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 MillaRaul Andino, Peter K. Jackson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 that 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 h 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 that microvillar remodeling is regulated by p21-activated kinases (PAK). 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.

Original languageEnglish (US)
Pages (from-to)112-130.e20
Issue number1
StatePublished - Jan 5 2023
Externally publishedYes


  • airway epithelial cells
  • cilia
  • COVID-19
  • microvilli
  • organoids
  • protein kinases
  • proteomics
  • respiratory synctital virus
  • respiratory virus
  • SARS-CoV-2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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