biostudies-literatureLi CFood and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (HMRF)Innovation and Technology Commission (ITF)Research Grants Council, University Grants CommitteeResearch Grants Council, University Grants Committee (RGC, UGC)Innovation and Technology CommissionFood and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund10772https://www.ebi.ac.uk/biostudies/studies/S-EPMC11686133biostudies-literatureUnknown15(1)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 reNature communicationsHuman respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.PMC11686133C7042-21G1711372417105420COVID1903010-project 11CID-HKU1-3Health@InnoHKCai JPLi CHuang JChan JFWan ZYue MWong KKClevers HHuang LZhang SZhou YLiu XXue WChiu MCLan QChu HZhu XYip CCYuen KYYu YDeng YZhou JfalseHuman 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 re2024-01-01T00:00:00Z2024 Dec2026-06-01T23:19:04.585Z2025-04-05T17:00:42.568ZS-EPMC116861333973801410.1038/s41467-024-55076-2