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

Jitendriya Swain; Peggy Merida; Karla Rubio; David Bracquemond; Aymeric Neyret; Israel Aguilar-Ordoñez; Stefan Günther; Guillermo Barreto; Delphine Muriaux

doi:10.1016/j.isci.2023.107384

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

iScience. 2023 Jul 17;26(8):107384. doi: 10.1016/j.isci.2023.107384. eCollection 2023 Aug 18.

Authors

Jitendriya Swain¹, Peggy Merida¹, Karla Rubio^{2

3}, David Bracquemond¹, Aymeric Neyret⁴, Israel Aguilar-Ordoñez⁵, Stefan Günther⁶, Guillermo Barreto^{2

3}, Delphine Muriaux^{1

4}

Affiliations

¹ Institute of Research in Infectiology of Montpellier (IRIM), CNRS, University of Montpellier, UMR9004 CNRS, Montpellier, France.
² Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000 Nancy, France.
³ International Laboratory EPIGEN, Consejo de Ciencia y Tecnología del Estado de Puebla (CONCYTEP), Instituto de Ciencias, Ecocampus, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla 72570, Mexico.
⁴ CEMIPAI, CNRS, University of Montpellier, UAR3725 CNRS, Montpellier, France.
⁵ Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
⁶ ECCPS Bioinformatics and Deep Sequencing, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.

Abstract

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. Intracellular 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, filopodia-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 particles.

Keywords: Cell biology; Transcriptomics; Virology.