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.
Bartha, Istvan; Jonathan M. Carlson; Chanson J. Brumme; Paul J. McLaren; Zabrina L. Brumme; Mina John; David W. Haas; Javier Martinez-Picado; Judith Dalmau; Cecilio Lopez-Galindez; Concepcion Casado; Andri Rauch; Huldrych F. Gunthard; Enos Bernasconi; Pietro Vernazza; Thomas Klimkait; Sabine Yerly; Stephen J. O'Brien; Jennifer Listgarten; Nico Pfeifer; Christoph Lippert; Nicolo Fusi; Zoltan Kutalik; Todd M. Allen; Viktor Muller; P. Richard Harrigan; David Heckerman; Amalio Telenti; and Jacques Fellay. 2013. "A Genome-To-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Viral Control." eLife 2, (e01123): 1-16. http://nsuworks.nova.edu/cnso_bio_facarticles/751