TY - JOUR
KW - Respiratory Tract Diseases
KW - Viral pathogenesis
KW - Virus–host interactions
AU - Cun Li
AU - Yifei Yu
AU - Zhixin Wan
AU - Man Chun Chiu
AU - Jingjing Huang
AU - Shuxin Zhang
AU - Xiaoxin Zhu
AU - Qiaoshuai Lan
AU - Yanlin Deng
AU - Ying Zhou
AU - Wei Xue
AU - Ming Yue
AU - Jian-Piao Cai
AU - Cyril Chik-Yan Yip
AU - Kenneth Kak-Yuen Wong
AU - Xiaojuan Liu
AU - Yang Yu
AU - Lin Huang
AU - Hin Chu
AU - Jasper Fuk-Woo Chan
AU - Hans Clevers
AU - Kwok Yung Yuen
AU - Jie Zhou
AB - 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.
BT - Nature Communications
DA - 2024-12-30
DO - 10.1038/s41467-024-55076-2
IS - 1
LA - en
N2 - 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.
PY - 2024
EP - 10772
T2 - Nature Communications
TI - Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction
UR - https://www.nature.com/articles/s41467-024-55076-2
VL - 15
Y2 - 2025-01-15
SN - 2041-1723
ER -