Air-liquid interphase culture confers SARS-CoV-2 susceptibility to A549 alveolar epithelial cells

Biochem Biophys Res Commun. 2021 Sep 10;577:146-151. doi: 10.1016/j.bbrc.2021.09.015. Online ahead of print.ABSTRACTThe 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.PMID:34517212 | DOI:10.1016/j.bbrc.2021.09.015

Source: Biochemical and Biophysical Research communications - September 13, 2021 Category: Biochemistry Authors: Michihito Sasaki Mai Kishimoto Yukari Itakura Koshiro Tabata Kittiya Intaruck Kentaro Uemura Shinsuke Toba Takao Sanaki Akihiko Sato William W Hall Yasuko Orba Hirofumi Sawa Source Type: research