Cell response analysis in SARS-CoV-2 infected bronchial organoids
Emi Sano, Tatsuya Suzuki, Rina Hashimoto, Yumi Itoh, Ayaka Sakamoto, Yusuke Sakai, Akatsuki Saito, Daisuke Okuzaki, Daisuke Motooka, Yukiko Muramoto, Takeshi Noda, Tomohiko Takasaki, Jun-ichi Sakuragi, Shohei Minami, Takeshi Kobayashi, Takuya Yamamoto, Yasufumi Matsumura, Miki Nagao, Toru Okamoto, Kazuo Takayama
Abstract
The development of an in vitro cell model that can be used to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research is expected. Here we conducted infection experiments in bronchial organoids (BO) and an BO-derived air-liquid interface model (BO-ALI) using 8 SARS-CoV-2 variants. The infection efficiency in BO-ALI was more than 1,000 times higher than that in BO. Among the bronchial epithelial cells, we found that ciliated cells were infected with the virus, but basal cells were not. Ciliated cells died 7 days after the viral infection, but basal cells survived after the viral infection and differentiated into ciliated cells. Fibroblast growth factor 10 signaling was essential for this differentiation. These results indicate that BO and BO-ALI may be used not only to evaluate the cell response to SARS-CoV-2 and coronavirus disease 2019 (COVID-19) therapeutic agents, but also for airway regeneration studies.