A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

Bartha, I.; Carlson, J. M.; Brumme, C. J.; McLaren, P. J.; Brumme, Z. L.; John, M.; Haas, D. W.; Martinez-Picado, J.; Dalmau, J.; Lopez-Galindez, C.; Casado, C.; Rauch, Andri; Gunthard, H. F.; Bernasconi, E.; Vernazza, P.; Klimkait, T.; Yerly, S.; O'Brien, S. J.; Listgarten, J.; Pfeifer, N.; ... (2013). A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife, 2(e01123) eLife Sciences Publications 10.7554/eLife.01123

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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.

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