TY - JOUR
T1 - The major genetic determinants of HIV-1 control affect HLA class I peptide presentation
AU - The International HIV Controllers Study
AU - Pereyra, Florencia
AU - Jia, Xiaoming
AU - McLaren, Paul J.
AU - Telenti, Amalio
AU - de Bakker, Paul I.W.
AU - Walker, Bruce D.
AU - Ripke, Stephan
AU - Brumme, Chanson J.
AU - Pulit, Sara L.
AU - Carrington, Mary
AU - Kadie, Carl M.
AU - Carlson, Jonathan M.
AU - Heckerman, David
AU - Graham, Robert R.
AU - Plenge, Robert M.
AU - Deeks, Steven G.
AU - Gianniny, Lauren
AU - Crawford, Gabriel
AU - Sullivan, Jordan
AU - Gonzalez, Elena
AU - Davies, Leela
AU - Camargo, Amy
AU - Moore, Jamie M.
AU - Beattie, Nicole
AU - Gupta, Supriya
AU - Crenshaw, Andrew
AU - Burtt, Noël P.
AU - Guiducci, Candace
AU - Gupta, Namrata
AU - Gao, Xiaojiang
AU - Qi, Ying
AU - Yuki, Yuko
AU - Piechocka-Trocha, Alicja
AU - Cutrell, Emily
AU - Rosenberg, Rachel
AU - Moss, Kristin L.
AU - Lemay, Paul
AU - O’leary, Jessica
AU - Schaefer, Todd
AU - Verma, Pranshu
AU - Toth, Ildiko
AU - Block, Brian
AU - Baker, Brett
AU - Rothchild, Alissa
AU - Lian, Jeffrey
AU - Proudfoot, Jacqueline
AU - Alvino, Donna Marie L.
AU - Vine, Seanna
AU - Addo, Marylyn M.
AU - Hladek, Melissa
N1 - Funding Information:
The support of the ARO (DAAD19-01-1-0486 and DAAD 19-02-1-0245) and the DFG (GW, WI 1899/1-1) is most gratefully acknowledged. T. Jaster is thanked for skilled assistance in the tedious, but important nanocrystal size distribution measurements, Dr. H. Rösner is thanked for his TEM work on the Al–Sm ribbons and Dr. S. Kim is thanked for the thermodynamic calculations.
PY - 2010/12/10
Y1 - 2010/12/10
N2 - 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.
AB - 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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U2 - 10.1126/science.1195271
DO - 10.1126/science.1195271
M3 - Article
C2 - 21051598
AN - SCOPUS:78650084232
SN - 0036-8075
VL - 330
SP - 1551
EP - 1557
JO - Science
JF - Science
IS - 6010
ER -