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

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

Version history

  1. Received: February 7, 2021
  2. Accepted: June 10, 2021
  3. Accepted Manuscript published: June 11, 2021 (version 1)
  4. Version of Record published: July 6, 2021 (version 2)

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.

Metrics

  • 1,797
    views
  • 321
    downloads
  • 25
    citations

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

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. 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
(2021)
Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53
eLife 10:e67321.
https://doi.org/10.7554/eLife.67321

Share this article

https://doi.org/10.7554/eLife.67321

Further reading

    1. Developmental Biology
    2. Physics of Living Systems
    Raphaël Clément
    Insight

    Geometric criteria can be used to assess whether cell intercalation is active or passive during the convergent extension of tissue.

    1. Computational and Systems Biology
    2. Physics of Living Systems
    Taegon Chung, Iksoo Chang, Sangyeol Kim
    Research Article

    Locomotion is a fundamental behavior of Caenorhabditis elegans (C. elegans). Previous works on kinetic simulations of animals helped researchers understand the physical mechanisms of locomotion and the muscle-controlling principles of neuronal circuits as an actuator part. It has yet to be understood how C. elegans utilizes the frictional forces caused by the tension of its muscles to perform sequenced locomotive behaviors. Here, we present a two-dimensional rigid body chain model for the locomotion of C. elegans by developing Newtonian equations of motion for each body segment of C. elegans. Having accounted for friction-coefficients of the surrounding environment, elastic constants of C. elegans, and its kymogram from experiments, our kinetic model (ElegansBot) reproduced various locomotion of C. elegans such as, but not limited to, forward-backward-(omega turn)-forward locomotion constituting escaping behavior and delta-turn navigation. Additionally, ElegansBot precisely quantified the forces acting on each body segment of C. elegans to allow investigation of the force distribution. This model will facilitate our understanding of the detailed mechanism of various locomotive behaviors at any given friction-coefficients of the surrounding environment. Furthermore, as the model ensures the performance of realistic behavior, it can be used to research actuator-controller interaction between muscles and neuronal circuits.