F-actin nanostructures rearrangements and regulation are essential for SARS-CoV-2 particle production in host pulmonary cells

Our study focused on deciphering the role of F-actin and related regulatory factors during SARS-CoV-2 particle production and transmission in human pulmonary cells. Quantitative high-resolution microscopies revealed that the late phases of SARS-CoV-2 infection induce a strong rearrangement of F-actin nanostructures dependent on the viral M, E, and N structural proteins. Intracel-lular vesicles containing viral components are labeled with Rab7 and Lamp1 and are surrounded by F-actin ring-shaped structures, suggesting their role in viral trafficking toward the cell membrane for virus release. Furthermore, filopo-dia-like nanostructures were loaded with viruses, potentially facilitating their egress and transmission between lung cells. Gene expression analysis revealed the involvement of alpha-actinins under the regulation of the protein kinase N (PKN). The use of a PKN inhibitor efficiently reduces virus particle production, restoring endoplasmic reticulum and F-actin cellular shape. Our results highlight an important role of F-actin rearrangements during the productive phases of SARS-CoV-2

Automated summary

Our study focused on the role of F-actin and related regulatory factors in the production and transmission of SARS-CoV-2 particles in human pulmonary cells. High-resolution microscopies revealed that F-actin rearrangements play a crucial role in viral trafficking and release. Filopodia-like nanostructures loaded with viruses may facilitate virus egress and transmission between lung cells.