{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:09:11Z","timestamp":1740146951302,"version":"3.37.3"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004375","name":"Tel Aviv University","doi-asserted-by":"publisher","award":["100"],"award-info":[{"award-number":["100"]}],"id":[{"id":"10.13039\/501100004375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant\/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2\/furin membranous\/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal\/middle\/upper), on a 5-tier scale (0, 1\u2014weak, 1.5 \u2013weak-to-moderate, 2\u2014moderate, 3\u2014strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at p&lt;0.05.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>All oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Oral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-\u00e0-vis a comprehensive analysis of the literature.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0300269","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T17:47:08Z","timestamp":1710524828000},"page":"e0300269","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin"],"prefix":"10.1371","volume":"19","author":[{"given":"Osnat","family":"Grinstein-Koren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Lusthaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilla","family":"Tabibian-Keissar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilana","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amos","family":"Buchner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron","family":"Ilatov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-2333","authenticated-orcid":true,"given":"Marilena","family":"Vered","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayelet","family":"Zlotogorski-Hurvitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"issue":"7","key":"pone.0300269.ref001","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.3390\/genes12071061","article-title":"Correlates of SARS-CoV-2 variants on deaths, case incidence and case fatality ratio among the continents for the period of 1 December 2020 to 15 March 2021.","volume":"12","author":"W J Al-Awaida","year":"2021","journal-title":"Genes (Basel)."},{"issue":"7798","key":"pone.0300269.ref002","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"F Wu","year":"2020","journal-title":"Nature"},{"issue":"6","key":"pone.0300269.ref003","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.arcmed.2020.05.012","article-title":"Structural proteins in Severe Acute Respiratory Syndrome Coronavirus-2","volume":"51","author":"S Satarker","year":"2020","journal-title":"Arch Med Res"},{"issue":"3","key":"pone.0300269.ref004","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 Microbiol"},{"issue":"2","key":"pone.0300269.ref005","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3164\/jcbn.21-172","article-title":"Association of alcohol intake and female gender with high expression of TMPRSS2 in tongue as potential risk for SARS-CoV-2 infection","volume":"71","author":"K Sato","year":"2022","journal-title":"J Clin Biochem Nutr"},{"issue":"8","key":"pone.0300269.ref006","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1080\/07391102.2020.1754293","article-title":"A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin","volume":"39","author":"A Hasan","year":"2021","journal-title":"J Biomol Struct Dyn"},{"issue":"6965","key":"pone.0300269.ref007","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"W Li","year":"2003","journal-title":"Nature"},{"issue":"10","key":"pone.0300269.ref008","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/JPER.21-0277","article-title":"The \u201coral\u201d history of COVID-19: Primary infection, salivary transmission, and post-acute implications. 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