Abstract

Numerous challenges have impeded HIV-1 vaccine development. Among these is the lack of a convenient small animal model in which to study antibody elicitation and efficacy. We describe a chimeric Rhabdo-Immunodeficiency virus (RhIV) murine model that recapitulates key features of HIV-1 entry, tropism and antibody sensitivity. RhIVs are based on vesicular stomatitis viruses (VSV), but viral entry is mediated by HIV-1 Env proteins from diverse HIV-1 strains. RhIV infection of transgenic mice expressing human CD4 and CCR5, exclusively on mouse CD4+ cells, at levels mimicking those on human CD4+ T-cells, resulted in acute, resolving viremia and CD4+ T-cell depletion. RhIV infection elicited protective immunity, and antibodies to HIV-1 Env that were primarily non-neutralizing and had modest protective efficacy following passive transfer. The RhIV model enables the convenient in vivo study of HIV-1 Env-receptor interactions, antiviral activity of antibodies and humoral responses against HIV-1 Env, in a genetically manipulatable host.

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All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Rachel A Liberatore

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Emily J Mastrocola

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Elena Cassella

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fabian Schmidt

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jesse R Willen

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Denis Voronin

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Trinity M Zang

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Theodora Hatziioannou

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Paul D Bieniasz

    Laboratory of Retrovirology, The Rockefeller University, New York, United States
    For correspondence
    pbieniasz@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2368-3719

Funding

National Institute of Allergy and Infectious Diseases (R37AI064003)

  • Paul D Bieniasz

National Institute of Allergy and Infectious Diseases (R01AI078788)

  • Theodora Hatziioannou

National Institute of Allergy and Infectious Diseases (R01AI50111)

  • Paul D Bieniasz

Howard Hughes Medical Institute

  • Paul D Bieniasz

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

Reviewing Editor

  1. Frank Kirchhoff, Ulm University Medical Center, Germany

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (18047-H) of the Rockefeller University. All surgery was performed under anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: July 3, 2019
  2. Accepted: October 22, 2019
  3. Accepted Manuscript published: October 23, 2019 (version 1)
  4. Accepted Manuscript updated: October 24, 2019 (version 2)
  5. Version of Record published: November 22, 2019 (version 3)

Copyright

© 2019, Liberatore 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. Rachel A Liberatore
  2. Emily J Mastrocola
  3. Elena Cassella
  4. Fabian Schmidt
  5. Jesse R Willen
  6. Denis Voronin
  7. Trinity M Zang
  8. Theodora Hatziioannou
  9. Paul D Bieniasz
(2019)
Rhabdo-immunodeficiency virus, a murine model of acute HIV-1 infection
eLife 8:e49875.
https://doi.org/10.7554/eLife.49875

Share this article

https://doi.org/10.7554/eLife.49875

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