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Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53

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Inamdar, Kaushik | Tsai, Feng-Ching | Dibsy, Rayane | de Poret, Aurore | Manzi, John | Merida, Peggy | Muller, Remi | Lappalainen, Pekka | Roingeard, Philippe | Mak, Johnson | Bassereau, Patricia | Favard, Cyril | Muriaux, Delphine

Edité par CCSD ; eLife Sciences Publication -

International audience. 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.

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