eLife (Oct 2013)
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
- István Bartha,
- Jonathan M Carlson,
- Chanson J Brumme,
- Paul J McLaren,
- Zabrina L Brumme,
- Mina John,
- David W Haas,
- Javier Martinez-Picado,
- Judith Dalmau,
- Cecilio López-Galíndez,
- Concepción Casado,
- Andri Rauch,
- Huldrych F Günthard,
- Enos Bernasconi,
- Pietro Vernazza,
- Thomas Klimkait,
- Sabine Yerly,
- Stephen J O’Brien,
- Jennifer Listgarten,
- Nico Pfeifer,
- Christoph Lippert,
- Nicolo Fusi,
- Zoltán Kutalik,
- Todd M Allen,
- Viktor Müller,
- P Richard Harrigan,
- David Heckerman,
- Amalio Telenti,
- Jacques Fellay,
- for the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study
Affiliations
- István Bartha
- 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
- Jonathan M Carlson
- eScience Group, Microsoft Research, Los Angeles, United States
- Chanson J Brumme
- BC Centre for Excellence in HIV/AIDS, Vancouver, Canada
- Paul J McLaren
- School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland
- Zabrina L Brumme
- BC Centre for Excellence in HIV/AIDS, Vancouver, Canada; Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada
- Mina John
- Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia
- David W Haas
- Vanderbilt University Medical Center, Nashville, United States
- Javier Martinez-Picado
- AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
- Judith Dalmau
- AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
- Cecilio López-Galíndez
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
- Concepción Casado
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
- Andri Rauch
- Clinic of Infectious Diseases, University of Bern & Inselspital, Bern, Switzerland
- Huldrych F Günthard
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zürich, Zürich, Switzerland
- Enos Bernasconi
- Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland
- Pietro Vernazza
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital, St. Gallen, Switzerland
- Thomas Klimkait
- Department of Biomedicine, University of Basel, Basel, Switzerland
- Sabine Yerly
- Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland
- Stephen J O’Brien
- Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia
- Jennifer Listgarten
- eScience Group, Microsoft Research, Los Angeles, United States
- Nico Pfeifer
- eScience Group, Microsoft Research, Los Angeles, United States
- Christoph Lippert
- eScience Group, Microsoft Research, Los Angeles, United States
- Nicolo Fusi
- eScience Group, Microsoft Research, Los Angeles, United States
- Zoltán Kutalik
- Swiss Institute of Bioinformatics, Lausanne, Switzerland; Institute of Social and Preventive Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland
- Todd M Allen
- Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Boston, United States
- Viktor Müller
- Research Group of Theoretical Biology and Evolutionary Ecology, Eötvös Loránd University and the Hungarian Academy of Sciences, Budapest, Hungary
- P Richard Harrigan
- BC Centre for Excellence in HIV/AIDS, Vancouver, Canada; Faculty of Medicine, University of British Columbia, Vancouver, Canada
- David Heckerman
- eScience Group, Microsoft Research, Los Angeles, United States
- Amalio Telenti
- Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland
- Jacques Fellay
- School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland
- for the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study
- DOI
- https://doi.org/10.7554/eLife.01123
- Journal volume & issue
-
Vol. 2
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.
Keywords
