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 M
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2021
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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.

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Elife

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10

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© 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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Biochemistry and cell biology

physics of living systems

viruses

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Inamdar, K; Tsai, F-C; Dibsy, R; de Poret, A; Manzi, J; Merida, P; Muller, R; Lappalainen, P; Roingeard, P; Mak, J; Bassereau, P; Favard, C; Muriaux, DM, Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53, Elife, 2021, 10, pp. e67321

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