SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming
Chien-Ting Wu, Peter V Lidsky, Yinghong Xiao, Ran Cheng, Ivan T Lee, Tsuguhisa Nakayama, Sizun Jiang, Wei He, Janos Demeter, Miguel G Knight, Rachel E Turn, Laura S Rojas-Hernandez, Chengjin Ye, Kevin Chiem, Judy Shon, Luis Martinez-Sobrido, Carolyn R Bertozzi, Garry P Nolan, Jayakar V Nayak, Carlos Milla, Raul Andino, Peter K Jackson
Cell, doi:10.1016/j.cell.2022.11.030
Highlights d SARS-CoV-2 binds ACE2 on multicilia in airway epithelia immediately upon infection d Depleting motile cilia inhibits viral entry by SARS-CoV-2 and other respiratory viruses d SARS-CoV-2 activates PAK kinases to rearrange airway microvilli driving viral exit d Omicron variants accelerate cilia-dependent entry through the airway mucin barrier Authors
AUTHOR CONTRIBUTIONS Concept and study coordination, C.-T.W. and P.K.J. Experimental design/ execution, C.-T.W., P.L., Y.X., R.C., I.T.L., T.N., S.J., W.H., R.A., P.K.J., R.E.T., and M.G.K. Microscopy, C.-T.W., IHC, I.T.L., and T.N. Virus production/human nasal epithelial cell infection, C.-T.W., P.L., Y.X., M.G.K., K.C., J.S. T.W. with help from I.T.L., S.J., and G.P.N. Funding/scientific guidance, R.A. and P.K.J. All authors reviewed the manuscript.
DECLARATION OF INTERESTS The authors declare no competing interests.
KEY RESOURCES
Lead contact Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Peter Jackson (pjackson@stanford.edu).
Materials availability This study did not generate new unique reagents.
Data and code availability The analysis code used to support the findings of this study are available at https://doi.org/10.5281/zenodo.7343831.
EXPERIMENTAL MODEL AND SUBJECT DETAILS Primary human nasal cell culture Human tracheobronchial epithelial cells were obtained from patients who underwent bronchoscopy or surgical lung resection during diagnostic procedures for pulmonary diseases at Stanford (Tables S1 and S2 ). Nasal epithelial cultures were generated using an already well-established protocol in our laboratories. 28 After obtaining informed consent (Stanford IRB protocol #42710), subjects underwent brushing of the inferior turbinate from both nasal cavities to obtain a cell..
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