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

55 Pages Posted: 6 Dec 2022 Publication Status: Published

See all articles by Jitendriya Swain

Jitendriya Swain

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM)

Peggy Merida

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM)

Karla Rubio

University of Lorraine - Laboratoire Ingénierie Moléculaire et Physiopathologie Articulaire - IMoPA; Max Planck Institute for Heart and Lung Research

David Bracquemond

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM)

Aymeric Neyret

University of Montpellier - Centre d’Etudes des Maladies Infectieuses et Pharmacologie Anti-Infectieuse (CEMIPAI) - CNRS UAR3725

Israel Aguilar-Ordoñez

Instituto Nacional de Medicina Genómica

Stephan Guenther

Max Planck Institute for Heart and Lung Research - ECCPS Bioinformatics and Deep Sequencing

Guillermo Barreto

University of Lorraine - Laboratoire Ingénierie Moléculaire et Physiopathologie Articulaire - IMoPA

Delphine Muriaux

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM)

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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

Suggested Citation

Swain, Jitendriya and Merida, Peggy and Rubio, Karla and Bracquemond, David and Neyret, Aymeric and Aguilar-Ordoñez, Israel and Guenther, Stephan and Barreto, Guillermo and Muriaux, Delphine, F-Actin Nanostructures Rearrangements and Regulation Are Essential for SARS-CoV2 Particle Production in Host Pulmonary Cells. Available at SSRN: https://ssrn.com/abstract=4290055 or http://dx.doi.org/10.2139/ssrn.4290055
This version of the paper has not been formally peer reviewed.

Jitendriya Swain

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM) ( email )

Peggy Merida

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM) ( email )

Karla Rubio

University of Lorraine - Laboratoire Ingénierie Moléculaire et Physiopathologie Articulaire - IMoPA ( email )

Max Planck Institute for Heart and Lung Research ( email )

Parkstrasse 1
61231 Bad Nauheim
Germany

David Bracquemond

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM) ( email )

Aymeric Neyret

University of Montpellier - Centre d’Etudes des Maladies Infectieuses et Pharmacologie Anti-Infectieuse (CEMIPAI) - CNRS UAR3725 ( email )

Israel Aguilar-Ordoñez

Instituto Nacional de Medicina Genómica ( email )

Stephan Guenther

Max Planck Institute for Heart and Lung Research - ECCPS Bioinformatics and Deep Sequencing ( email )

Guillermo Barreto

University of Lorraine - Laboratoire Ingénierie Moléculaire et Physiopathologie Articulaire - IMoPA ( email )

Delphine Muriaux (Contact Author)

University of Montpellier - Institut de Recherche en Infectiologie de Montpellier (IRIM) ( email )

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