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

Jacques Fellay(Duke University), Kevin V. Shianna(Duke University), Dongliang Ge(Duke University), Sara Colombo(Duke University), Bruno Ledergerber(Duke University), Mike Weale(Duke University), Kunlin Zhang(Duke University), Curtis Gumbs(Duke University), Antonella Castagna(Duke University), Andrea Cossarizza(University of Modena and Reggio Emilia), Alessandro Cozzi‐Lepri(Duke University), Andrea De Luca(Duke University), Philippa Easterbrook(St Thomas' Hospital), P Francioli(Duke University), S. Mallal(Duke University), Javier Martínez‐Picado(Duke University), José M. Miró(Duke University), Niels Obel(Duke University), Jason P. Smith(Duke University), Josiane Wyniger(Duke University), Patrick Descombes(Duke University), Stylianos E. Antonarakis(Duke University), Norman L. Letvin(Duke University), Andrew J. McMichael(Duke University), Barton F. Haynes(Duke University), Amalio Telenti(Duke University), David B. Goldstein(Duke University)
Science
July 20, 2007
Cited by 1,237Open Access
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Abstract

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.


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