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
Affiliations
Jitendriya Swain
Institute of Research in Infectiology of Montpellier (IRIM), CNRS, University of Montpellier, UMR9004 CNRS, Montpellier, France
Peggy Merida
Institute of Research in Infectiology of Montpellier (IRIM), CNRS, University of Montpellier, UMR9004 CNRS, Montpellier, France
Karla Rubio
Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000 Nancy, France; 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
David Bracquemond
Institute of Research in Infectiology of Montpellier (IRIM), CNRS, University of Montpellier, UMR9004 CNRS, Montpellier, France
Aymeric Neyret
CEMIPAI, CNRS, University of Montpellier, UAR3725 CNRS, Montpellier, France
Israel Aguilar-Ordoñez
Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Stefan Günther
ECCPS Bioinformatics and Deep Sequencing, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
Guillermo Barreto
Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000 Nancy, France; 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
Delphine Muriaux
Institute of Research in Infectiology of Montpellier (IRIM), CNRS, University of Montpellier, UMR9004 CNRS, Montpellier, France; CEMIPAI, CNRS, University of Montpellier, UAR3725 CNRS, Montpellier, France; Corresponding author
Summary: 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.
