A whole-genome association study of major determinants for host control of HIV-1

被引：986

作者：

Fellay, Jacques

Shianna, Kevin V.

Ge, Dongliang

Colombo, Sara

Ledergerber, Bruno

Weale, Mike

Zhang, Kunlin

Gumbs, Curtis

Castagna, Antonella

Cossarizza, Andrea

Cozzi-Lepri, Alessandro

De Luca, Andrea

Easterbrook, Philippa

Francioli, Patrick

Mallal, Simon

Martinez-Picado, Javier

Miro, Jose M.

Obel, Niels

Smith, Jason P.

Wyniger, Josiane

Descombes, Patrick

Antonarakis, Stylianos E.

Letvin, Norman L.

McMichael, Andrew J.

Haynes, Barton F.

Telenti, Amalio ^{[1
]}

Goldstein, David B.

机构：

[1] Univ Hosp Ctr, Inst Microbiol, CH-1011 Lausanne, Switzerland

[2] Univ Lausanne, CH-1011 Lausanne, Switzerland

[3] Duke Univ, Ctr Populat Genom & Pharmacogenet, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA

[4] Univ Zurich Hosp, Div Infect Dis, CH-8091 Zurich, Switzerland

[5] Univ Milan, Osped San Raffaele, Clin Infect Dis, Ist Ricovero & Cura Carattere Sci, I-20127 Milan, Italy

[6] Univ Modena & Reggio Emilia, Sch Med, Dept Biomed Sci, Sect Gen Pathol, I-41100 Modena, Italy

[7] UCL, Dept Primary Care & Populat Sci, Royal Free & Univ Coll Med Sch, London NW3 2PF, England

[8] Univ Cattolica Sacro Cuore, Inst Clin Infect Dis, I-00168 Rome, Italy

[9] Kings Coll London, Guys Hosp, Acad Dept HIV & Genitourinary Med, London SE5 9RJ, England

[10] Kings Coll London, Kings Hosp, Acad Dept HIV & Genitourinary Med, London SE5 9RJ, England

[11] Kings Coll London, St Thomas Hosp, Acad Dept HIV & Genitourinary Med, London SE5 9RJ, England

[12] Univ Hosp Ctr, Infect Dis Serv, Dept Med, CH-1011 Lausanne, Switzerland

[13] Univ Hosp Ctr, Serv Hosp Prevent Med, CH-1011 Lausanne, Switzerland

[14] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia

[15] Murdoch Univ, Perth, WA 6000, Australia

[16] Irsicaixa Fdn, Badalona 08916, Spain

[17] Hosp Badalona Germans Trias & Pujol, Badalona 08916, Spain

[18] Inst Catalana Recerca & Estud Avancats, Barcelona, Spain

[19] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Spain

[20] Univ Copenhagen Hosp, Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark

[21] Univ Geneva, Natl Ctr Competence Res Frontiers Genet, CH-1211 Geneva, Switzerland

[22] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[23] Harvard Univ, Sch Med, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[24] John Radcliffe Hosp, Med Res Council Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England

[25] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA

来源：

SCIENCE | 2007年 / 317卷 / 5840期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1126/science.1143767

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：

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.

引用

页码：944 / 947

页数：4

共 23 条

[1] Nef interference with HIV-1-specific CTL antiviral activity is epitope specific [J].

Adnan, Sama ;

Balamurugan, Arumugam ;

Trocha, Alicja ;

Bennett, Michael S. ;

Ng, Hwee L. ;

Ali, Ayub ;

Brander, Christian ;

Yang, Otto O. .

BLOOD, 2006, 108 (10) :3414-3419

[2] Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection [J].

Altfeld, M ;

Addo, MA ;

Rosenberg, ES ;

Hecht, FA ;

Lee, PK ;

Vogel, M ;

Yu, XG ;

Draenert, R ;

Johnston, MN ;

Strick, D ;

Allen, TA ;

Feeney, ME ;

Kahn, JO ;

Sekaly, RP ;

Levy, JA ;

Rockstroh, JK ;

Goulder, PJR ;

Walker, BD .

AIDS, 2003, 17 (18) :2581-2591

[3] Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations [J].

Bailey, Justin R. ;

Williams, Thomas M. ;

Siliciano, Robert F. ;

Blankson, Joel N. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (05) :1357-1369

[4] Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression [J].

Bleiber, G ;

May, M ;

Martinez, R ;

Meylan, P ;

Ott, H ;

Beckmann, JS ;

Telenti, A .

JOURNAL OF VIROLOGY, 2005, 79 (20) :12674-12680

[5] The influence of HLA genotype on AIDS [J].

Carrington, M ;

O'Brien, SJ .

ANNUAL REVIEW OF MEDICINE, 2003, 54 :535-551

[6] Entry and transcription as key determinants of differences in CD4 T-cell permissiveness to human immunodeficiency virus type 1 infection [J].

Ciuffi, A ;

Bleiber, G ;

Muñoz, M ;

Martinez, R ;

Loeuillet, C ;

Rehr, M ;

Fischer, M ;

Günthard, HF ;

Oxenius, A ;

Meylan, P ;

Bonhoeffer, S ;

Trono, D ;

Telenti, A .

JOURNAL OF VIROLOGY, 2004, 78 (19) :10747-10754

[7] The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells [J].

Cohen, GB ;

Gandhi, RT ;

Davis, DM ;

Mandelboim, O ;

Chen, BK ;

Strominger, JL ;

Baltimore, D .

IMMUNITY, 1999, 10 (06) :661-671

[8] A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC [J].

de Bakker, Paul I. W. ;

McVean, Gil ;

Sabeti, Pardis C. ;

Miretti, Marcos M. ;

Green, Todd ;

Marchini, Jonathan ;

Ke, Xiayi ;

Monsuur, Alienke J. ;

Whittaker, Pamela ;

Delgado, Marcos ;

Morrison, Jonathan ;

Richardson, Angela ;

Walsh, Emily C. ;

Gao, Xiaojiang ;

Galver, Luana ;

Hart, John ;

Hafler, David A. ;

Pericak-Vance, Margaret ;

Todd, John A. ;

Daly, Mark J. ;

Trowsdale, John ;

Wijmenga, Cisca ;

Vyse, Tim J. ;

Beck, Stephan ;

Murray, Sarah Shaw ;

Carrington, Mary ;

Gregory, Simon ;

Deloukas, Panos ;

Rioux, John D. .

NATURE GENETICS, 2006, 38 (10) :1166-1172

[9] T cell dynamics in HIV-1 infection [J].

Douek, DC ;

Picker, LJ ;

Koup, RA .

ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :265-304

[10]

DUNDR M, 1995, J CELL SCI, V108, P2811

← 1 2 3 →