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

Kaushik Inamdar (1) , Feng-Ching Tsai (2) , Rayane Dibsy (1) , Aurore de Poret (1) , John Manzi (2) , Peggy Merida (1) , Remi Muller (3) , Pekka Lappalainen (4) , Philippe Roingeard (5) , Johnson Mak (6) , Patricia Bassereau (2) , Cyril Favard (1) , Delphine Muriaux (1)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 PCC - Laboratoire Physico-Chimie Curie [Institut Curie]
3 CEMIPAI - Centre d’études des Maladies Infectieuses et Pharmacologie Anti-Infectieuse - [Montpellier]
4 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
5 MAVIVHe - Morphogénèse et antigénicité du VIH, des Virus des Hépatites et Emergents
6 Griffith University [Brisbane]

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.

Domaines: Matière Molle [cond-mat.soft]; Organisation et fonctions cellulaires [q-bio.SC]; Biophysique

Kaushik Inamdar, Feng-Ching Tsai, Rayane Dibsy, Aurore de Poret, John Manzi, et al.. Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53. eLife, 2021, 10, ⟨10.7554/elife.67321⟩. ⟨hal-03366982⟩