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Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection

Small Extracellular Vesicles (sEVs) are 50–200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role...

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Autores principales: Berry, François, Morin‐Dewaele, Margot, Majidipur, Amene, Jamet, Thibaud, Bartier, Sophie, Ignjatovic, Eva, Toniutti, Donatella, Gaspar Lopes, Jeanne, Soyeux‐Porte, Pascale, Maillé, Pascale, Saldana, Carolina, Brillet, Rozenn, Ahnou, Nazim, Softic, Laurent, Couturaud, Benoit, Huet, Éric, Ahmed‐Belkacem, Abdelhakim, Fourati, Slim, Louis, Bruno, Coste, André, Béquignon, Émilie, de la Taille, Alexandre, Destouches, Damien, Vacherot, Francis, Pawlotsky, Jean‐Michel, Firlej, Virginie, Bruscella, Patrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587708/
https://www.ncbi.nlm.nih.gov/pubmed/36271885
http://dx.doi.org/10.1002/jev2.12269
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author Berry, François
Morin‐Dewaele, Margot
Majidipur, Amene
Jamet, Thibaud
Bartier, Sophie
Ignjatovic, Eva
Toniutti, Donatella
Gaspar Lopes, Jeanne
Soyeux‐Porte, Pascale
Maillé, Pascale
Saldana, Carolina
Brillet, Rozenn
Ahnou, Nazim
Softic, Laurent
Couturaud, Benoit
Huet, Éric
Ahmed‐Belkacem, Abdelhakim
Fourati, Slim
Louis, Bruno
Coste, André
Béquignon, Émilie
de la Taille, Alexandre
Destouches, Damien
Vacherot, Francis
Pawlotsky, Jean‐Michel
Firlej, Virginie
Bruscella, Patrice
author_facet Berry, François
Morin‐Dewaele, Margot
Majidipur, Amene
Jamet, Thibaud
Bartier, Sophie
Ignjatovic, Eva
Toniutti, Donatella
Gaspar Lopes, Jeanne
Soyeux‐Porte, Pascale
Maillé, Pascale
Saldana, Carolina
Brillet, Rozenn
Ahnou, Nazim
Softic, Laurent
Couturaud, Benoit
Huet, Éric
Ahmed‐Belkacem, Abdelhakim
Fourati, Slim
Louis, Bruno
Coste, André
Béquignon, Émilie
de la Taille, Alexandre
Destouches, Damien
Vacherot, Francis
Pawlotsky, Jean‐Michel
Firlej, Virginie
Bruscella, Patrice
author_sort Berry, François
collection PubMed
description Small Extracellular Vesicles (sEVs) are 50–200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role of sEVs present in the mucus (mu‐sEVs) produced by human nasal epithelial cells (HNECs) in SARS‐CoV‐2 infection. We show that uninfected HNECs produce mu‐sEVs containing SARS‐CoV‐2 receptor ACE2 and activated protease TMPRSS2. mu‐sEVs cleave prefusion viral Spike proteins at the S1/S2 boundary, resulting in higher proportions of prefusion S proteins exposing their receptor binding domain in an ‘open’ conformation, thereby facilitating receptor binding at the cell surface. We show that the role of nasal mu‐sEVs is to complete prefusion Spike priming performed by intracellular furin during viral egress from infected cells. This effect is mediated by vesicular TMPRSS2 activity, rendering SARS‐CoV‐2 virions prone to entry into target cells using the ‘early’, TMPRSS2‐dependent pathway instead of the ‘late’, cathepsin‐dependent route. These results indicate that prefusion Spike priming by mu‐sEVs in the nasal cavity plays a role in viral tropism. They also show that nasal mucus does not protect from SARS‐CoV‐2 infection, but instead facilitates it.
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spelling pubmed-95877082022-10-24 Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection Berry, François Morin‐Dewaele, Margot Majidipur, Amene Jamet, Thibaud Bartier, Sophie Ignjatovic, Eva Toniutti, Donatella Gaspar Lopes, Jeanne Soyeux‐Porte, Pascale Maillé, Pascale Saldana, Carolina Brillet, Rozenn Ahnou, Nazim Softic, Laurent Couturaud, Benoit Huet, Éric Ahmed‐Belkacem, Abdelhakim Fourati, Slim Louis, Bruno Coste, André Béquignon, Émilie de la Taille, Alexandre Destouches, Damien Vacherot, Francis Pawlotsky, Jean‐Michel Firlej, Virginie Bruscella, Patrice J Extracell Vesicles Research Articles Small Extracellular Vesicles (sEVs) are 50–200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role of sEVs present in the mucus (mu‐sEVs) produced by human nasal epithelial cells (HNECs) in SARS‐CoV‐2 infection. We show that uninfected HNECs produce mu‐sEVs containing SARS‐CoV‐2 receptor ACE2 and activated protease TMPRSS2. mu‐sEVs cleave prefusion viral Spike proteins at the S1/S2 boundary, resulting in higher proportions of prefusion S proteins exposing their receptor binding domain in an ‘open’ conformation, thereby facilitating receptor binding at the cell surface. We show that the role of nasal mu‐sEVs is to complete prefusion Spike priming performed by intracellular furin during viral egress from infected cells. This effect is mediated by vesicular TMPRSS2 activity, rendering SARS‐CoV‐2 virions prone to entry into target cells using the ‘early’, TMPRSS2‐dependent pathway instead of the ‘late’, cathepsin‐dependent route. These results indicate that prefusion Spike priming by mu‐sEVs in the nasal cavity plays a role in viral tropism. They also show that nasal mucus does not protect from SARS‐CoV‐2 infection, but instead facilitates it. John Wiley and Sons Inc. 2022-10-22 2022-10 /pmc/articles/PMC9587708/ /pubmed/36271885 http://dx.doi.org/10.1002/jev2.12269 Text en © 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Berry, François
Morin‐Dewaele, Margot
Majidipur, Amene
Jamet, Thibaud
Bartier, Sophie
Ignjatovic, Eva
Toniutti, Donatella
Gaspar Lopes, Jeanne
Soyeux‐Porte, Pascale
Maillé, Pascale
Saldana, Carolina
Brillet, Rozenn
Ahnou, Nazim
Softic, Laurent
Couturaud, Benoit
Huet, Éric
Ahmed‐Belkacem, Abdelhakim
Fourati, Slim
Louis, Bruno
Coste, André
Béquignon, Émilie
de la Taille, Alexandre
Destouches, Damien
Vacherot, Francis
Pawlotsky, Jean‐Michel
Firlej, Virginie
Bruscella, Patrice
Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection
title Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection
title_full Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection
title_fullStr Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection
title_full_unstemmed Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection
title_short Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection
title_sort proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in sars‐cov‐2 infection
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587708/
https://www.ncbi.nlm.nih.gov/pubmed/36271885
http://dx.doi.org/10.1002/jev2.12269
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