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J. Med. Virol., Apr 2024, 96 (4) | https://doi.org/10.1002/jmv.29600 Differential beta-coronavirus infection dynamics in human bronchial epithelial organoids

Dongbin Park¹, Se‐Mi Kim¹, Hobin Jang¹, Kanghee Kim^1,2, Ho young Ji¹, Heedong Yang², Woohyun Kwon^1,2, Yeonglim Kang¹, Suhee Hwang¹, Hyunjoon Kim¹, Mark Anthony B. Casel^1,2, Issac Choi¹, Jeong‐Sun Yang³, Joo‐Yeon Lee³, Young Ki Choi^1,2

¹Center for Study of Emerging and Re‐emerging Viruses, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon, Republic of Korea

²College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea

³Division of Viral Diseases, Center for Laboratory Control of Infectious Disease, Korea National Institute of Health (KNIH), Cheongju, Republic of Korea

Dongbin Park and Se-Mi Kim authors contributed equally to this study.

Correspondence : Young Ki Choi

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.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-12)
연구진국내 연구진
분야 의약학 > 감염의학

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