DOI: 10.1126/science.1143767 ISSN:

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

Jacques Fellay, Kevin V. Shianna, Dongliang Ge, Sara Colombo, Bruno Ledergerber, Mike Weale, Kunlin Zhang, Curtis Gumbs, Antonella Castagna, Andrea Cossarizza, Alessandro Cozzi-Lepri, Andrea De Luca, Philippa Easterbrook, Patrick Francioli, Simon Mallal, Javier Martinez-Picado, José M. Miro, 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
  • Multidisciplinary

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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