Differentiated human airway organoids to assess infectivity of emerging influenza virus
| Autor: | Dong Wang, Shuofeng Yuan, Hin Chu, Bosco Ho-Yin Wong, Cun Li, Hans Clevers, Norman Sachs, Kwok-Yung Yuen, Xiaoyu Zhao, Wenjun Song, Kelvin K. W. To, Jasper Fuk-Woo Chan, Honglin Chen, Lei Wen, Man Chun Chiu, Jie Zhou, Vincent Kwok-Man Poon, Kenneth K. Y. Wong |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Respiratory System/pathology Proteases viruses Respiratory System Airway organoid H1N1 Subtype/growth & development Biology medicine.disease_cause Microbiology Virus 03 medical and health sciences Influenza A Virus H1N1 Subtype 0302 clinical medicine Influenza Human Influenza A Virus medicine Organoid Humans Infectivity Influenza A Virus H7N2 Subtype/growth & development Multidisciplinary Cilium respiratory system Biological Sciences Influenza A Virus H7N2 Subtype Proximal differentiation Virology Influenza Influenza A virus subtype H5N1 Epithelium Organoids H7N2 Subtype/growth & development Organoids/pathology Titer 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Influenza A Virus H1N1 Subtype/growth & development Influenza virus Human |
| Zdroj: | Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America, 115(26), 6822 Proceedings of the National Academy of Sciences of the United States of America, 115(26), 6822-6827. National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance Influenza virus infection represents a major threat to public health worldwide. There is no biologically relevant, reproducible, and readily available in vitro model for predicting the infectivity of influenza viruses in humans. Based on the long-term expanding 3D human airway organoids, we developed proximal differentiation and further established a 2D monolayer culture of airway organoids. The resultant 3D and 2D proximal differentiated airway organoids can morphologically and functionally simulate human airway epithelium and as a proof of concept can discriminate human-infective influenza viruses from poorly human-infective viruses. Thus, the proximal differentiated airway organoids can be utilized to predict the infectivity of influenza viruses and, more broadly, provide a universal platform for studying the biology and pathology of the human airway. Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid. In addition, the differentiation conditions induce elevated levels of serine proteases, which are essential for productive infection of human influenza viruses and low-pathogenic avian influenza viruses. We also established improved 2D monolayer culture conditions for the differentiated airway organoids. To demonstrate the ability of differentiated airway organoids to identify human-infective virus, 3D and 2D differentiated airway organoids are applied to evaluate two pairs of viruses with known distinct infectivity in humans, H7N9/Ah versus H7N2 and H1N1pdm versus an H1N1 strain isolated from swine (H1N1sw). The human-infective H7N9/Ah virus replicated more robustly than the poorly human-infective H7N2 virus; the highly human-infective H1N1pdm virus replicated to a higher titer than the counterpart H1N1sw. Collectively, we developed differentiated human airway organoids which can morphologically and functionally simulate human airway epithelium. These differentiated airway organoids can be applied for rapid assessment of the infectivity of emerging respiratory viruses to human. |
| Databáze: | OpenAIRE |
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