1. Genetics and Genomics
  2. Microbiology and Infectious Disease

Population genomics of intrapatient HIV-1 evolution

  1. Fabio Zanini
  2. Johanna Brodin
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Jan Albert
  7. Richard A Neher  Is a corresponding author
  1. Max Planck Institute for Developmental Biology, Germany
  2. Karolinska Institute, Sweden
  3. Stockholm South General Hospital, Sweden
  4. Karolinska Institutet, Sweden
https://doi.org/10.7554/eLife.11282
Share this article
Cite this article
  1. Fabio Zanini
  2. Johanna Brodin
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Jan Albert
  7. Richard A Neher
(2015)
Population genomics of intrapatient HIV-1 evolution
eLife 4:e11282.
https://doi.org/10.7554/eLife.11282
  2. Download BibTeX
  3. Download .RIS

Abstract

Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity.

Article and author information

Author details

  1. Fabio Zanini

    Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    No competing interests declared.

  2. Johanna Brodin

    Department of Microbiology Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    No competing interests declared.

  3. Lina Thebo

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    No competing interests declared.

  4. Christa Lanz

    Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    No competing interests declared.

  5. Göran Bratt

    Department of Clinical Science and Education, Stockholm South General Hospital, Stockholm, Sweden
    Competing interests
    No competing interests declared.

  6. Jan Albert

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.

  7. Richard A Neher

    Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany
    For correspondence
    richard.neher@tuebingen.mpg.de
    Competing interests
    Richard A Neher, Reviewing editor, eLife.

Ethics

Human subjects: The study was carried out according to the Declaration of Helsinki. Ethical approval was granted by the Regional Ethical Review board in Stockholm, Sweden (Dnr 2012/505-31/12). Patients participating in the study gave written and oral informed consent to participate.

Copyright

© 2015, Zanini et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 9,571
    views
  • 1,466
    downloads
  • 221
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Fabio Zanini
  2. Johanna Brodin
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Jan Albert
  7. Richard A Neher
(2015)
Population genomics of intrapatient HIV-1 evolution
eLife 4:e11282.
https://doi.org/10.7554/eLife.11282

Share this article

https://doi.org/10.7554/eLife.11282

Categories and tags

Research organism

Further reading

    1. Microbiology and Infectious Disease

    Establishment and stability of the latent HIV-1 DNA reservoir

    Johanna Brodin, Fabio Zanini ... Jan Albert
    Research Advance Updated

    HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini et al, 2015) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3–18 years of suppressive ART. A median of 14% (range 0–42%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.