{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:57Z","timestamp":1785428097706,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CCTS","award":["TR003169"],"award-info":[{"award-number":["TR003169"]}]},{"DOI":"10.13039\/100010301","name":"Oral and Maxillofacial Surgery Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010301","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05kyj3g94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"ACCEL"},{"DOI":"10.13039\/100013527","name":"Dental Trade Alliance Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013527","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["R01DE032364"],"award-info":[{"award-number":["R01DE032364"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01DE032364"],"award-info":[{"award-number":["R01DE032364"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health"},{"DOI":"10.13039\/100007313","name":"University of Texas MD Anderson Cancer Center","doi-asserted-by":"crossref","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}],"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Salivary gland infection by SARS-CoV-2 requires viral entry via routes and mechanisms that remain unresolved. This study examined the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in salivary tissues and basal cell-derived human salivary progenitor cells (hS\/PCs), an unstudied potential entry point for SARS-CoV-2. Multiple detection modalities, including immunocytochemistry, Western blotting, flow cytometry and RT-PCR, demonstrated a consistent lack of ACE2 protein and transcript in both tissue specimens and primary salivary epithelial cells. Antigen retrieval at pH 9 was determined to be optimal for immunodetection protocols, yet ACE2 remained undetectable. Small intestine tissue served as a positive control, confirming the validity of the methods and reagents we used. Considering there can be other receptors for SARS-CoV-2, flow cytometric analyses demonstrated that recombinant SARS-CoV-2 spike protein failed to bind to salivary epithelial cells, in contrast to HEK293 cells engineered to overexpress ACE2, which showed robust spike binding. Additional studies showed that patient-derived salivary cells, negative for ACE2, are not infected by the SARS-CoV-2 pseudovirus, while ACE2-positive cells are readily infected. These findings strongly support our conclusion that salivary cells do not serve as major targets for SARS-CoV-2 infection via ACE2, spike protein, or an alternate receptor. Thus, salivary cells are unlikely major targets for SARS-CoV-2 infection, either through direct exposure to viral particles in ductal fluids or via access to basal cells across the basement membrane.<\/jats:p>","DOI":"10.3390\/biology15100778","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Spike-Dependent and ACE2-Independent SARS-CoV-2 Interactions with Salivary Epithelial Cells in the Absence of ACE2"],"prefix":"10.3390","volume":"15","author":[{"given":"Caitlynn M. L.","family":"Barrows","sequence":"first","affiliation":[{"name":"Katz Department of Oral and Maxillofacial Surgery, UTHealth Houston School of Dentistry, Houston, TX 77054, USA"},{"name":"Department of Diagnostic and Biomedical Sciences, UTHealth Houston School of Dentistry, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-9781","authenticated-orcid":false,"given":"Thaise C.","family":"Geremias","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, UTHealth Houston School of Dentistry, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-7083","authenticated-orcid":false,"given":"Simon","family":"Young","sequence":"additional","affiliation":[{"name":"Katz Department of Oral and Maxillofacial Surgery, UTHealth Houston School of Dentistry, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-3088","authenticated-orcid":false,"given":"Mary C.","family":"Farach-Carson","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, UTHealth Houston School of Dentistry, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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