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

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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