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

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

eLife digest

Affiliation details

École Polytechnique Fédérale de Lausanne, Switzerland; University Hospital and University of Lausanne, Switzerland; Eötvös Loránd University and the Hungarian Academy of Sciences, Hungary; Swiss Institute of Bioinformatics, Switzerland; Microsoft Research, United States; BC Centre for Excellence in HIV/AIDS, Canada; Simon Fraser University, Canada; Murdoch University, Australia; Vanderbilt University Medical Center, United States; Universitat Autònoma de Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Spain; Instituto de Salud Carlos III, Spain; University of Bern & Inselspital, Switzerland; University Hospital and University of Zürich, Switzerland; Regional Hospital of Lugano, Switzerland; Cantonal Hospital, Switzerland; University of Basel, Switzerland; Geneva University Hospitals, Switzerland; St. Petersburg State University, Russia; Massachusetts General Hospital, United States; University of British Columbia, Canada

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