Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction
The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention. Nasal organoids are more susceptible to HRV-C than airway organoids. Intriguingly, upon HRV-C infection, we observe an innate immune response that is stronger in airway organoids than in nasal organoids, which is reproduced in a Poly(I:C) stimulation assay. Treatment with α-CDHR3 and antivirals significantly reduces HRV-C viral growth in airway and nasal organoids. Additionally, an organoid-based immunofluorescence assay is established to titrate HRV-C infectious particles. Collectively, we develop an organoid-based system to reproducibly propagate the poorly cultivable HRV-C, followed by a comprehensive characterization of HRV-C infection and innate immunity in physiologically active respiratory organoids. The organoid-based HRV-C infection model can be extended for developing antiviral strategies. More importantly, our study has opened an avenue for propagating and studying other uncultivable human and animal viruses.
Authors
- Jie Zhou (ORCID: https://orcid.org/0000-0002-2948-3873)
- Lin Huang (ORCID: https://orcid.org/0000-0003-4753-3683)
- Yanlin Deng
- Weiwei Xue (ORCID: https://orcid.org/0000-0002-3285-0574)
- Ming Yue (ORCID: https://orcid.org/0000-0002-4052-818X)
- Man Chun Chiu (ORCID: https://orcid.org/0000-0001-9503-6396)
- Yifei Yu (ORCID: https://orcid.org/0000-0002-8677-4650)
- Yu Yang (ORCID: https://orcid.org/0000-0002-4663-9753)
- Hin Chu (ORCID: https://orcid.org/0000-0003-2855-9837)
- Jasper Fuk‐Woo Chan (ORCID: https://orcid.org/0000-0001-6336-6657)
- Cyril Chik‐Yan Yip (ORCID: https://orcid.org/0000-0002-9606-8506)
- Hans Clevers (ORCID: https://orcid.org/0000-0002-3077-5582)
- Zhixin Wan
- Qiaoshuai Lan (ORCID: https://orcid.org/0000-0001-5524-3542)
- Jian‐Piao Cai (ORCID: https://orcid.org/0000-0003-4077-3852)
- Kwok‐Yung Yuen (ORCID: https://orcid.org/0000-0002-2083-1552)
- Shuxin Zhang (ORCID: https://orcid.org/0000-0002-3798-6964)
- Ying Zhou (ORCID: https://orcid.org/0000-0002-3516-5097)
- Cun Li (ORCID: https://orcid.org/0000-0003-3003-0000)
- Xiaoxin Zhu (ORCID: https://orcid.org/0000-0003-2948-3395)
- Jingjing Huang (ORCID: https://orcid.org/0000-0003-0723-7716)
- Xiaojuan Liu (ORCID: https://orcid.org/0000-0002-4965-1264)
- Kenneth Kak‐Yuen Wong (ORCID: https://orcid.org/0000-0001-7371-503X)
Institutions
- Roche (Switzerland) (CH)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Peking University (CN)
- Queen Mary Hospital (CN)
- Hong Kong Science and Technology Parks Corporation (HK)
- University Medical Center Utrecht (NL)
- Oncode Institute (NL)
- Peking University Third Hospital (CN)
- HKU-Pasteur Research Pole (HK)
- Hanshan Normal University (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-55076-2
- Citations
- 18
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 6.96
Funders
- Research Grants Council, University Grants Committee
- Innovation and Technology Commission
- Food and Health Bureau
- Health and Medical Research Fund