1. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
- Author
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Istvan Bartha, Paul J. McLaren, Nico Pfeifer, David W. Haas, Stephen J. O'Brien, Jonathan M. Carlson, Jennifer Listgarten, Todd M. Allen, Huldrych F. Günthard, Zabrina L. Brumme, Thomas Klimkait, Pietro Vernazza, Zoltán Kutalik, Judith Dalmau, P. Richard Harrigan, Amalio Telenti, Chanson J. Brumme, Nicolo Fusi, Enos Bernasconi, David Heckerman, Javier Martinez-Picado, Mina John, Jacques Fellay, Cecilio López-Galíndez, Concepción Casado, Sabine Yerly, Andri Rauch, Viktor Müller, Christoph Lippert, Swiss National Science Foundation, Fundación para la Investigación y la Prevención del Sida en España, Ministerio de Ciencia e Innovación (España), University of Zurich, and Telenti, Amalio
- Subjects
Human genomics ,Genome-wide association study ,HIV Infections ,Human genetic variation ,Genome ,10234 Clinic for Infectious Diseases ,0302 clinical medicine ,2400 General Immunology and Microbiology ,Biology (General) ,ddc:616 ,Genetics ,0303 health sciences ,Microbiology and Infectious Disease ,General Neuroscience ,2800 General Neuroscience ,General Medicine ,Viral Load ,3. Good health ,human genomics ,Genomics and Evolutionary Biology ,Host-Pathogen Interactions ,Medicine ,Viral load ,Research Article ,Human ,QH301-705.5 ,Science ,Single-nucleotide polymorphism ,610 Medicine & health ,Genome, Viral ,Biology ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,1300 General Biochemistry, Genetics and Molecular Biology ,SNP ,Humans ,Allele ,Alleles ,030304 developmental biology ,Viral mutations ,General Immunology and Microbiology ,Genome, Human ,Histocompatibility Antigens Class I ,HIV ,Cardiovascular and Metabolic Diseases ,HIV-1 ,viral mutation ,Human genome ,viral mutations ,030217 neurology & neurosurgery ,Genome-Wide Association Study - 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, eLife digest Developing treatments or vaccines for HIV is challenging because the genetic makeup of the virus is constantly changing in an effort to outwit the human immune system. Moreover, the immune system is highly variable as a result of the long-standing co-evolution of humans and microbes. Each individual will try to oppose the invading virus in a unique way, forcing the virus to acquire specific mutations that can be interpreted as the genetic signature of this one-against-one battle. To explore the influence of co-evolution on HIV, Bartha et al. took samples of both human and viral genomes from 1071 individuals infected with HIV, the AIDS virus, and used genotyping and sequencing technology to obtain a comprehensive description of the genetic variation in both. Computational techniques were then used to search for links between variants in the human DNA sequences and variants in the viral sequences. The most common type of genetic variation found in the human genome is a single nucleotide polymorphism, or SNP for short: a SNP is produced when a single nucleotide – an A, C, G or T – is replaced by a different nucleotide. Bartha et al. found that SNPs within the human DNA sequences in their study were linked to variations in 48 amino acids in HIV. Moreover, all these SNPs were found within a group of genes known as the HLA (human leukocyte antigen) system, which encodes for proteins that play a vital role in the immune response. This work identified the areas of the human genome that put pressure on the AIDS virus, and the regions of the virus that serve to escape human control. The approach developed by Bartha et al. allows the interactions between a microbe and a human host to be studied by looking at the genome of the microbe and the genome of the infected person. It also differentiates host-induced mutations that limit the capacity of the virus to do harm from those that are tolerated by the pathogen. A similar strategy could be used to study other infectious diseases. DOI: http://dx.doi.org/10.7554/eLife.01123.002
- Published
- 2013