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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 cilia in vivo . This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.
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Preprints, Working Papers, ...
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Submitted on : Tuesday, June 1, 2021 - 11:13:14 AM
Last modification on : Thursday, April 7, 2022 - 10:10:54 AM
Long-term archiving on: : Thursday, September 2, 2021 - 6:31:45 PM


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Rémy Robinot, Mathieu Hubert, Guilherme Dias de Melo, Françoise Lazarini, Timothée Bruel, et al.. SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance. 2021. ⟨pasteur-03244406⟩



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