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PMID: 21051598 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 330 ·No. 6010 ·2010-12-10 ·Pages 1551-7

International HIV Controllers Study, Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, Ripke S, Brumme CJ, Pulit SL, Carrington M, Kadie CM, Carlson JM, Heckerman D, Graham RR, Plenge RM, Deeks SG, Gianniny L, Crawford G, Sullivan J, Gonzalez E, Davies L, Camargo A, Moore JM, Beattie N, Gupta S, Crenshaw A, Burtt NP, Guiducci C, Gupta N, Gao X, Qi Y, Yuki Y, Piechocka-Trocha A, Cutrell E, Rosenberg R, Moss KL, Lemay P, O'Leary J, Schaefer T, Verma P, Toth I, Block B, Baker B, Rothchild A, Lian J, Proudfoot J, Alvino DM, Vine S, Addo MM, Allen TM, Altfeld M, Henn MR, Le Gall S, Streeck H, Haas DW, Kuritzkes DR, Robbins GK, Shafer RW, Gulick RM, Shikuma CM, Haubrich R, Riddler S, Sax PE, Daar ES, Ribaudo HJ, Agan B, Agarwal S, Ahern RL, Allen BL, Altidor S, Altschuler EL, Ambardar S, Anastos K, Anderson B, Anderson V, Andrady U, Antoniskis D, Bangsberg D, Barbaro D, Barrie W, Bartczak J, Barton S, Basden P, Basgoz N, Bazner S, Bellos NC, Benson AM, Berger J, Bernard NF, Bernard AM, Birch C, Bodner SJ, Bolan RK, Boudreaux ET, Bradley M, Braun JF, Brndjar JE, Brown SJ, Brown K, Brown ST, Burack J, Bush LM, Cafaro V, Campbell O, Campbell J, Carlson RH, Carmichael JK, Casey KK, Cavacuiti C, Celestin G, Chambers ST, Chez N, Chirch LM, Cimoch PJ, Cohen D, Cohn LE, Conway B, Cooper DA, Cornelson B, Cox DT, Cristofano MV, Cuchural G, Czartoski JL, Dahman JM, Daly JS, Davis BT, Davis K, Davod SM, DeJesus E, Dietz CA, Dunham E, Dunn ME, Ellerin TB, Eron JJ, Fangman JJ, Farel CE, Ferlazzo H, Fidler S, Fleenor-Ford A, Frankel R, Freedberg KA, French NK, Fuchs JD, Fuller JD, Gaberman J, Gallant JE, Gandhi RT, Garcia E, Garmon D, Gathe JC, Gaultier CR, Gebre W, Gilman FD, Gilson I, Goepfert PA, Gottlieb MS, Goulston C, Groger RK, Gurley TD, Haber S, Hardwicke R, Hardy WD, Harrigan PR, Hawkins TN, Heath S, Hecht FM, Henry WK, Hladek M, Hoffman RP, Horton JM, Hsu RK, Huhn GD, Hunt P, Hupert MJ, Illeman ML, Jaeger H, Jellinger RM, John M, Johnson JA, Johnson KL, Johnson H, Johnson K, Joly J, Jordan WC, Kauffman CA, Khanlou H, Killian RK, Kim AY, Kim DD, Kinder CA, Kirchner JT, Kogelman L, Kojic EM, Korthuis PT, Kurisu W, Kwon DS, LaMar M, Lampiris H, Lanzafame M, Lederman MM, Lee DM, Lee JM, Lee MJ, Lee ET, Lemoine J, Levy JA, Llibre JM, Liguori MA, Little SJ, Liu AY, Lopez AJ, Loutfy MR, Loy D, Mohammed DY, Man A, Mansour MK, Marconi VC, Markowitz M, Marques R, Martin JN, Martin HL, Mayer KH, McElrath MJ, McGhee TA, McGovern BH, McGowan K, McIntyre D, Mcleod GX, Menezes P, Mesa G, Metroka CE, Meyer-Olson D, Miller AO, Montgomery K, Mounzer KC, Nagami EH, Nagin I, Nahass RG, Nelson MO, Nielsen C, Norene DL, O'Connor DH, Ojikutu BO, Okulicz J, Oladehin OO, Oldfield EC, Olender SA, Ostrowski M, Owen WF, Pae E, Parsonnet J, Pavlatos AM, Perlmutter AM, Pierce MN, Pincus JM, Pisani L, Price LJ, Proia L, Prokesch RC, Pujet HC, Ramgopal M, Rathod A, Rausch M, Ravishankar J, Rhame FS, Richards CS, Richman DD, Rodes B, Rodriguez M, Rose RC, Rosenberg ES, Rosenthal D, Ross PE, Rubin DS, Rumbaugh E, Saenz L, Salvaggio MR, Sanchez WC, Sanjana VM, Santiago S, Schmidt W, Schuitemaker H, Sestak PM, Shalit P, Shay W, Shirvani VN, Silebi VI, Sizemore JM, Skolnik PR, Sokol-Anderson M, Sosman JM, Stabile P, Stapleton JT, Starrett S, Stein F, Stellbrink HJ, Sterman FL, Stone VE, Stone DR, Tambussi G, Taplitz RA, Tedaldi EM, Telenti A, Theisen W, Torres R, Tosiello L, Tremblay C, Tribble MA, Trinh PD, Tsao A, Ueda P, Vaccaro A, Valadas E, Vanig TJ, Vecino I, Vega VM, Veikley W, Wade BH, Walworth C, Wanidworanun C, Ward DJ, Warner DA, Weber RD, Webster D, Weis S, Wheeler DA, White DJ, Wilkins E, Winston A, Wlodaver CG, van't Wout A, Wright DP, Yang OO, Yurdin DL, Zabukovic BW, Zachary KC, Zeeman B, Zhao M

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.

MeSH Terms
African Americans/genetics Alleles Amino Acids/physiology Antigen Presentation CD8-Positive T-Lymphocytes/immunology Cohort Studies Disease Progression Genes, MHC Class I Genome-Wide Association Study HIV Antigens/immunology HIV Infections/ethnology,genetics,immunology,virology HIV Long-Term Survivors HIV-1/immunology HLA-A Antigens/chemistry,genetics,immunology,metabolism HLA-B Antigens/chemistry,genetics,immunology,metabolism HLA-C Antigens/chemistry,genetics,immunology,metabolism Haplotypes Hispanic or Latino/genetics Humans Immunity, Innate Logistic Models Models, Molecular Polymorphism, Single Nucleotide Protein Conformation Viral Load Whites/genetics
Chemicals
Amino Acids HIV Antigens HLA-A Antigens HLA-B Antigens HLA-C Antigens
Authors & Affiliations
339 authors, click to expand affiliations / ORCID
International HIV Controllers Study
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.
Pereyra Florencia
Jia Xiaoming
McLaren Paul J
Telenti Amalio
de Bakker Paul I W
Walker Bruce D
Ripke Stephan
Brumme Chanson J
Pulit Sara L
Carrington Mary
Kadie Carl M
Carlson Jonathan M
Heckerman David
Graham Robert R
Plenge Robert M
Deeks Steven G
Gianniny Lauren
Crawford Gabriel
Sullivan Jordan
Gonzalez Elena
Davies Leela
Camargo Amy
Moore Jamie M
Beattie Nicole
Gupta Supriya
Crenshaw Andrew
Burtt Noël P
Guiducci Candace
Gupta Namrata
Gao Xiaojiang
Qi Ying
Yuki Yuko
Piechocka-Trocha Alicja
Cutrell Emily
Rosenberg Rachel
Moss Kristin L
Lemay Paul
O'Leary Jessica
Schaefer Todd
Verma Pranshu
Toth Ildiko
Block Brian
Baker Brett
Rothchild Alissa
Lian Jeffrey
Proudfoot Jacqueline
Alvino Donna Marie L
Vine Seanna
Addo Marylyn M
Allen Todd M
Altfeld Marcus
Henn Matthew R
Le Gall Sylvie
Streeck Hendrik
Haas David W
Kuritzkes Daniel R
Robbins Gregory K
Shafer Robert W
Gulick Roy M
Shikuma Cecilia M
Haubrich Richard
Riddler Sharon
Sax Paul E
Daar Eric S
Ribaudo Heather J
Agan Brian
Agarwal Shanu
Ahern Richard L
Allen Brady L
Altidor Sherly
Altschuler Eric L
Ambardar Sujata
Anastos Kathryn
Anderson Ben
Anderson Val
Andrady Ushan
Antoniskis Diana
Bangsberg David
Barbaro Daniel
Barrie William
Bartczak J
Barton Simon
Basden Patricia
Basgoz Nesli
Bazner Suzane
Bellos Nicholaos C
Benson Anne M
Berger Judith
Bernard Nicole F
Bernard Annette M
Birch Christopher
Bodner Stanley J
Bolan Robert K
Boudreaux Emilie T
Bradley Meg
Braun James F
Brndjar Jon E
Brown Stephen J
Brown Katherine
Brown Sheldon T
Burack Jedidiah
Bush Larry M
Cafaro Virginia
Campbell Omobolaji
Campbell John
Carlson Robert H
Carmichael J Kevin
Casey Kathleen K
Cavacuiti Chris
Celestin Gregory
Chambers Steven T
Chez Nancy
Chirch Lisa M
Cimoch Paul J
Cohen Daniel
Cohn Lillian E
Conway Brian
Cooper David A
Cornelson Brian
Cox David T
Cristofano Michael V
Cuchural George
Czartoski Julie L
Dahman Joseph M
Daly Jennifer S
Davis Benjamin T
Davis Kristine
Davod Sheila M
DeJesus Edwin
Dietz Craig A
Dunham Eleanor
Dunn Michael E
Ellerin Todd B
Eron Joseph J
Fangman John J W
Farel Claire E
Ferlazzo Helen
Fidler Sarah
Fleenor-Ford Anita
Frankel Renee
Freedberg Kenneth A
French Neel K
Fuchs Jonathan D
Fuller Jon D
Gaberman Jonna
Gallant Joel E
Gandhi Rajesh T
Garcia Efrain
Garmon Donald
Gathe Joseph C
Gaultier Cyril R
Gebre Wondwoosen
Gilman Frank D
Gilson Ian
Goepfert Paul A
Gottlieb Michael S
Goulston Claudia
Groger Richard K
Gurley T Douglas
Haber Stuart
Hardwicke Robin
Hardy W David
Harrigan P Richard
Hawkins Trevor N
Heath Sonya
Hecht Frederick M
Henry W Keith
Hladek Melissa
Hoffman Robert P
Horton James M
Hsu Ricky K
Huhn Gregory D
Hunt Peter
Hupert Mark J
Illeman Mark L
Jaeger Hans
Jellinger Robert M
John Mina
Johnson Jennifer A
Johnson Kristin L
Johnson Heather
Johnson Kay
Joly Jennifer
Jordan Wilbert C
Kauffman Carol A
Khanlou Homayoon
Killian Robert K
Kim Arthur Y
Kim David D
Kinder Clifford A
Kirchner Jeffrey T
Kogelman Laura
Kojic Erna Milunka
Korthuis P Todd
Kurisu Wayne
Kwon Douglas S
LaMar Melissa
Lampiris Harry
Lanzafame Massimiliano
Lederman Michael M
Lee David M
Lee Jean M L
Lee Marah J
Lee Edward T Y
Lemoine Janice
Levy Jay A
Llibre Josep M
Liguori Michael A
Little Susan J
Liu Anne Y
Lopez Alvaro J
Loutfy Mono R
Loy Dawn
Mohammed Debbie Y
Man Alan
Mansour Michael K
Marconi Vincent C
Markowitz Martin
Marques Rui
Martin Jeffrey N
Martin Harold L
Mayer Kenneth Hugh
McElrath M Juliana
McGhee Theresa A
McGovern Barbara H
McGowan Katherine
McIntyre Dawn
Mcleod Gavin X
Menezes Prema
Mesa Greg
Metroka Craig E
Meyer-Olson Dirk
Miller Andy O
Montgomery Kate
Mounzer Karam C
Nagami Ellen H
Nagin Iris
Nahass Ronald G
Nelson Margret O
Nielsen Craig
Norene David L
O'Connor David H
Ojikutu Bisola O
Okulicz Jason
Oladehin Olakunle O
Oldfield Edward C
Olender Susan A
Ostrowski Mario
Owen William F
Pae Eunice
Parsonnet Jeffrey
Pavlatos Andrew M
Perlmutter Aaron M
Pierce Michael N
Pincus Jonathan M
Pisani Leandro
Price Lawrence Jay
Proia Laurie
Prokesch Richard C
Pujet Heather Calderon
Ramgopal Moti
Rathod Almas
Rausch Michael
Ravishankar J
Rhame Frank S
Richards Constance Shamuyarira
Richman Douglas D
Rodes Berta
Rodriguez Milagros
Rose Richard C
Rosenberg Eric S
Rosenthal Daniel
Ross Polly E
Rubin David S
Rumbaugh Elease
Saenz Luis
Salvaggio Michelle R
Sanchez William C
Sanjana Veeraf M
Santiago Steven
Schmidt Wolfgang
Schuitemaker Hanneke
Sestak Philip M
Shalit Peter
Shay William
Shirvani Vivian N
Silebi Vanessa I
Sizemore James M
Skolnik Paul R
Sokol-Anderson Marcia
Sosman James M
Stabile Paul
Stapleton Jack T
Starrett Sheree
Stein Francine
Stellbrink Hans-Jurgen
Sterman F Lisa
Stone Valerie E
Stone David R
Tambussi Giuseppe
Taplitz Randy A
Tedaldi Ellen M
Telenti Amalio
Theisen William
Torres Richard
Tosiello Lorraine
Tremblay Cecile
Tribble Marc A
Trinh Phuong D
Tsao Alice
Ueda Peggy
Vaccaro Anthony
Valadas Emilia
Vanig Thanes J
Vecino Isabel
Vega Vilma M
Veikley Wenoah
Wade Barbara H
Walworth Charles
Wanidworanun Chingchai
Ward Douglas J
Warner Daniel A
Weber Robert D
Webster Duncan
Weis Steve
Wheeler David A
White David J
Wilkins Ed
Winston Alan
Wlodaver Clifford G
van't Wout Angelique
Wright David P
Yang Otto O
Yurdin David L
Zabukovic Brandon W
Zachary Kimon C
Zeeman Beth
Zhao Meng
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1195271
Published
2010-12-10
Epub
2010-00-04
Pages
1551-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3235490
Subset
IM
Grants
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NIAID NIH HHS · R24 AI067039-06 · United States
NIAID NIH HHS · U01 AI034853 · United States
NIAID NIH HHS · R37 AI028568 · United States
NIAID NIH HHS · R01 AI087145-01 · United States
NIAID NIH HHS · U01 AI069434-05 · United States
NIAID NIH HHS · UM1 AI069452 · United States
NIAID NIH HHS · U01 AI069428-05 · United States
NIAID NIH HHS · AI069424 · United States
NIAID NIH HHS · AI087145 · United States
NIAID NIH HHS · UM1 AI069496 · United States
NIAID NIH HHS · U01 AI069415 · United States
NCRR NIH HHS · UL1 RR024131-07 · United States
NIAID NIH HHS · U01 AI069428-06 · United States
NIAID NIH HHS · U01 AI038844-04 · United States
NIAID NIH HHS · U01 AI069495 · United States
Intramural NIH HHS · United States
NIAID NIH HHS · UM1 AI069556 · United States
NIAID NIH HHS · P30 AI027763 · United States
NIAID NIH HHS · U01 AI038844-04S3 · United States
NIAID NIH HHS · U01 AI069511 · United States
NIAID NIH HHS · U01 AI069432-06 · United States
NIDA NIH HHS · K23 DA019809 · United States
NIAID NIH HHS · UM1 AI068636-07 · United States
NIAID NIH HHS · U01 AI069532-06 · United States
NIAID NIH HHS · U01 AI069502-05 · United States
NIAID NIH HHS · U01 AI069532-05 · United States
NIAID NIH HHS · U01 AI038844-04S1 · United States
NIMH NIH HHS · R01 MH071205 · United States
NIAID NIH HHS · UM1 AI069502 · United States
NIAID NIH HHS · UM1 AI069450 · United States
NIAID NIH HHS · AI34835 · United States
NIAID NIH HHS · U01 AI025859 · United States
NIAID NIH HHS · UM1 AI068636-06 · United States
NIMH NIH HHS · MH071205 · United States
NIAID NIH HHS · UM1 AI069532 · United States
NIMH NIH HHS · R01 MH071205-05 · United States
NIAID NIH HHS · R01 AI087145-02 · United States
NCRR NIH HHS · UL1 RR024975 · United States
NIAID NIH HHS · U01 AI069424 · United States
NIAID NIH HHS · UM1 AI069465 · United States
PHS HHS · AL32782 · United States
NIAID NIH HHS · K24 AI064086-05 · United States
NIAID NIH HHS · AI069450 · United States
NIAID NIH HHS · U01 AI034853-12 · United States
CCR NIH HHS · HHSN261200800001C · United States
NIAID NIH HHS · AI069472 · United States
NIAID NIH HHS · UM1 AI069419 · United States
NIAID NIH HHS · AI28568 · United States
NIAID NIH HHS · U01 AI069471-05 · United States
NIAID NIH HHS · AI069432 · United States
NIAID NIH HHS · P30 AI027763-20 · United States
NIAID NIH HHS · U01 AI069502-06 · United States
NIAID NIH HHS · U01 AI069477 · United States
NIAID NIH HHS · U01 AI069424-06 · United States
NIAID NIH HHS · R01 AI077505-04 · United States
NIAID NIH HHS · UM1 AI068634-07 · United States
NIAID NIH HHS · R01 AI028568 · United States
NIAID NIH HHS · U01 AI069474-06 · United States
NIAID NIH HHS · P30 AI060354 · United States
NIAID NIH HHS · U01 AI069495-05 · United States
NIAID NIH HHS · U01 AI069419 · United States
NIAID NIH HHS · R01 AI030914 · United States
NIAID NIH HHS · AI25859 · United States
NIAID NIH HHS · UM1 AI069511 · United States
NCI NIH HHS · HHSN261200800001E · United States
NIAID NIH HHS · U01 AI069452 · United States
NIAID NIH HHS · UM1 AI069467 · United States
NIAID NIH HHS · U01 AI027661-18 · United States
NIAID NIH HHS · U01 AI069434-06 · United States
NIAID NIH HHS · AI38844 · United States
NIAID NIH HHS · P30 AI060354-08 · United States
NIAID NIH HHS · U01 AI069432-05 · United States
NIAID NIH HHS · R01 AI030914-16 · United States
NIAID NIH HHS · AI069477 · United States
NIAID NIH HHS · U01 AI069472-05 · United States
NIAID NIH HHS · AI069471 · United States
NIAID NIH HHS · U01 AI069471 · United States
NIAID NIH HHS · U01 AI069472 · United States
NIAID NIH HHS · P30 AI050410 · United States
NIAID NIH HHS · R24 AI106039 · United States
NIAID NIH HHS · U01 AI068634 · United States
NIAID NIH HHS · UM1 AI068636 · United States
Corrections
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PMID: 21148380
External Links
PubMed source DOI: 10.1126/science.1195271 PMC Full Text View journal details
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