A Genome-To-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Viral Control

Authors

• Istvan Bartha, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Eotvos Lorand University and the Hungarian Academy of Sciences - Budapest; Swiss Institute of Bioinformatics
• Jonathan M. Carlson, eScience Group
• Chanson J. Brumme, 6BC Centre for Excellence in HIV/AIDS - Vancouver, Canada
• Paul J. McLaren, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Swiss Institute of Bioinformatics
• Zabrina L. Brumme, BC Centre for Excellence in HIV/AIDS - Vancouver, Canada; Simon Fraser University - Canada
• Mina John, Murdoch University - Australia
• David W. Haas, Vanderbilt University
• Javier Martinez-Picado, Universitat Autònoma de Barcelona - Spain; Institució Catalana de Recerca i Estudis Avançats - Barcelona, Spain
• Judith Dalmau, Universitat Autònoma de Barcelona - Spain
• Cecilio Lopez-Galindez, Instituto de Salud Carlos III - Madrid, Spain
• Concepcion Casado, Instituto de Salud Carlos III - Madrid, Spain
• Andri Rauch, University of Bern & Inselspital - Switzerland
• Huldrych F. Gunthard, University of Zurich - Switzerland
• Enos Bernasconi, Regional Hospital of Lugano - Switzerland
• Pietro Vernazza, Cantonal Hospital - Switzerland
• Thomas Klimkait, University of Basel - Switzerland
• Sabine Yerly, Geneva University Hospitals - Switzerland
• Stephen J. O'Brien, St. Petersburg State University - RussiaFollow
• Jennifer Listgarten, eScience Group
• Nico Pfeifer, eScience Group
• Christoph Lippert, eScience Group
• Nicolo Fusi, eScience Group
• Zoltan Kutalik, Swiss Institute of Bioinformatics; University of Lausanne - Switzerland
• Todd M. Allen, Massachusetts General Hospital
• Viktor Muller, Eotvos Lorand University and the Hungarian Academy of Sciences - Budapest
• P. Richard Harrigan, BC Centre for Excellence in HIV/AIDS - Vancouver, Canada; University of British Columbia - Canada
• David Heckerman, eScience Group
• Amalio Telenti, University of Lausanne - Switzerland
• Jacques Fellay, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Swiss Institute of Bioinformatics

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

eLife

ISSN

2050-084X

Publication Date

10-29-2013

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.

Volume

2

Issue

e01123

First Page

1

Last Page

16

Comments

©Copyright Bartha et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Additional Comments

Swiss National Science Foundation grant #s: 33CS30_134277/Swiss HIV Cohort Study, 31003A_132863/1, PP00P3_133703/1; Sciex-NMS Program grant #: 10.267; Spanish Ministry of Science and Innovation grant #: SAF 2007-61036, 2010-17226, 2010-18917; Fundacion para la investigacion y prevencion del SIDA en Espana grant #s: 36558/06, 36641/07, 36779/08, 360766/09; RETIC de Investigacion en SIDA grant #: RD06/006/0036; National Institute of Allergy and Infectious Diseases grant #: P01-AI074415; SNF Professorship grant #: PP00P3_133703/1

NSUWorks Citation

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. https://nsuworks.nova.edu/cnso_bio_facarticles/751