The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

被引：920

作者：

Pereyra, Florencia ^{[1
,2
]}

Jia, Xiaoming ^{[3
]}

McLaren, Paul J. ^{[4
,5
]}

Telenti, Amalio ^{[6
]}

de Bakker, Paul I. W. ^{[4
,5
,7
,8
]}

Walker, Bruce D. ^{[1
,9
]}

Ripke, Stephan ^{[4
,10
]}

Brumme, Chanson J. ^{[1
]}

Pulit, Sara L. ^{[4
,5
]}

Carrington, Mary ^{[1
]}

Kadie, Carl M. ^{[12
]}

Carlson, Jonathan M. ^{[13
]}

Heckerman, David ^{[13
]}

Graham, Robert R. ^{[14
]}

Plenge, Robert M. ^{[4
,15
]}

Deeks, Steven G. ^{[16
]}

Gianniny, Lauren ^{[4
]}

Crawford, Gabriel ^{[4
]}

Sullivan, Jordan ^{[4
]}

Gonzalez, Elena ^{[4
]}

Davies, Leela ^{[4
]}

Camargo, Amy ^{[4
]}

Moore, Jamie M. ^{[4
]}

Beattie, Nicole ^{[4
]}

Gupta, Supriya ^{[4
]}

Crenshaw, Andrew ^{[4
]}

Burtt, Noel P. ^{[4
]}

Guiducci, Candace ^{[4
]}

Gupta, Namrata ^{[4
]}

Carrington, Mary ^{[1
]}

Gao, Xiaojiang ^{[11
]}

Qi, Ying ^{[11
]}

Yuki, Yuko ^{[11
]}

Piechocka-Trocha, Alicja ^{[1
]}

Cutrell, Emily ^{[1
]}

Rosenberg, Rachel ^{[1
]}

Moss, Kristin L. ^{[1
]}

Lemay, Paul ^{[1
]}

O'Leary, Jessica ^{[1
]}

Schaefer, Todd ^{[1
]}

Verma, Pranshu ^{[1
]}

Toth, Ildiko ^{[1
]}

Block, Brian ^{[1
]}

Baker, Brett ^{[1
]}

Rothchild, Alissa ^{[1
]}

Lian, Jeffrey ^{[1
]}

Proudfoot, Jacqueline ^{[1
]}

Alvino, Donna Marie L. ^{[1
]}

Vine, Seanna ^{[1
]}

Addo, Marylyn M. ^{[1
]}

机构：

[1] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Regon Inst, Boston, MA USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA 02115 USA

[3] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA

[4] Harvard & MIT, Broad Inst, Cambridge, MA USA

[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA

[6] Univ Lausanne, Inst Microbiol, Lausanne, Switzerland

[7] Univ Med Ctr Utrecht, Dept Med Genet, Div Biomed Genet, Utrecht, Netherlands

[8] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[9] Howard Hughes Med Inst, Chevy Chase, MD USA

[10] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Med, Boston, MA USA

[11] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21701 USA

[12] Microsoft Res, Redmond, WA USA

[13] Microsoft Res, Los Angeles, CA USA

[14] Genentech Inc, San Francisco, CA 94080 USA

[15] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[16] Univ Calif San Francisco, San Francisco, CA 94143 USA

[17] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA

[18] Stanford Univ, Palo Alto, CA 94304 USA

[19] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[20] Univ Hawaii, John A Burns Sch Med, Hawaii Ctr AIDS, Honolulu, HI 96822 USA

[21] Univ Calif San Diego, San Diego, CA 92103 USA

[22] Univ Pittsburgh, Pittsburgh, PA USA

[23] Univ Calif Los Angeles, Los Angeles, CA USA

[24] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[25] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA

[26] Summa Hlth Syst, Akron, OH USA

[27] Uptown Phys Grp, Dallas, TX USA

[28] St Lukes Roosevelt Hosp, New York, NY 10025 USA

[29] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp, Newark, NJ 07103 USA

[30] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA

[31] St Leonards Med Ctr, St Leonards, NSW, Australia

[32] Ysbyty Gwynedd Hosp, Bangor, Gwynedd, Wales

[33] Kaiser Permanente, Portland, OR USA

[34] Tarrant Cty Infect Dis Associates, Ft Worth, TX USA

[35] Rowan Tree Med, Wilton Manors, FL USA

[36] Chelsea & Westminster Hosp, St Stephens Ctr, London, England

[37] SW Infect Dis Associates, Dallas, TX USA

[38] St Barnabas Hosp, Bronx, NY USA

[39] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada

[40] Thacker Thompson & Bernard, Atlanta, GA USA

[41] Vanderbilt Univ, Sch ofMedicine, Hermitage, TN USA

[42] LA Gay & Lesbian Ctr, Los Angeles, CA USA

[43] Louisiana State Univ, Hlth Sci Ctr, Univ Med Ctr E Clin, Lafayatte, LA USA

[44] Callen Lorde Community Hlth Ctr, Phys Res Network, New York, NY USA

[45] Brndjar Med Associates, Allentown, PA USA

[46] AIDS Res Alliance, Los Angeles, CA USA

[47] David Powell Community Hlth Ctr, Austin, TX USA

[48] James J Peters VA Med Ctr, Bronx, NY USA

[49] Sunrise Med Grp, Brooklyn, NY USA

[50] Univ Miami, Miller Sch Med, Lake Worth, FL USA

来源：

SCIENCE | 2010年 / 330卷 / 6010期

基金：

瑞士国家科学基金会;

关键词：

DISEASE PROGRESSION; SURFACE EXPRESSION; INFECTION; AIDS; ALLELES; MHC; RESTRICTION; ASSOCIATION; THERAPY; ABSENCE;

D O I：

10.1126/science.1195271

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1551 / 1557

页数：7

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