@article{5016,
  keywords = {Respiratory Tract Diseases, Viral pathogenesis, Virus–host interactions},
  author = {Cun Li and Yifei Yu and Zhixin Wan and Man Chun Chiu and Jingjing Huang and Shuxin Zhang and Xiaoxin Zhu and Qiaoshuai Lan and Yanlin Deng and Ying Zhou and Wei Xue and Ming Yue and Jian-Piao Cai and Cyril Chik-Yan Yip and Kenneth Kak-Yuen Wong and Xiaojuan Liu and Yang Yu and Lin Huang and Hin Chu and Jasper Fuk-Woo Chan and Hans Clevers and Kwok Yung Yuen and Jie Zhou},
  title = {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, 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.},
  year = {2024},
  journal = {Nature Communications},
  volume = {15},
  pages = {10772},
  month = {2024-12-30},
  issn = {2041-1723},
  url = {https://www.nature.com/articles/s41467-024-55076-2},
  doi = {10.1038/s41467-024-55076-2},
  language = {en},
}