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dc.contributor.authorPinto, Andreia L
dc.contributor.authorRai, Ranjit K
dc.contributor.authorBrown, Jonathan C
dc.contributor.authorGriffin, Paul
dc.contributor.authorEdgar, James R
dc.contributor.authorShah, Anand
dc.contributor.authorSinganayagam, Aran
dc.contributor.authorHogg, Claire
dc.contributor.authorBarclay, Wendy S
dc.contributor.authorFutter, Clare E
dc.contributor.authorBurgoyne, Thomas
dc.date.accessioned2022-04-27T01:02:03Z
dc.date.available2022-04-27T01:02:03Z
dc.date.issued2022-03-25
dc.identifier.issn2041-1723
dc.identifier.other35338134
dc.identifier.otherPMC8956608
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336494
dc.descriptionFunder: G2P-UK National Virology Consortium funded by UKRI
dc.description.abstractUltrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Here, we examined human airway epithelium infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistently, extracellular virions were seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion where tomography showed that the viral membrane was continuous with the apical plasma membrane and the nucleocapsids diluted, compared with unfused virus, demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Tomography showed concentration of nucleocapsids round the periphery of profiles strongly suggestive of viral budding into these compartments and this may explain how virions gain their S glycoprotein containing envelope.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101528555
dc.sourceessn: 2041-1723
dc.subjectEpithelium
dc.subjectHumans
dc.subjectPeptidyl-Dipeptidase A
dc.subjectCOVID-19
dc.subjectSARS-CoV-2
dc.titleUltrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium.
dc.typeArticle
dc.date.updated2022-04-27T01:02:01Z
prism.issueIdentifier1
prism.publicationNameNature communications
prism.volume13
dc.identifier.doi10.17863/CAM.83912
rioxxterms.versionofrecord10.1038/s41467-022-29255-y
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBrown, Jonathan C [0000-0001-6849-3962]
dc.contributor.orcidEdgar, James R [0000-0001-7903-8199]
dc.contributor.orcidSinganayagam, Aran [0000-0001-9849-0033]
dc.contributor.orcidHogg, Claire [0000-0002-8368-5994]
dc.contributor.orcidBarclay, Wendy S [0000-0002-3948-0895]
dc.contributor.orcidBurgoyne, Thomas [0000-0002-8428-720X]
pubs.funder-project-idWellcome Trust (093445, 216370/Z/19/Z)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International