1. Air-liquid interphase culture confers SARS-CoV-2 susceptibility to A549 alveolar epithelial cells.
- Author
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Sasaki M, Kishimoto M, Itakura Y, Tabata K, Intaruck K, Uemura K, Toba S, Sanaki T, Sato A, Hall WW, Orba Y, and Sawa H
- Subjects
- A549 Cells, Alveolar Epithelial Cells pathology, Cells, Cultured, Disease Susceptibility, Gene Expression Regulation, Neoplastic, Humans, Peptidyl-Dipeptidase A genetics, Peptidyl-Dipeptidase A metabolism, Serine Endopeptidases genetics, Serine Endopeptidases metabolism, Up-Regulation genetics, Alveolar Epithelial Cells virology, COVID-19 virology, Cell Culture Techniques methods, SARS-CoV-2 physiology
- Abstract
The human lung cell A549 is susceptible to infection with a number of respiratory viruses. However, A549 cells are resistant to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection in conventional submerged culture, and this would appear to be due to low expression levels of the SARS-CoV-2 entry receptor: angiotensin-converting enzyme-2 (ACE2). Here, we examined SARS-CoV-2 susceptibility to A549 cells after adaptation to air-liquid interface (ALI) culture. A549 cells in ALI culture yielded a layer of mucus on their apical surface, exhibited decreased expression levels of the proliferation marker KI-67 and intriguingly became susceptible to SARS-CoV-2 infection. We found that A549 cells increased the endogenous expression levels of ACE2 and TMPRSS2 following adaptation to ALI culture conditions. Camostat, a TMPRSS2 inhibitor, reduced SARS-CoV-2 infection in ALI-cultured A549 cells. These findings indicate that ALI culture switches the phenotype of A549 cells from resistance to susceptibility to SARS-CoV-2 infection through upregulation of ACE2 and TMPRSS2., Competing Interests: Declaration of competing interest Kentaro Uemura, Shinsuke Toba, Takao Sanaki and Akihiko Sato are employees of Shionogi & Co., Ltd. Other authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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