Embedding of HIV Egress within Cortical F-Actin
Anupriya Aggarwal; Alberto Ospina Stella; Catherine C. Henry; Kedar Narayan; Stuart G. Turville
F-Actin remodeling is important for the spread of HIV via cell&ndash: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&ndash: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&ndash:cell contacts signals back to this F-Actin node to enable viral release &: subsequent infection of the contacting cell.
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