The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

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Auteurs

Date

2010

Discipline

Anthropologie biologique

Type de document

Articles

Périmètre

Publications

Langue

Anglais

Identifiants

doi: 10.1126/science.1195271
issn: 0036-8075

Source

Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1126/science.1195271

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/21051598

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1095-9203

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_7DB03A4B17331

Collection

Serveur Académique Lausannois

Organisation

Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

Mots-clés 0

African Americans/genetics; Alleles; Amino Acids/physiology; Antigen Presentation; CD8-Positive T-Lymphocytes/immunology; Cohort Studies; Disease Progression; European Continental Ancestry Group/genetics; Genes, MHC Class I; Genome-Wide Association Study; HIV Antigens/immunology; HIV Infections/ethnology; HIV Infections/genetics; HIV Long-Term Survivors; HIV-1/immunology; HLA-A Antigens/chemistry; HLA-A Antigens/genetics; HLA-B Antigens/chemistry; HLA-B Antigens/genetics; HLA-C Antigens/chemistry; HLA-C Antigens/genetics; Haplotypes; Hispanic Americans/genetics; Humans; Immunity, Innate; Logistic Models; Models, Molecular; Polymorphism, Single Nucleotide; Protein Conformation; Viral Load

Sujets proches En

Group dynamics Association Groups, Social Infectious diseases

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F. Pereyra et al., « The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. », Serveur académique Lausannois, ID : 10.1126/science.1195271

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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.

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