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Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction

dc.rights.licenseopenen_US
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBEUCHER, Guillaume
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBLONDOT, Marie-Lise
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorCELLE, Alexis
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPIED, Noemie
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorRECORDON-PINSON, Patricia
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorESTEVES, Pauline
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorFAURE, Muriel
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorMETIFIOT, Mathieu
dc.contributor.authorLACOMME, Sabrina
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorDACHEUX, Denis
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorROBINSON, Derrick Roy
dc.contributor.authorLANGST, Gernot
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorBEAUFILS, Fabien
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorLAFON, Marie-Edith
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorBERGER, Patrick
ORCID: 0000-0003-4702-0343
IDREF: 060717998
hal.structure.identifierInterdisciplinary Institute for Neuroscience [Bordeaux] [IINS]
dc.contributor.authorLANDRY, Marc
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierGlobal Health in the Global South [GHiGS]
dc.contributor.authorMALVY, Denis
hal.structure.identifierCentre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
dc.contributor.authorTRIAN, Thomas
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorANDREOLA, Marie-Line
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorWODRICH, Harald
dc.date.accessioned2022-10-14T13:51:36Z
dc.date.available2022-10-14T13:51:36Z
dc.date.issued2022-07-12
dc.identifier.issn1091-6490 (Electronic) 0027-8424 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/170026
dc.description.abstractEnSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epithelia from adult and child donors to follow the SARS-CoV-2 infection dynamics. We show that, in epithelia from adult donors, infections initiate in multiciliated cells and spread within 24 to 48 h throughout the whole epithelia. Syncytia formed of ciliated and basal cells appeared at the apical side of the epithelia within 3 to 4 d and were released into the apical lumen, where they contributed to the transmittable virus dose. A small number of reconstituted epithelia were intrinsically more resistant to virus infection, limiting virus spread to different degrees. This phenotype was more frequent in epithelia derived from children versus adults and correlated with an accelerated release of type III interferon. Treatment of permissive adult epithelia with exogenous type III interferon restricted infection, while type III interferon gene knockout promoted infection. Furthermore, a transcript analysis revealed that the inflammatory response was specifically attenuated in children. Taken together, our findings suggest that apical syncytia formation is an underappreciated source of virus propagation for tissue or environmental dissemination, whereas a robust type III interferon response such as commonly seen in young donors restricted SARS-CoV-2 infection. Thus, the combination of interferon restriction and attenuated inflammatory response in children might explain the epidemiological observation of age-related susceptibility to COVID-19.
dc.description.sponsorshipDéveloppment d'une infrastructure française distribuée coordonnée - ANR-10-INBS-0004en_US
dc.description.sponsorshipRôle du muscle lisse bronchique sur les exacerbations de l'asthmeen_US
dc.description.sponsorshipAlliance française contre les maladies parasitairesen_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enBronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction
dc.typeArticle de revueen_US
dc.identifier.doi10.1073/pnas.2202370119en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed35749382en_US
bordeaux.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
bordeaux.volume119en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue28en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionCNRS
bordeaux.teamGHIGS_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDAgence Nationale de la Rechercheen_US
bordeaux.identifier.funderIDFondation de Franceen_US
bordeaux.identifier.funderIDUniversité de Bordeauxen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDCentre National de la Recherche Scientifiqueen_US
hal.identifierhal-03815383
hal.version1
hal.date.transferred2022-10-14T13:51:42Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20of%20the%20United%20States%20of%20America&rft.date=2022-07-12&rft.volume=119&rft.issue=28&rft.eissn=1091-6490%20(Electronic)%200027-8424%20(Linking)&rft.issn=1091-6490%20(Electronic)%200027-8424%20(Linking)&rft.au=BEUCHER,%20Guillaume&BLONDOT,%20Marie-Lise&CELLE,%20Alexis&PIED,%20Noemie&RECORDON-PINSON,%20Patricia&rft.genre=article


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