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oai:repisalud.isciii.es:20.500.12105/76882024-09-27T20:49:46Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Bartha, István author Carlson, Jonathan M author Brumme, Chanson J author McLaren, Paul J author Brumme, Zabrina L author John, Mina author Haas, David W author Martinez-Picado, Javier author Dalmau, Judith author Lopez-Galindez, Luis Cecilio author Casado, Concepcion author Rauch, Andri author Günthard, Huldrych F author Bernasconi, Enos author Vernazza, Pietro author Klimkait, Thomas author Yerly, Sabine author O'Brien, Stephen J author Listgarten, Jennifer author Pfeifer, Nico author Lippert, Christoph author Fusi, Nicolo author Kutalik, Zoltán author Allen, Todd M author Müller, Viktor author Harrigan, P Richard author Heckerman, David author Telenti, Amalio author Fellay, Jacques author 2013-10-29 HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the 'intermediate phenotype' nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction. DOI:http://dx.doi.org/10.7554/eLife.01123.001. Elife. 2013 Oct 29;2:e01123. 10.7554/eLife.01123 2050-084X eLife 24171102 http://hdl.handle.net/20.500.12105/7688 HIV Human Human genomics Viral mutations A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control