Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53.
Kaushik InamdarFeng-Ching TsaiRayane DibsyAurore de PoretJohn ManziPeggy MeridaRemi MullerPekka LappalainenPhilippe RoingeardJohnson MakPatricia BassereauCyril FavardDelphine MuriauxPublished in: eLife (2021)
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.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv testing
- hiv infected
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- gene expression
- south africa
- dna methylation
- drug delivery
- stem cells
- high resolution
- single cell
- mass spectrometry
- big data
- small molecule
- binding protein
- artificial intelligence
- electronic health record
- amino acid
- protein protein
- label free