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.
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).
- Delphine M Muriaux
- Patricia Bassereau
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Felix Campelo, The Barcelona Institute of Science and Technology, Spain
- Received: February 7, 2021
- Accepted: June 10, 2021
- Accepted Manuscript published: June 11, 2021 (version 1)
© 2021, Inamdar et al.
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