1. Physics of Living Systems
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Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53

  1. Kaushik Inamdar
  2. Feng-Ching Tsai
  3. Rayane Dibsy
  4. Aurore de Poret
  5. John Manzi
  6. Peggy Merida
  7. Remi Muller
  8. Pekka Lappalainen
  9. Philippe Roingeard
  10. Johnson Mak
  11. Patricia Bassereau
  12. Cyril Favard
  13. Delphine M Muriaux  Is a corresponding author
  1. CNRS, France
  2. Institut Curie, France
  3. University of Helsinki, Finland
  4. Faculté de Medecine, University of Tours, France
  5. Griffith University, Australia
  6. CNRS Délégation Languedoc Roussillon - Montpellier University, France
Research Article
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Cite this article as: eLife 2021;10:e67321 doi: 10.7554/eLife.67321

Abstract

During HIV-1 particle formation, the requisite plasma membrane curvature is thought to be solely driven by the retroviral Gag protein. Here, we reveal that the cellular I-BAR protein IRSp53 is required for the progression of HIV-1 membrane curvature to complete particle assembly. SiRNA-mediated knockdown of IRSp53 gene expression induces a decrease in viral particle production and a viral bud arrest at half completion. Single molecule localization microscopy at the cell plasma membrane shows a preferential localization of IRSp53 around HIV-1 Gag assembly sites. In addition, we observe the presence of IRSp53 in purified HIV-1 particles. Finally, HIV-1 Gag protein preferentially localizes to curved membranes induced by IRSp53 I-BAR domain on giant unilamellar vesicles. Overall, our data reveal a strong interplay between IRSp53 I-BAR and Gag at membranes during virus assembly. This highlights IRSp53 as a crucial host factor in HIV-1 membrane curvature and its requirement for full HIV-1 particle assembly.

Data availability

All data have been provided in the manuscript and supporting files in our submission that allows research reproductibility (see zipdataset, reagents table and supplemental informations).

Article and author information

Author details

  1. Kaushik Inamdar

    IRIM UMR9004, CNRS, Montpellier, France
    Competing interests
    No competing interests declared.
  2. Feng-Ching Tsai

    Laboratoire Physico Chimie Curie, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6869-5254
  3. Rayane Dibsy

    IRIM UMR9004, CNRS, Montpellier, France
    Competing interests
    No competing interests declared.
  4. Aurore de Poret

    IRIM UMR9004, CNRS, Montpellier, France
    Competing interests
    No competing interests declared.
  5. John Manzi

    Laboratoire Physico Chimie Curie, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
  6. Peggy Merida

    IRIM UMR9004, CNRS, Montpellier, France
    Competing interests
    No competing interests declared.
  7. Remi Muller

    CEMIPAI, CNRS, Montpellier, France
    Competing interests
    No competing interests declared.
  8. Pekka Lappalainen

    Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    Competing interests
    Pekka Lappalainen, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6227-0354
  9. Philippe Roingeard

    MAVIVH, Faculté de Medecine, University of Tours, Tours, France
    Competing interests
    No competing interests declared.
  10. Johnson Mak

    Griffith University, Brisbane, Australia
    Competing interests
    No competing interests declared.
  11. Patricia Bassereau

    Laboratoire Physico Chimie Curie, Institut Curie, Paris, France
    Competing interests
    Patricia Bassereau, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8544-6778
  12. Cyril Favard

    IRIM UMR9004, CNRS, Montpellier, France
    Competing interests
    No competing interests declared.
  13. Delphine M Muriaux

    Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS Délégation Languedoc Roussillon - Montpellier University, Montpellier, France
    For correspondence
    delphine.muriaux@irim.cnrs.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8517-9342

Funding

Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ECTZ35754)

  • Delphine M Muriaux

Agence Nationale de la Recherche (ANR10-INBS-04)

  • Patricia Bassereau

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

Reviewing Editor

  1. Felix Campelo, The Barcelona Institute of Science and Technology, Spain

Publication history

  1. Received: February 7, 2021
  2. Accepted: June 10, 2021
  3. Accepted Manuscript published: June 11, 2021 (version 1)

Copyright

© 2021, Inamdar 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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