Science, Vol.330, No.6010, 1551-1557, 2010
The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Pereyra FP ,
Jia XM ,
McLaren PJ ,
Telenti A ,
de Bakker PIW ,
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 ,
Carrington M ,
Gao XJ ,
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 DML ,
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 ,
Deeks SG ,
DeJesus E ,
Dietz CA ,
Dunham E ,
Dunn ME ,
Ellerin TB ,
Eron JJ ,
Fangman JJW ,
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 T ,
Kurisu W ,
Kwon DS ,
LaMar M ,
Lampiris H ,
Lanzafame M ,
Lederman MM ,
Lee DM ,
Lee JML ,
Lee MJ ,
Lee ETY ,
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 ,
Robbins GK ,
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
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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