Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53
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
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
- Felix Campelo, The Barcelona Institute of Science and Technology, Spain
Version history
- Received: February 7, 2021
- Accepted: June 10, 2021
- Accepted Manuscript published: June 11, 2021 (version 1)
- 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.
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