LAUSR

A feature of HIV-1 replication in macrophages is that viral assembly occurs at the limiting membrane of a compartment often named VCC (virus-containing compartments). Assembled virions accumulate in the lumen of the VCC, from where they can be released into the extracellular medium, via mechanisms that remain poorly described. Here we show that the actin cytoskeleton contributes to this process by combining pharmacological and mechanical perturbations with imaging and biochemical analysis. We found that jasplakinolide inhibited HIV-1 release from macrophages and led to scattering of the compartment. Concomitantly, both the integrin CD18 and the phosphorylated form of PYK2 were displaced away from the VCC. Inhibition of PYK2 activity promoted retention of viral particles in VCC that lost their connections to the surface. Finally, in infected macrophages undergoing frustrated phagocytosis, VCC rapidly trafficked to the basal membrane and released their viral content, in a manner dependent on their association with the actin cytoskeleton. These results highlight that VCC trafficking and virus release are intimately linked to the reorganization of the macrophage actin cytoskeleton that can be modulated by external physical cues.