F-Actin Nanostructures Rearrangements and Regulation Are Essential for SARS-CoV2 Particle Production in Host Pulmonary Cells

Abstract

The coronavirus SARS-CoV-2 is the main cause of a recent mortal ongoing pandemic. Important details on the role of actin cytoskeleton and related host factors during the late phases of infection in host cells are missing. Here, we focused on deciphering the role of F-actin and related regulatory factors during SARS-CoV-2 particle production and transmission in lung cancer cells.  Quantitative high-resolution microscopies revealed that the late phases of SARS-CoV-2 infection induces a strong rearrangement of F-actin nanostructures. Virus-containing vesicles carrying Rab7 and Lamp1 are surrounded by F-actin ring-shaped structures, most probably responsible for viruses trafficking towards the cell plasma membrane for egress. Furthermore filopodia-like nanostructures were loaded with viruses suggested a way for viral particles transmission between lung cancer cells. Gene expression profiles also reveal the involvement of the host factor alpha-actinins under the regulation of Protein Kinase N (PKN). Thus, the use of PKN inhibitor efficiently reduces virus particle production, restoring F-actin cell shape. Our results highlight important F-actin rearrangements during the productive phases of SARS-CoV-2 particles.

Note:

Funding Information: Delphine Muriaux was funded by the “Centre National de la Recherche Scientifique” (CNRS, France), Montpellier University through a Montpellier University of Excellence (MUSE) support and by the French Agency for Research (ANR COVID19) grant “NucleoCoV-2”. J.Swain was funded by the Mediterranee foundation, Marseille, France. Guillermo Barreto was funded by the “Centre National de la Recherche Scientifique” (CNRS, France), “Délégation Centre-Est” (CNRS-DR6), the “Lorraine Université” (LU, France) through the initiative “Lorraine Université d’Excellence” (LUE) and the dispositive “Future Leader” and the “Deutsche Forschungsgemeinschaft” (DFG, Bonn, Germany) (BA 4036/4-1). Karla Rubio was funded by the “Consejo de Ciencia y Tecnología del Estado de Puebla” (CONCYTEP, Puebla, Mexico) through the initiative International Laboratory EPIGEN.

Declaration of Interests: All other authors declare they have no competing interests.

Keywords: SARS-CoV-2 - actin cytoskeleton - STED microscopy - pulmonary cells - RNAseq