SARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia
| Autor: | Marie-Lise Blondot, Marc Landry, A. Celle, Pauline Esteves, Patrick Berger, Harald Wodrich, Patricia Recordon-Pinson, Marie-Edith Lafon, Marie-Line Andreola, Derrick R. Robinson, Fabien Beaufils, Thomas Trian, Denis Malvy, Mathieu Métifiot, Noémie Pied, Denis Dacheaux, Muriel Faure, Guillaume Beucher, Gernot Längst, Sabrina Lacomme |
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| Přispěvatelé: | Microbiologie Fondamentale et Pathogénicité [Bordeaux] (MFP), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
viruses
human bronchial epithelia Biology Virus 03 medical and health sciences Basal (phylogenetics) IFN response Age medicine Respiratory system 030304 developmental biology Infectivity 0303 health sciences Syncytium 030306 microbiology Transmission (medicine) SARS-CoV-2 Infectious dose respiratory system 3. Good health respiratory tract diseases Syncytia formation medicine.anatomical_structure Immunology [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Respiratory tract |
| Popis: | The beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted primary bronchial epithelia from adult and children donors to follow the infection dynamic following infection with SARS-CoV-2. We show that in bronchial epithelia derived from adult donors, infections initiate in multi-ciliated cells. Then, infection rapidly spread within 24-48h throughout the whole epithelia. Within 3-4 days, large apical syncytia form between multi-ciliated cells and basal cells, which dissipate into the apical lumen. We show that these syncytia are a significant source of the released infectious dose. In stark contrast to these findings, bronchial epithelia reconstituted from children donors are intrinsically more resistant to virus infection and show active restriction of virus spread. This restriction is paired with accelerated release of IFN compared to adult donors. Taken together our findings reveal apical syncytia formation as an underappreciated source of infectious virus for either local dissemination or release into the environment. Furthermore, we provide direct evidence that children bronchial epithelia are more resistant to infection with SARS-CoV-2 providing experimental support for epidemiological observations that SARS-CoV-2 cases’ fatality is linked to age.Significance StatementBronchial epithelia are the primary target for SARS-CoV-2 infections. Our work uses reconstituted bronchial epithelia from adults and children. We show that infection of adult epithelia with SARS-CoV-2 is rapid and results in the synchronized release of large clusters of infected cells and syncytia into the apical lumen contributing to the released infectious virus dose. Infection of children derived bronchial epithelia revealed an intrinsic resistance to infection and virus spread, probably as a result of a faster onset of interferon secretion. Thus, our data provide direct evidence for the epidemiological observation that children are less susceptible to SARS-CoV-2. |
| Databáze: | OpenAIRE |
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