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Originally published in Science Express on 19 July 2007
Science 17 August 2007:
Vol. 317. no. 5840, pp. 944 - 947
DOI: 10.1126/science.1143767
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Reports

A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1

Jacques Fellay,1 Kevin V. Shianna,2* Dongliang Ge,1* Sara Colombo,3* Bruno Ledergerber,4* Mike Weale,1* Kunlin Zhang,3 Curtis Gumbs,1 Antonella Castagna,5 Andrea Cossarizza,6 Alessandro Cozzi-Lepri,7 Andrea De Luca,8 Philippa Easterbrook,9 Patrick Francioli,10 Simon Mallal,11 Javier Martinez-Picado,12 José M. Miro,13 Niels Obel,14 Jason P. Smith,2 Josiane Wyniger,3 Patrick Descombes,15 Stylianos E. Antonarakis,16 Norman L. Letvin,17 Andrew J. McMichael,18 Barton F. Haynes,19 Amalio Telenti,3{dagger} David B. Goldstein1{dagger}{ddagger}

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.

1 Center for Population Genomics and Pharmacogenetics, Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
2 Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
3 Institute of Microbiology, University Hospital Center; and University of Lausanne, 1011 Lausanne, Switzerland.
4 Division of Infectious Diseases, University Hospital, 8091 Zürich, Switzerland.
5 Clinic of Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Hospital, 20127 Milan, Italy.
6 Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia, School of Medicine, 41100 Modena, Italy.
7 Department of Primary Care and Population Sciences, Royal Free and University College Medical School, University College London, London NW3 2PF, UK.
8 Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, 00168 Rome, Italy.
9 Academic Department of HIV and Genitourinary Medicine, Kings College London, at Guy's, King's, and St. Thomas' Hospitals, London SE5 9RJ, UK.
10 Service of Infectious Diseases, Department of Medicine and Service of Hospital Preventive Medicine, University Hospital Center, 1011 Lausanne, Switzerland.
11 Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital; and Murdoch University, Perth, WA 6000, Australia.
12 irsiCaixa Foundation and Hospital Germans Trias i Pujol, 08916 Badalona, Spain; and Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
13 Hospital Clinic–Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, 08036 Barcelona, Spain.
14 Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.
15 Genomics Platform, National Centre of Competence in Research "Frontiers in Genetics," University of Geneva, 1211 Geneva, Switzerland.
16 Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
17 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
18 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
19 Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.

* These authors contributed equally to this work.

{ddagger} On behalf of the Center for HIV/AIDS Vaccine Immunology (CHAVI) and the Euro-CHAVI consortia.

{dagger} To whom correspondence should be addressed. E-mail: amalio.telenti{at}chuv.ch (A.T.); d.goldstein{at}duke.edu (D.B.G.)

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J. R. Bailey, K. O'Connell, H.-C. Yang, Y. Han, J. Xu, B. Jilek, T. M. Williams, S. C. Ray, R. F. Siliciano, and J. N. Blankson (2008)
J. Virol. 82, 7395-7410
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HLA Class I-Driven Evolution of Human Immunodeficiency Virus Type 1 Subtype C Proteome: Immune Escape and Viral Load.
C. M. Rousseau, M. G. Daniels, J. M. Carlson, C. Kadie, H. Crawford, A. Prendergast, P. Matthews, R. Payne, M. Rolland, D. N. Raugi, et al. (2008)
J. Virol. 82, 6434-6446
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Microarray Technology and Applications in the Arena of Genome-Wide Association.
S. F. A. Grant and H. Hakonarson (2008)
Clin. Chem. 54, 1116-1124
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HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control.
B. Emu, E. Sinclair, H. Hatano, A. Ferre, B. Shacklett, J. N. Martin, J. M. McCune, and S. G. Deeks (2008)
J. Virol. 82, 5398-5407
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WGAViewer: Software for genomic annotation of whole genome association studies.
D. Ge, K. Zhang, A. C. Need, O. Martin, J. Fellay, T. J. Urban, A. Telenti, and D. B. Goldstein (2008)
Genome Res. 18, 640-643
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Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen.
A. L. Brass, D. M. Dykxhoorn, Y. Benita, N. Yan, A. Engelman, R. J. Xavier, J. Lieberman, and S. J. Elledge (2008)
Science 319, 921-926
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Whole-Genome Study Reveals Clues for Improving Host Control of HIV.
(2007)
Journal Watch (General) 2007, 9
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SNPing HIV Viral Load.
(2007)
Journal Watch Infectious Diseases 2007, 3
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Science. ISSN 0036-8075 (print), 1095-9203 (online)