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dc.contributor.authorWilliams, Thomas L
dc.contributor.authorStrachan, Gregory
dc.contributor.authorMacrae, Robyn GC
dc.contributor.authorKuc, Rhoda E
dc.contributor.authorNyimanu, Duuamene
dc.contributor.authorPaterson, Anna L
dc.contributor.authorSinha, Sanjay
dc.contributor.authorMaguire, Janet
dc.contributor.authorDavenport, Anthony
dc.date.accessioned2021-12-03T00:30:12Z
dc.date.available2021-12-03T00:30:12Z
dc.date.issued2021-12-21
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331218
dc.description.abstractACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent 'Long COVID'. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.
dc.description.sponsorshipThis research was funded in whole, or in part by: Wellcome Trust (WT107715/Z/15/Z, A.P.D., and J.J.M.); Wellcome Trust Programme in Metabolic and Cardiovascular Disease (203814/Z/16/A, T.L.W., D.N.), Wellcome Trust Major Award (208363/Z/17/Z) for Imaging Core (G.S.); British Heart Foundation (FS/17/61/33473 A.P.D., R.G.C.M; TG/18/4/33770, A.P.D., J.J.M.; FS/18/46/33663, S.S.). Cambridge Biomedical Research Centre Biomedical Resources Grant (University of Cambridge, Cardiovascular Theme, RG64226). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleDifferential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites.
dc.typeArticle
prism.publicationNameSci Rep
dc.identifier.doi10.17863/CAM.78663
dcterms.dateAccepted2021-12-02
rioxxterms.versionofrecord10.1038/s41598-021-03731-9
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.contributor.orcidSinha, Sanjay [0000-0001-5900-1209]
dc.contributor.orcidMaguire, Janet [0000-0002-9254-7040]
dc.contributor.orcidDavenport, Anthony [0000-0002-2096-3117]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (SP/15/7/31561)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idWellcome Trust (107715/Z/15/Z)
pubs.funder-project-idBritish Heart Foundation (TG/18/4/33770)
pubs.funder-project-idWellcome Trust (203814/Z/16/Z)
pubs.funder-project-idWellcome Trust (208363/Z/17/Z)
pubs.funder-project-idBritish Heart Foundation (BHF-FS/18/46/33663)
pubs.funder-project-idBritish Heart Foundation (FS/17/61/33473D)
cam.issuedOnline2021-12-21
cam.orpheus.successTue Feb 01 19:02:17 GMT 2022 - Embargo updated*
rioxxterms.freetoread.startdate2021-12-21


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