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Updated: Oct 6, 2025
Quantification of Filamentous Actin F-actin Puncta in Rat Cortical Neurons
Published on: February 10, 2016
Embedding of HIV Egress within Cortical F-Actin
Anupriya Aggarwal1, Alberto Ospina Stella1, Catherine C Henry2,3
1The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Insights
Human immunodeficiency virus (HIV) hijacks the actin cytoskeleton to spread via cell-cell contact. This study reveals how HIV corrupts actin dynamics, impacting viral release and infection.
Area of Science:
- Cell Biology
- Virology
- Biophysics
Background:
- Actin cytoskeleton remodeling is crucial for human immunodeficiency virus (HIV) cell-to-cell spread.
- The precise mechanisms by which HIV manipulates the actin cytoskeleton remain incompletely understood.
Purpose of the Study:
- To elucidate the role of F-Actin in HIV budding and cell-cell transmission.
- To identify the molecular pathways linking HIV egress, membrane curvature, and actin regulation.
Main Methods:
- Live cell imaging to observe dynamic F-Actin structures during HIV budding.
- Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) for high-resolution visualization of viral-actin interactions.
- Virion proteomics, gene silencing, and viral mutagenesis to identify key molecular players.
Main Results:
- HIV buds preferentially associate with positively curved F-Actin structures.
- A Cdc42-IQGAP1-Arp2/3 pathway is identified as a critical intersection for HIV budding, membrane curvature, and F-Actin regulation.
- While activating the Cdc42-Arp2/3 pathway promotes filopodial pathways, it impairs cell-free viral release, which can be restored by cell-cell contact.
Conclusions:
- HIV corrupts a central F-Actin node to couple viral buds to the actin cytoskeleton, positioning them at the cell edge.
- This initial coupling hinders particle release but is overcome upon maturation of cell-cell contacts, facilitating viral release and infection of the target cell.
Abstract:
F-Actin remodeling is important for the spread of HIV via cell-cell contacts; however, the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM), we observed F-Actin structures that exhibit strong positive curvature to be enriched for HIV buds. Virion proteomics, gene silencing, and viral mutagenesis supported a Cdc42-IQGAP1-Arp2/3 pathway as the primary intersection of HIV budding, membrane curvature and F-Actin regulation. Whilst HIV egress activated the Cdc42-Arp2/3 filopodial pathway, this came at the expense of cell-free viral release. Importantly, release could be rescued by cell-cell contact, provided Cdc42 and IQGAP1 were present. From these observations, we conclude that a proportion out-going HIV has corrupted a central F-Actin node that enables initial coupling of HIV buds to cortical F-Actin to place HIV at the leading cell edge. Whilst this initially prevents particle release, the maturation of cell-cell contacts signals back to this F-Actin node to enable viral release & subsequent infection of the contacting cell.
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