Article ; Online: The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
2010 Volume 330, Issue 6010, Page(s) 1551–1557
Abstract: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a ... ...
Abstract | Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection. |
||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
MeSH term(s) | Black or African American/genetics ; Alleles ; Amino Acids/physiology ; Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Disease Progression ; Genes, MHC Class I ; Genome-Wide Association Study ; HIV Antigens/immunology ; HIV Infections/ethnology ; HIV Infections/genetics ; HIV Infections/immunology ; HIV Infections/virology ; HIV Long-Term Survivors ; HIV-1/immunology ; HLA-A Antigens/chemistry ; HLA-A Antigens/genetics ; HLA-A Antigens/immunology ; HLA-A Antigens/metabolism ; HLA-B Antigens/chemistry ; HLA-B Antigens/genetics ; HLA-B Antigens/immunology ; HLA-B Antigens/metabolism ; HLA-C Antigens/chemistry ; HLA-C Antigens/genetics ; HLA-C Antigens/immunology ; HLA-C Antigens/metabolism ; Haplotypes ; Hispanic or Latino/genetics ; Humans ; Immunity, Innate ; Logistic Models ; Models, Molecular ; Polymorphism, Single Nucleotide ; Protein Conformation ; Viral Load ; White People/genetics | ||||||||||
Chemical Substances | Amino Acids ; HIV Antigens ; HLA-A Antigens ; HLA-B Antigens ; HLA-C Antigens | ||||||||||
Language | English | ||||||||||
Publishing date | 2010-11-04 | ||||||||||
Publishing country | United States | ||||||||||
Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't | ||||||||||
ZDB-ID | 128410-1 | ||||||||||
ISSN | 1095-9203 ; 0036-8075 | ||||||||||
ISSN (online) | 1095-9203 | ||||||||||
ISSN | 0036-8075 | ||||||||||
DOI | 10.1126/science.1195271 | ||||||||||
Shelf mark |
|
||||||||||
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
Zs.A 27: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
|||
Zs.MG 77: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.