New work published

Vasco's work on the front page of JCS

Gag paper Vasco Sarah
Maximum intensity projection image of a monocyte-derived macrophage at day 7 after infection with HIV-1 carrying GFP-tagged Gag (HIV-1-GAG-iGFP-ΔENV-VSVG, yellow). The cell is stained for F-actin (phalloidin-Alexa Fluor 647, magenta), and DNA is counterstained using DAPI (cyan), revealing a close association between F-actin and the HIV-1 virus-containing compartments. See article by V. Rodrigues et al. (jcs260511).


A feature of HIV-1 replication in macrophages is that viral assembly occurs at the limiting membrane of a compartment often named the virus-containing compartment (VCC). 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 performing experiments 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 (β2-integrin) and the phosphorylated form of PYK2 (also known as PTK2B) were displaced away from the VCC. Inhibition of PYK2 activity promoted retention of viral particles in VCCs that lost their connections to the surface. Finally, in infected macrophages undergoing frustrated phagocytosis, VCCs 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 the trafficking of VCCs and virus release are intimately linked to a reorganization of the macrophage actin cytoskeleton that can be modulated by external physical cues.