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Title

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

Authors
Bartha, István
Carlson, Jonathan M
Brumme, Chanson J
McLaren, Paul J
Brumme, Zabrina L
John, Mina
Haas, David W
Martinez-Picado, Javier
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Published in eLife. 2013, vol. 2, p. e01123
Abstract 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.
Identifiers
PMID: 24171102
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Research group Groupe Laurent Kaiser (virologie clinique) (668)
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BARTHA, István et al. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. In: eLife, 2013, vol. 2, p. e01123. https://archive-ouverte.unige.ch/unige:40770

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Deposited on : 2014-10-09

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