{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:52:00Z","timestamp":1790718720566,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009820","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000}}],"reference-count":97,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"king\u2019s together rapid covid-19 call awards"},{"name":"king's together rapid covid-19 call awards"},{"name":"king's together rapid covid-19 call awards"},{"DOI":"10.13039\/100004440","name":"wellcome trust","doi-asserted-by":"publisher","award":["106223\/Z\/14\/Z"],"award-info":[{"award-number":["106223\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"huo family foundation award"},{"name":"huo family foundation award"},{"name":"huo family foundation award"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI150472"],"award-info":[{"award-number":["AI150472"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC\/UKRI","award":["MR\/N013700\/1"],"award-info":[{"award-number":["MR\/N013700\/1"]}]},{"name":"mrc-kcl doctoral training partnership in biomedical sciences","award":["MR\/N013700\/1"],"award-info":[{"award-number":["MR\/N013700\/1"]}]},{"name":"mrc-kcl doctoral training partnership in biomedical sciences","award":["MR\/N013700\/1"],"award-info":[{"award-number":["MR\/N013700\/1"]}]},{"name":"Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with the vacuolar ATPase, and promotes endo-lysosomal vesicle acidification and lysosomal protease activity. Here, we used ectopic expression and gene knockout to demonstrate that NCOA7 inhibits infection by SARS-CoV-2 as well as by lentivirus particles pseudotyped with SARS-CoV-2 Spike in lung epithelial cells. Infection with the highly pathogenic, SARS-CoV-1 and MERS-CoV, or seasonal, HCoV-229E and HCoV-NL63, coronavirus Spike-pseudotyped viruses was also inhibited by NCOA7. Importantly, either overexpression of TMPRSS2, which promotes plasma membrane fusion versus endosomal fusion of SARS-CoV-2, or removal of Spike\u2019s polybasic furin cleavage site rendered SARS-CoV-2 less sensitive to NCOA7 restriction. Collectively, our data indicate that furin cleavage sensitizes SARS-CoV-2 Spike to the antiviral consequences of endosomal acidification by NCOA7, and suggest that the acquisition of furin cleavage may have favoured the co-option of cell surface TMPRSS proteases as a strategy to evade the suppressive effects of IFN-induced endo-lysosomal dysregulation on virus infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009820","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T13:35:05Z","timestamp":1637588105000},"page":"e1009820","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["TMPRSS2 promotes SARS-CoV-2 evasion from NCOA7-mediated restriction"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1128-0266","authenticated-orcid":true,"given":"Hataf","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1936-6638","authenticated-orcid":true,"given":"Helena","family":"Winstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-8033","authenticated-orcid":true,"given":"Jose M.","family":"Jimenez-Guarde\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-1725","authenticated-orcid":true,"given":"Katie J.","family":"Doores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-1108","authenticated-orcid":true,"given":"Caroline","family":"Goujon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-8795","authenticated-orcid":true,"given":"David A.","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9495-4056","authenticated-orcid":true,"given":"Suzannah J.","family":"Rihn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7007-4070","authenticated-orcid":true,"given":"Massimo","family":"Palmarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J. D.","family":"Neil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7699-2064","authenticated-orcid":true,"given":"Michael H.","family":"Malim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ppat.1009820.ref001","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/bs.aivir.2018.01.001","article-title":"Hosts and Sources of Endemic Human Coronaviruses.","volume":"100","author":"VM Corman","year":"2018","journal-title":"Adv Virus Res"},{"key":"ppat.1009820.ref002","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"P V\u2019kovski","year":"2021","journal-title":"Nat Rev 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