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 - Agan, Brian
AU - Okulicz, Jason
N1 - Funding Information:
This work was supported by the National Science and Technology Major Project of China (2017ZX10201302-006), Sanming Project, Shenzhen (SZSM201611030) and Shenzhen Project for Technical Breakthrough, Shenzhen, China (JSGG20170413142559220).
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.
UR - http://www.scopus.com/inward/record.url?scp=78650084232&partnerID=8YFLogxK
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 -