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

2007; American Association for the Advancement of Science; Volume: 317; Issue: 5840 Linguagem: Inglês

10.1126/science.1143767

1095-9203

Jacques Fellay, Kevin V. Shianna, Dongliang Ge, Sara Colombo, Bruno Ledergerber, Michael E. Weale, Kunlin Zhang, Curtis Gumbs, Antonella Castagna, Andrea Cossarizza, Alessandro Cozzi‐Lepri, Andrea De Luca, Philippa Easterbrook, P Francioli, S. Mallal, Javier Martínez‐Picado, José M. Miró, Niels Obel, Jason P. Smith, Josiane Wyniger, Patrick Descombes, Stylianos E. Antonarakis, Norman L. Letvin, Andrew J. McMichael, Barton F. Haynes, Amalio Telenti, David B. Goldstein,

Genetic Associations and Epidemiology

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.