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Elife. 2013 Oct 29;2:e01123. doi: 10.7554/eLife.01123.

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

Author information

1
School of Life Sciences , École Polytechnique Fédérale de Lausanne , Lausanne , Switzerland ; Institute of Microbiology , University Hospital and University of Lausanne , Lausanne , Switzerland ; Research Group of Theoretical Biology and Evolutionary Ecology , Eötvös Loránd University and the Hungarian Academy of Sciences , Budapest , Hungary ; Swiss Institute of Bioinformatics , Lausanne , Switzerland.

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. DOI:http://dx.doi.org/10.7554/eLife.01123.001.

KEYWORDS:

HIV; Human; human genomics; viral mutations

PMID:
24171102
PMCID:
PMC3807812
DOI:
10.7554/eLife.01123
[Indexed for MEDLINE]
Free PMC Article

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