Mary Wilson
Well-known member
Published: December 01, 2022
DOI:https://doi.org/10.1016/j.cell.2022.11.030
Chien-Ting Wu [SUP]11, [/SUP]Peter V. Lidsky [SUP]11, [/SUP]Yinghong Xiao [SUP]11, [/SUP]Carlos Milla, Raul Andino, Peter K. Jackson [SUP]12[/SUP]
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Highlights
How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary nasal epithelial organoid cultures, we found the virus attaches to motile cilia via the ACE2 receptor. SARS-CoV-2 traverses the mucus layer, using motile cilia as tracks to access the cell body. Depleting cilia blocks infection for SARS-CoV-2 and other respiratory viruses. SARS-CoV-2 progeny attach to airway microvilli 24 hours post-infection and trigger formation of apically extended and highly branched microvilli that organize viral egress from the microvilli back into the mucus layer, supporting a model of virus dispersion throughout airway tissue via mucociliary transport. Phosphoproteomics and kinase inhibition reveal microvillar remodeling is regulated by PAK kinases. Importantly, Omicron variants bind with higher affinity to motile cilia and show accelerated viral entry. Our work suggests that motile cilia, microvilli, and mucociliary-dependent mucus flow are critical for efficient virus replication in nasal epithelia.
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https://www.cell.com/cell/fulltext/S0092-8674(22)01505-7#articleInformation
DOI:https://doi.org/10.1016/j.cell.2022.11.030
Chien-Ting Wu [SUP]11, [/SUP]Peter V. Lidsky [SUP]11, [/SUP]Yinghong Xiao [SUP]11, [/SUP]Carlos Milla, Raul Andino, Peter K. Jackson [SUP]12[/SUP]
Show all authors
Highlights
- ●
SARS-CoV-2 binds ACE2 on multicilia in airway epithelia immediately upon infection - ●
Depleting motile cilia inhibits viral entry by SARS-CoV-2 and other respiratory viruses - ●
SARS-CoV-2 activates PAK kinases to rearrange airway microvilli driving viral exit - ●
Omicron variants accelerate cilia-dependent entry through the airway mucin barrier
How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary nasal epithelial organoid cultures, we found the virus attaches to motile cilia via the ACE2 receptor. SARS-CoV-2 traverses the mucus layer, using motile cilia as tracks to access the cell body. Depleting cilia blocks infection for SARS-CoV-2 and other respiratory viruses. SARS-CoV-2 progeny attach to airway microvilli 24 hours post-infection and trigger formation of apically extended and highly branched microvilli that organize viral egress from the microvilli back into the mucus layer, supporting a model of virus dispersion throughout airway tissue via mucociliary transport. Phosphoproteomics and kinase inhibition reveal microvillar remodeling is regulated by PAK kinases. Importantly, Omicron variants bind with higher affinity to motile cilia and show accelerated viral entry. Our work suggests that motile cilia, microvilli, and mucociliary-dependent mucus flow are critical for efficient virus replication in nasal epithelia.
PDF Download 138MB
https://www.cell.com/cell/fulltext/S0092-8674(22)01505-7#articleInformation