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SARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia

dc.rights.licenseopenen_US
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBEUCHER, Guillaume
dc.contributor.authorBLONDOT, Marie-Lise
dc.contributor.authorCELLE, Alexis
dc.contributor.authorPIED, Noémie
dc.contributor.authorRECORDON-PINSON, Patricia
dc.contributor.authorESTEVES, Pauline
dc.contributor.authorFAURE, Muriel
dc.contributor.authorMÉTIFIOT, Mathieu
dc.contributor.authorLACOMME, Sabrina
dc.contributor.authorDACHEAUX, Denis
dc.contributor.authorROBINSON, Derrick R
dc.contributor.authorLÄNGST, Gernot
dc.contributor.authorBEAUFILS, Fabien
dc.contributor.authorLAFON, Marie-Edith
dc.contributor.authorBERGER, Patrick
dc.contributor.authorLANDRY, Marc
dc.contributor.authorMALVY, Denis
dc.contributor.authorTRIAN, Thomas
dc.contributor.authorANDREOLA, Marie-Line
dc.contributor.authorWODRICH, Harald
dc.date.accessioned2023-05-24T14:27:52Z
dc.date.available2023-05-24T14:27:52Z
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182329
dc.description.abstractEnThe 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 Statement Bronchial 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.
dc.language.isoENen_US
dc.subject.enSARS-CoV-2
dc.subject.enhuman bronchial epithelia
dc.subject.enAge
dc.subject.enSyncytia formation
dc.subject.enIFN response
dc.title.enSARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1101/2021.05.28.446159en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologieen_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.institutionCNRSen_US
bordeaux.import.sourcehal
hal.identifierhal-03375199
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=BEUCHER,%20Guillaume&BLONDOT,%20Marie-Lise&CELLE,%20Alexis&PIED,%20No%C3%A9mie&RECORDON-PINSON,%20Patricia&rft.genre=preprint


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