Open AccessThe Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Author(s) -
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 Kadie,
Jonathan M. Carlson,
David Heckerman,
Robert Graham,
Robert M. Plenge,
Steven G. Deeks,
Lauren Gianniny,
Gabriel Crawford,
Jordan Sullivan,
Elena González,
Leela Davies,
Amy L. Camargo,
Jamie Moore,
Nicole Beattie,
Supriya Gupta,
Andrew Crenshaw,
Noël P. Burtt,
Candace Guiducci,
Namrata Gupta,
Xiaojiang Gao,
Qi Ying,
Yuko Yuki,
Alicja PiechockaTrocha,
Emily Cutrell,
Rachel Rosenberg,
Kristin Moss,
Paul Lemay,
Jessica O'Leary,
Todd M. Schaefer,
Pranshu Verma,
Ildikó Tóth,
Brian L. Block,
B.M. Baker,
Alissa C. 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 Shikuma,
Richard Haubrich,
Sharon A. Riddler,
Paul E. Sax,
Eric S. Daar,
Heather J. Ribaudo,
Brian K. Agan,
Shanu Agarwal,
Richard L Ahern,
Brady Allen,
Sherly Altidor,
Eric Lewin Altschuler,
Sujata Ambardar,
Kathryn Anastos,
Ben Anderson,
Val Anderson,
Ushan Andrady,
Diana Antoniskis,
David R. Bangsberg,
D Barbaro,
W W Barrie,
Jennifer Bartczak,
Simon Barton,
Patricia Basden,
Nesli Basgoz,
Suzane Bazner,
Nicholaos Bellos,
Anne M Benson,
Judith Berger,
Nicole F. Bernard,
Annette M Bernard,
Christopher Birch,
Stanley Bodner,
Robert Bolan,
Emilie T Boudreaux,
Meg Bradley,
J. Braun,
Jon E Brndjar,
Stephen J. Brown,
Katherine A. Brown,
Sheldon T. Brown,
Jedidiah Burack,
Larry M. Bush,
Virginia Cafaro,
Mobola Campbell,
John H. Campbell,
Robert H. Carlson,
J. K. Carmichael,
Kathleen Casey,
Chris Cavacuiti,
Gregory Celestin,
Stephen T. Chambers,
Nancy Chez,
Lisa M Chirch,
Paul J. Cimoch,
Dani Cohen,
L. Cohn,
Brian E. Conway,
David A. Cooper,
Brian M. Cornelson,
David T Cox,
Michael V Cristofano,
G J Cuchural,
Julie Czartoski,
Joseph M Dahman,
Jennifer S. Daly,
Benjamin T. Davis,
Kristine Davis,
Sheila M Davod,
Edwin DeJesus,
Craig Dietz,
Eleanor Dunham,
Michael E. Dunn,
Todd B. Ellerin,
Joseph J. Eron,
John Fangman,
Claire E Farel,
Helen Ferlazzo,
Sarah Fidler,
Anita Fleenor-Ford,
Renee Frankel,
Kenneth A. Freedberg,
Neel K French,
Jonathan D. Fuchs,
Jon Fuller,
Jonna Gaberman,
Joel E. Gallant,
Rajesh T. Gandhi,
Efrain Garcia,
Donald Garmon,
Joseph Gathe,
Cyril R. Gaultier,
Wondwoosen Gebre,
Frank D Gilman,
Ian Gilson,
Paul Goepfert,
Michael S. Gottlieb,
Claudia Goulston,
Richard K. Groger,
TC Gurley,
Stuart Haber,
Robin L. Hardwicke,
William D. Hardy,
P. Richard Harrigan,
Trevor Hawkins,
Sonya L. Heath,
Frederick Hecht,
W. Keith Henry,
Melissa Hladek,
Robert P. Hoffman,
James M. Horton,
Ricky K Hsu,
Gregory Huhn,
Peter W. Hunt,
Mark J Hupert,
Mark L Illeman,
Hans Jaeger,
Robert M. Jellinger,
M. Anne St John,
Jennifer Johnson,
Kristin L. Johnson,
Heather E. Johnson,
Kay M. Johnson,
J Joly,
Wilbert Jordan,
Carol A. Kauffman,
Homayoon Khanlou,
Robert K Killian,
Arthur Y. Kim,
David Kim,
Clifford 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 Lee,
Jean M L Lee,
Marah J Lee,
E 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 Martin,
Kenneth H. Mayer,
M. Juliana McElrath,
Theresa A McGhee,
Barbara McGovern,
Katherine McGowan,
D. E. Mc McIntyre,
Gavin X. McLeod,
Prema Menezes,
Greg Mesa,
Craig E. Metroka,
Dirk MeyerOlson,
Andy O. Miller,
Kate Montgomery,
Karam Mounzer,
Ellen H. Nagami,
Iris Nagin,
Ronald Nahass,
Margret O. Nelson,
Craig Nielsen,
David L Norene,
David H. O’Connor,
Bisola O. Ojikutu,
Jason F. Okulicz,
Olakunle O Oladehin,
Edward C. Oldfield,
Susan Olender,
Mario Ostrowski,
William F. Owen,
Eunice Pae,
Julie Parsonnet,
Andrew M Pavlatos,
A. Perlmutter,
Michael N Pierce,
Jonathan M Pincus,
Leandro Pisani,
Lawrence Jay Price,
Laurie A. Proia,
Richard C. Prokesch,
Heather Calderon Pujet,
Moti Ramgopal,
Almas Rathod,
Michael Rausch,
Jayashree Ravishankar,
Frank S. Rhame,
Constance Shamuyarira Richards,
Douglas D. Richman,
Berta Rodés,
Milagros Rodriguez,
Richard C. Rose,
Eric Rosenberg,
Daniel C. Rosenthal,
Polly E Ross,
David Rubin,
Elease Rumbaugh,
Luis Sáenz-Carbonell,
Michelle Salvaggio,
William C. Sanchez,
Veeraf M. Sanjana,
Steven Santiago,
Wolfgang Schmidt,
Hanneke Schuitemaker,
P Sestak,
Peter Shalit,
William Shay,
Vivian Shirvani,
Vanessa I Silebi,
James M. Sizemore,
Paul R. Skolnik,
Marcia L. Sokol-Anderson,
James M. Sosman,
Paul Stabile,
Jack T. Stapleton,
Sheree Starrett,
F. Stein,
HansJürgen Stellbrink,
F. Lisa Sterman,
Valerie E. Stone,
David R. Stone,
Giuseppe Tambussi,
Randy Taplitz,
Ellen Tedaldi,
W Theisen,
Richard Torres,
Lorraine Tosiello,
Cécile Tremblay,
Marc Tribble,
Phuong D Trinh,
Alice Tsao,
Peggy Ueda,
A Vaccaro,
Emília Valadas,
Thanes Vanig,
Isabel Vecino,
Vilma M Vega,
Wenoah Veikley,
B Wade,
Charles Walworth,
Chingchai Wanidworanun,
Douglas Ward,
Daniel A. Warner,
R. David Weber,
Duncan Webster,
Steve Weis,
David A. Wheeler,
David J. White,
Ed Wilkins,
Alan Winston,
Clifford G. Wlodaver,
Angélique B. van ’t Wout,
David P. Wright,
Otto O. Yang,
David L. Yurdin,
Brandon W Zabukovic,
Kimon C. Zachary,
Beth Zeeman,
Meng Zhao
Publication year - 2010
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.1195271
Subject(s) - human leukocyte antigen , affect (linguistics) , human immunodeficiency virus (hiv) , peptide , presentation (obstetrics) , immunology , genetics , biology , medicine , virology , antigen , psychology , biochemistry , communication , radiology
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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