SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance
ABSTRACT Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. We examined the functional and structural consequences of SARS-CoV-2 infection in a reconstituted human bronchial epithelium model. SARS-CoV-2 replication caused a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remained limited. Rather, SARS-CoV-2 replication led to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. The motile cilia function was compromised, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramped up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrated the loss of motile ciliain vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma..
Medienart: |
Preprint |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
bioRxiv.org - (2022) vom: 22. Nov. Zur Gesamtaufnahme - year:2022 |
---|
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Robinot, Rémy [VerfasserIn] |
---|
Links: |
Volltext [kostenfrei] |
---|
Themen: |
---|
doi: |
10.1101/2020.10.06.328369 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
XBI019080891 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | XBI019080891 | ||
003 | DE-627 | ||
005 | 20230429092214.0 | ||
007 | cr uuu---uuuuu | ||
008 | 201010s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1101/2020.10.06.328369 |2 doi | |
035 | |a (DE-627)XBI019080891 | ||
035 | |a (biorXiv)10.1101/2020.10.06.328369 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Robinot, Rémy |e verfasserin |4 aut | |
245 | 1 | 0 | |a SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a ABSTRACT Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. We examined the functional and structural consequences of SARS-CoV-2 infection in a reconstituted human bronchial epithelium model. SARS-CoV-2 replication caused a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remained limited. Rather, SARS-CoV-2 replication led to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. The motile cilia function was compromised, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramped up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrated the loss of motile ciliain vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma. | ||
650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
700 | 1 | |a Hubert, Mathieu |e verfasserin |4 aut | |
700 | 1 | |a de Melo, Guilherme Dias |e verfasserin |4 aut | |
700 | 1 | |a Lazarini, Françoise |e verfasserin |4 aut | |
700 | 1 | |a Bruel, Timothée |e verfasserin |4 aut | |
700 | 1 | |a Smith, Nikaïa |e verfasserin |4 aut | |
700 | 1 | |a Levallois, Sylvain |e verfasserin |4 aut | |
700 | 1 | |a Larrous, Florence |e verfasserin |4 aut | |
700 | 1 | |a Fernandes, Julien |e verfasserin |4 aut | |
700 | 1 | |a Gellenoncourt, Stacy |e verfasserin |4 aut | |
700 | 1 | |a Rigaud, Stéphane |e verfasserin |4 aut | |
700 | 1 | |a Gorgette, Olivier |e verfasserin |4 aut | |
700 | 1 | |a Thouvenot, Catherine |e verfasserin |4 aut | |
700 | 1 | |a Trébeau, Céline |e verfasserin |4 aut | |
700 | 1 | |a Mallet, Adeline |e verfasserin |4 aut | |
700 | 1 | |a Duménil, Guillaume |e verfasserin |4 aut | |
700 | 1 | |a Gobaa, Samy |e verfasserin |4 aut | |
700 | 1 | |a Etournay, Raphaël |e verfasserin |4 aut | |
700 | 1 | |a Lledo, Pierre-Marie |e verfasserin |4 aut | |
700 | 1 | |a Lecuit, Marc |e verfasserin |4 aut | |
700 | 1 | |a Bourhy, Hervé |e verfasserin |4 aut | |
700 | 1 | |a Duffy, Darragh |e verfasserin |4 aut | |
700 | 1 | |a Michel, Vincent |e verfasserin |4 aut | |
700 | 1 | |a Schwartz, Olivier |e verfasserin |4 aut | |
700 | 1 | |a Chakrabarti, Lisa A. |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2022) vom: 22. Nov. |
773 | 1 | 8 | |g year:2022 |g day:22 |g month:11 |
856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.10.06.328369 |z kostenfrei |3 Volltext |
912 | |a GBV_XBI | ||
912 | |a SSG-OLC-PHA | ||
951 | |a AR | ||
952 | |j 2022 |b 22 |c 11 |