Title

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

Authors

Florencia Pereyra
Xiaoming Jia
Paul J McLaren
Amalio Telenti
Paul I W de Bakker
Bruce D Walker
Stephan Ripke
Chanson J Brumme
Sara L Pulit
Mary Carrington
Carl M Kadie
Jonathan M Carlson
David Heckerman
Robert R Graham
Robert M Plenge
Steven G Deeks
Lauren Gianniny
Gabriel Crawford
Jordan Sullivan
Elena Gonzalez
Leela Davies
Amy Camargo
Jamie M Moore
Nicole Beattie
Supriya Gupta
Andrew Crenshaw
Noël P Burtt
Candace Guiducci
Namrata Gupta
Xiaojiang Gao
Ying Qi
Yuko Yuki
Alicja Piechocka-Trocha
Emily Cutrell
Rachel Rosenberg
Kristin L Moss
Paul Lemay
Jessica O'Leary
Todd Schaefer
Pranshu Verma
Ildiko Toth
Brian Block
Brett Baker
Alissa Rothchild
Jeffrey Lian
Jacqueline Proudfoot
Donna Marie L Alvino
Seanna Vine
Marylyn M Addo
Todd M Allen
Marcus Altfeld
Matthew R Henn
Sylvie Le Gall
Hendrik Streeck
David W Haas
Daniel R Kuritzkes
Gregory K Robbins
Robert W Shafer
Roy M Gulick
Cecilia M Shikuma
Richard Haubrich
Sharon Riddler
Paul E Sax
Eric S Daar
Heather J Ribaudo
Brian Agan
Shanu Agarwal
Richard L Ahern
Brady L Allen
Sherly Altidor
Eric L Altschuler
Sujata Ambardar
Kathryn Anastos
Ben Anderson
Val Anderson
Ushan Andrady
Diana Antoniskis
David Bangsberg
Daniel Barbaro
William Barrie
J Bartczak
Simon Barton
Patricia Basden
Nesli Basgoz
Suzane Bazner
Nicholaos C Bellos
Anne M Benson
Judith Berger
Nicole F Bernard
Annette M Bernard
Christopher Birch
Stanley J Bodner
Robert K Bolan
Emilie T Boudreaux
Meg Bradley
James F Braun
Jon E Brndjar
Stephen J Brown
Katherine Brown
Sheldon T Brown
Jedidiah Burack
Larry M Bush
Virginia Cafaro
Omobolaji Campbell
John Campbell
Robert H Carlson
J Kevin Carmichael
Kathleen K Casey
Chris Cavacuiti
Gregory Celestin
Steven T Chambers
Nancy Chez
Lisa M Chirch
Paul J Cimoch
Daniel Cohen
Lillian E Cohn
Brian Conway
David A Cooper
Brian Cornelson
David T Cox
Michael V Cristofano
George Cuchural
Julie L Czartoski
Joseph M Dahman
Jennifer S Daly
Benjamin T Davis
Kristine Davis
Sheila M Davod
Edwin DeJesus
Craig A Dietz
Eleanor Dunham
Michael E Dunn
Todd B Ellerin
Joseph J Eron
John J W Fangman
Claire E Farel
Helen Ferlazzo
Sarah Fidler
Anita Fleenor-Ford
Renee Frankel
Kenneth A Freedberg
Neel K French
Jonathan D Fuchs
Jon D Fuller
Jonna Gaberman
Joel E Gallant
Rajesh T Gandhi
Efrain Garcia
Donald Garmon
Joseph C Gathe
Cyril R Gaultier
Wondwoosen Gebre
Frank D Gilman
Ian Gilson
Paul A Goepfert
Michael S Gottlieb
Claudia Goulston
Richard K Groger
T Douglas Gurley
Stuart Haber
Robin Hardwicke
W David Hardy
P Richard Harrigan
Trevor N Hawkins
Sonya Heath
Frederick M Hecht
W Keith Henry
Melissa Hladek
Robert P Hoffman
James M Horton
Ricky K Hsu
Gregory D Huhn
Peter Hunt
Mark J Hupert
Mark L Illeman
Hans Jaeger
Robert M Jellinger
Mina John
Jennifer A Johnson
Kristin L Johnson
Heather Johnson
Kay Johnson
Jennifer Joly
Wilbert C Jordan
Carol A Kauffman
Homayoon Khanlou
Robert K Killian
Arthur Y Kim
David D Kim
Clifford A Kinder
Jeffrey T Kirchner
Laura Kogelman
Erna Milunka Kojic
P Todd Korthuis
Wayne Kurisu
Douglas S Kwon
Melissa LaMar
Harry Lampiris
Massimiliano Lanzafame
Michael M Lederman
David M Lee
Jean M L Lee
Marah J Lee
Edward T Y Lee
Janice Lemoine
Jay A Levy
Josep M Llibre
Michael A Liguori
Susan J Little
Anne Y Liu
Alvaro J Lopez
Mono R Loutfy
Dawn Loy
Debbie Y Mohammed
Alan Man
Michael K Mansour
Vincent C Marconi
Martin Markowitz
Rui Marques
Jeffrey N Martin
Harold L Martin
Kenneth Hugh Mayer
M Juliana McElrath
Theresa A McGhee
Barbara H McGovern
Katherine McGowan
Dawn McIntyre
Gavin X Mcleod
Prema Menezes
Greg Mesa
Craig E Metroka
Dirk Meyer-Olson
Andy O Miller
Kate Montgomery
Karam C Mounzer
Ellen H Nagami
Iris Nagin
Ronald G Nahass
Margret O Nelson
Craig Nielsen
David L Norene
David H O'Connor
Bisola O Ojikutu
Jason Okulicz
Olakunle O Oladehin
Edward C Oldfield
Susan A Olender
Mario Ostrowski
William F Owen
Eunice Pae
Jeffrey Parsonnet
Andrew M Pavlatos
Aaron M Perlmutter
Michael N Pierce
Jonathan M Pincus
Leandro Pisani
Lawrence Jay Price
Laurie Proia
Richard C Prokesch
Heather Calderon Pujet
Moti Ramgopal
Almas Rathod
Michael Rausch
J Ravishankar
Frank S Rhame
Constance Shamuyarira Richards
Douglas D Richman
Berta Rodes
Milagros Rodriguez
Richard C Rose
Eric S Rosenberg
Daniel Rosenthal
Polly E Ross
David S Rubin
Elease Rumbaugh
Luis Saenz
Michelle R Salvaggio
William C Sanchez
Veeraf M Sanjana
Steven Santiago
Wolfgang Schmidt
Hanneke Schuitemaker
Philip M Sestak
Peter Shalit
William Shay
Vivian N Shirvani
Vanessa I Silebi
James M Sizemore
Paul R Skolnik
Marcia Sokol-Anderson
James M Sosman
Paul Stabile
Jack T Stapleton
Sheree Starrett
Francine Stein
Hans-Jurgen Stellbrink
F Lisa Sterman
Valerie E Stone
David R Stone
Giuseppe Tambussi
Randy A Taplitz
Ellen M Tedaldi
Amalio Telenti
William Theisen
Richard Torres
Lorraine Tosiello
Cecile Tremblay
Marc A Tribble
Phuong D Trinh
Alice Tsao
Peggy Ueda
Anthony Vaccaro
Emilia Valadas
Thanes J Vanig
Isabel Vecino
Vilma M Vega
Wenoah Veikley
Barbara H Wade
Charles Walworth
Chingchai Wanidworanun
Douglas J Ward
Daniel A Warner
Robert D Weber
Duncan Webster
Steve Weis
David A Wheeler
David J White
Ed Wilkins
Alan Winston
Clifford G Wlodaver
Angelique van't Wout
David P Wright
Otto O Yang
David L Yurdin
Brandon W Zabukovic
Kimon C Zachary
Beth Zeeman
Meng Zhao

Publication/Presentation Date

12-10-2010

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.

Volume

330

Issue

6010

First Page

1551

Last Page

1557

ISSN

1095-9203

Disciplines

Medicine and Health Sciences

PubMedID

21051598

Department(s)

Department of Medicine

Document Type

Article

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