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Differential beta-coronavirus infection dynamics in human bronchial epithelial organoids

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Title
Differential beta-coronavirus infection dynamics in human bronchial epithelial organoids
Author(s)
Dongbin Park; Se-Mi Kim; Hobin Jang; Kanghee Kim; Ho young Ji; Yang, Heedong; Woohyun Kwon; Yeonglim Kang; Suhee Hwang; Hyunjoon Kim; Mark Anthony B. Casel; Issac Choi; Yang, Jeong-Sun; Lee, Joo-Yeon; Young Ki Choi
Publication Date
2024-04
Journal
Journal of Medical Virology, v.96, no.4
Publisher
John Wiley & Sons Inc.
Abstract
The lower respiratory system serves as the target and barrier for beta-coronavirus (beta-CoV) infections. In this study, we explored beta-CoV infection dynamics in human bronchial epithelial (HBE) organoids, focusing on HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2. Utilizing advanced organoid culture techniques, we observed robust replication for all beta-CoVs, particularly noting that SARS-CoV-2 reached peak viral RNA levels at 72 h postinfection. Through comprehensive transcriptomic analysis, we identified significant shifts in cell population dynamics, marked by an increase in goblet cells and a concurrent decrease in ciliated cells. Furthermore, our cell tropism analysis unveiled distinct preferences in viral targeting: HCoV-OC43 predominantly infected club cells, while SARS-CoV had a dual tropism for goblet and ciliated cells. In contrast, SARS-CoV-2 primarily infected ciliated cells, and MERS-CoV showed a marked affinity for goblet cells. Host factor analysis revealed the upregulation of genes encoding viral receptors and proteases. Notably, HCoV-OC43 induced the unfolded protein response pathway, which may facilitate viral replication. Our study also reveals a complex interplay between inflammatory pathways and the suppression of interferon responses during beta-CoV infections. These findings provide insights into host-virus interactions and antiviral defense mechanisms, contributing to our understanding of beta-CoV infections in the respiratory tract. © 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.
URI
https://pr.ibs.re.kr/handle/8788114/15113
DOI
10.1002/jmv.29600
ISSN
0146-6615
Appears in Collections:
Korea Virus Research Institute(한국바이러스기초연구소) > Center for Study of Emerging and Re-emerging Viruses(신변종 바이러스 연구센터) > 1. Journal Papers (저널논문)
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