Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction
Abstract 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,...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55076-2 |
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| author | Cun Li Yifei Yu Zhixin Wan Man Chun Chiu Jingjing Huang Shuxin Zhang Xiaoxin Zhu Qiaoshuai Lan Yanlin Deng Ying Zhou Wei Xue Ming Yue Jian-Piao Cai Cyril Chik-Yan Yip Kenneth Kak-Yuen Wong Xiaojuan Liu Yang Yu Lin Huang Hin Chu Jasper Fuk-Woo Chan Hans Clevers Kwok Yung Yuen Jie Zhou |
| author_facet | Cun Li Yifei Yu Zhixin Wan Man Chun Chiu Jingjing Huang Shuxin Zhang Xiaoxin Zhu Qiaoshuai Lan Yanlin Deng Ying Zhou Wei Xue Ming Yue Jian-Piao Cai Cyril Chik-Yan Yip Kenneth Kak-Yuen Wong Xiaojuan Liu Yang Yu Lin Huang Hin Chu Jasper Fuk-Woo Chan Hans Clevers Kwok Yung Yuen Jie Zhou |
| author_sort | Cun Li |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-c526a7551dd44a15b1b0a8fe0d911da8 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c526a7551dd44a15b1b0a8fe0d911da82025-01-05T12:36:31ZengNature PortfolioNature Communications2041-17232024-12-0115111310.1038/s41467-024-55076-2Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interactionCun Li0Yifei Yu1Zhixin Wan2Man Chun Chiu3Jingjing Huang4Shuxin Zhang5Xiaoxin Zhu6Qiaoshuai Lan7Yanlin Deng8Ying Zhou9Wei Xue10Ming Yue11Jian-Piao Cai12Cyril Chik-Yan Yip13Kenneth Kak-Yuen Wong14Xiaojuan Liu15Yang Yu16Lin Huang17Hin Chu18Jasper Fuk-Woo Chan19Hans Clevers20Kwok Yung Yuen21Jie Zhou22Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and Queen Mary HospitalClinical Stem Cell Research Center, Peking University Third HospitalClinical Stem Cell Research Center, Peking University Third HospitalBiomOrgan LtdDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), and University Medical Center (UMC) UtrechtDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamAbstract 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.https://doi.org/10.1038/s41467-024-55076-2 |
| spellingShingle | Cun Li Yifei Yu Zhixin Wan Man Chun Chiu Jingjing Huang Shuxin Zhang Xiaoxin Zhu Qiaoshuai Lan Yanlin Deng Ying Zhou Wei Xue Ming Yue Jian-Piao Cai Cyril Chik-Yan Yip Kenneth Kak-Yuen Wong Xiaojuan Liu Yang Yu Lin Huang Hin Chu Jasper Fuk-Woo Chan Hans Clevers Kwok Yung Yuen Jie Zhou Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction Nature Communications |
| title | Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction |
| title_full | Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction |
| title_fullStr | Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction |
| title_full_unstemmed | Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction |
| title_short | Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction |
| title_sort | human respiratory organoids sustained reproducible propagation of human rhinovirus c and elucidation of virus host interaction |
| url | https://doi.org/10.1038/s41467-024-55076-2 |
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