Establishment and stability of the latent HIV-1 DNA reservoir

  1. Johanna Brodin
  2. Fabio Zanini
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Richard A Neher
  7. Jan Albert  Is a corresponding author
  1. Karolinska Institute, Sweden
  2. Stanford University, United States
  3. Max Planck Institute for Developmental Biology, Germany
  4. Stockholm South General Hospital, Sweden

Abstract

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, 2015) we documented HIV-1 evolution 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.

Data availability

The following data sets were generated
The following previously published data sets were used
    1. Zanini F
    2. Neher R
    (2015) HIVEVO
    Publicly available at the EBI European Nucleotide Archive (Accession no: PRJEB9618).

Article and author information

Author details

  1. Johanna Brodin

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

    Stanford University, Stanford, United States
    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

    Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    No competing interests declared.
  5. Göran Bratt

    Department of Clinical Science and Education, Venhälsan, Stockholm South General Hospital, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  6. Richard A Neher

    Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    Richard A Neher, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2525-1407
  7. Jan Albert

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
    For correspondence
    Jan.Albert@ki.se
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9020-0521

Funding

European Research Council (Stg. 260686)

  • Richard A Neher

Vetenskapsrådet (K2014-57X-09935)

  • Jan Albert

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was conducted according to the Declaration of Helsinki. Ethical approval was granted by the Regional Ethical Review board in Stockholm, Sweden (Dnr 2012/505 and 2014/646). Patients participating in the study gave written and oral informed consent to participate.

Reviewing Editor

  1. Arup K Chakraborty, Massachusetts Institute of Technology, United States

Publication history

  1. Received: June 20, 2016
  2. Accepted: November 1, 2016
  3. Accepted Manuscript published: November 15, 2016 (version 1)
  4. Version of Record published: December 30, 2016 (version 2)

Copyright

© 2016, Brodin 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.

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  1. Johanna Brodin
  2. Fabio Zanini
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Richard A Neher
  7. Jan Albert
(2016)
Establishment and stability of the latent HIV-1 DNA reservoir
eLife 5:e18889.
https://doi.org/10.7554/eLife.18889
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