SARS-CoV-2 infection and replication in human gastric organoids
| Autor: | Hans Clevers, Camilla Luni, Giovanni Giuseppe Giobbe, Anna Manfredi, Lucio Di Filippo, Matteo Pagliari, Vivian S. W. Li, Brendan C. Jones, Paolo De Coppi, Hannah T. Stuart, Francesco Bonfante, Valentina Panzarin, Nikhil Thapar, Alessio Bortolami, Onelia Gagliano, Silvia Perin, Alessandro Filippo Pellegata, Georg A. Busslinger, Davide Cacchiarelli, Elisa Zambaiti, Cecilia Laterza, Simon Eaton, Eva Mazzetto, Chiara Colantuono, Nicola Elvassore |
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| Přispěvatelé: | Giobbe, Giovanni Giuseppe, Bonfante, Francesco, Jones, Brendan C., Gagliano, Onelia, Luni, Camilla, Zambaiti, Elisa, Perin, Silvia, Laterza, Cecilia, Busslinger, Georg, Stuart, Hannah, Pagliari, Matteo, Bortolami, Alessio, Mazzetto, Eva, Manfredi, Anna, Colantuono, Chiara, Di Filippo, Lucio, Pellegata, Alessandro Filippo, Panzarin, Valentina, Thapar, Nikhil, Li, Vivian Sze Wing, Eaton, Simon, Cacchiarelli, Davide, Clevers, Han, Elvassore, Nicola, De Coppi, Paolo, Giobbe, G. G., Bonfante, F., Jones, B. C., Gagliano, O., Luni, C., Zambaiti, E., Perin, S., Laterza, C., Busslinger, G., Stuart, H., Pagliari, M., Bortolami, A., Mazzetto, E., Manfredi, A., Colantuono, C., Di Filippo, L., Pellegata, A. F., Panzarin, V., Thapar, N., Li, V. S. W., Eaton, S., Cacchiarelli, D., Clevers, H., Elvassore, N., De Coppi, P., Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Organoid
Virus Replication/physiology General Physics and Astronomy Aborted Fetu CHILDREN organoid stomach gastric epithelium COVID transcriptomic Virus Replication Transcriptome 0302 clinical medicine Interferon Chlorocebus aethiops Gastrointestinal models Intestinal Mucosa CYTOSCAPE Child Adult stem cells 0303 health sciences Multidisciplinary Stomach SARS-CoV-2/isolation & purification digestive oral and skin physiology food and beverages EXPANSION Stomach/pathology Middle Aged 3. Good health Multidisciplinary Sciences Organoids medicine.anatomical_structure 030220 oncology & carcinogenesis Child Preschool Aborted Fetus Science & Technology - Other Topics STEM-CELLS medicine.drug Human Science Biology Chlorocebus aethiop General Biochemistry Genetics and Molecular Biology Virus Article Cell Line 03 medical and health sciences COVID-19/pathology medicine Animals Humans Viral shedding Aged COVID-19 Infant SARS-CoV-2 Preschool 030304 developmental biology Fetus Science & Technology Intestinal Mucosa/pathology Animal General Chemistry MODEL Organoids/pathology Viral replication Viral infection Immunology RNA |
| Zdroj: | Nature Communications Nature Communications, 12(1). Nature Publishing Group Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2041-1723 |
| Popis: | COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission. Several clinical reports have described gastrointestinal symptoms for COVID-19, though whether the virus can replicate within the stomach remains unclear. Here the authors generate gastric organoids from human biopsies and show that the virus can efficiently infect gastric epithelium, suggesting that the stomach might have an active role in fecal-oral transmission. |
| Databáze: | OpenAIRE |
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