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

Elife. 2021 Jun 11:10:e67321. doi: 10.7554/eLife.67321.

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.

Keywords: physics of living systems; plasma membrane; single molecule localisation microscopy; virus; viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism
  • HEK293 Cells
  • HIV-1 / metabolism*
  • HIV-1 / physiology
  • Humans
  • Jurkat Cells
  • Nerve Tissue Proteins / metabolism*
  • Single Molecule Imaging / methods
  • Virion / metabolism*
  • Virus Assembly*
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • BAIAP2 protein, human
  • Nerve Tissue Proteins
  • gag Gene Products, Human Immunodeficiency Virus

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.