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Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction

Author

Listed:
  • Cun Li

    (Pokfulam)

  • Yifei Yu

    (Pokfulam)

  • Zhixin Wan

    (Pokfulam)

  • Man Chun Chiu

    (Pokfulam
    Hong Kong Science and Technology Park)

  • Jingjing Huang

    (Pokfulam
    Hong Kong Science and Technology Park)

  • Shuxin Zhang

    (Pokfulam)

  • Xiaoxin Zhu

    (Pokfulam
    Hong Kong Science and Technology Park)

  • Qiaoshuai Lan

    (Pokfulam
    Hong Kong Science and Technology Park)

  • Yanlin Deng

    (Pokfulam
    Hong Kong Science and Technology Park)

  • Ying Zhou

    (Pokfulam)

  • Wei Xue

    (Pokfulam)

  • Ming Yue

    (Pokfulam)

  • Jian-Piao Cai

    (Pokfulam)

  • Cyril Chik-Yan Yip

    (Pokfulam)

  • Kenneth Kak-Yuen Wong

    (and Queen Mary Hospital)

  • Xiaojuan Liu

    (Peking University Third Hospital)

  • Yang Yu

    (Peking University Third Hospital)

  • Lin Huang

    (BiomOrgan Ltd)

  • Hin Chu

    (Pokfulam
    Hong Kong Science and Technology Park
    The University of Hong Kong)

  • Jasper Fuk-Woo Chan

    (Pokfulam
    Hong Kong Science and Technology Park
    The University of Hong Kong
    Pokfulam)

  • Hans Clevers

    (and University Medical Center (UMC) Utrecht
    Roche Pharmaceutical Research and Early Development)

  • Kwok Yung Yuen

    (Pokfulam
    Hong Kong Science and Technology Park
    The University of Hong Kong
    Pokfulam)

  • Jie Zhou

    (Pokfulam
    Hong Kong Science and Technology Park
    BiomOrgan Ltd
    The University of Hong Kong)

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.

Suggested Citation

  • 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 & Kenne, 2024. "Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55076-2
    DOI: 10.1038/s41467-024-55076-2
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    References listed on IDEAS

    as
    1. Toshiro Sato & Robert G. Vries & Hugo J. Snippert & Marc van de Wetering & Nick Barker & Daniel E. Stange & Johan H. van Es & Arie Abo & Pekka Kujala & Peter J. Peters & Hans Clevers, 2009. "Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche," Nature, Nature, vol. 459(7244), pages 262-265, May.
    2. Smriti Mallapaty, 2021. "The mini lungs and other organoids helping to beat COVID," Nature, Nature, vol. 593(7860), pages 492-494, May.
    3. Kyle J. Travaglini & Ahmad N. Nabhan & Lolita Penland & Rahul Sinha & Astrid Gillich & Rene V. Sit & Stephen Chang & Stephanie D. Conley & Yasuo Mori & Jun Seita & Gerald J. Berry & Joseph B. Shrager , 2020. "A molecular cell atlas of the human lung from single-cell RNA sequencing," Nature, Nature, vol. 587(7835), pages 619-625, November.
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