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