antigens Class I; 0/Histocompatibility Antigens Class II; 0/NFATC Transcription Factors; 0/Recombinant Fusion Proteins; 0/nef Gene Products, Human Immunodeficiency Virus |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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