{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:03:45Z","timestamp":1790435025001,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE028129"],"award-info":[{"award-number":["R01DE028129"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA232887"],"award-info":[{"award-number":["R01CA232887"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Mother-to-child transmission (MTCT) of HIV-1 may occur during pregnancy, labor, and breastfeeding; however, the molecular mechanism of MTCT of virus remains poorly understood. Infant tonsil mucosal epithelium may sequester HIV-1, serving as a transient reservoir, and may play a critical role in MTCT. Innate immune proteins human beta-defensins 2 (hBD-2) and -3 may inactivate intravesicular virions. To establish delivery of hBD-2 and -3 into vesicles containing HIV-1, we tagged hBDs with the protein transduction domain (PTD) of HIV-1 Tat, which facilitates an efficient translocation of proteins across cell membranes. Our new findings showed that hBD-2 and -3 proteins tagged with PTD efficiently penetrated polarized tonsil epithelial cells by endocytosis and direct penetration. PTD-initiated internalization of hBD-2 and -3 proteins into epithelial cells led to their subsequent penetration of multivesicular bodies (MVB) and vacuoles containing HIV-1. Furthermore, PTD played a role in the fusion of vesicles containing HIV-1 with lysosomes, where virus was inactivated. PTD-initiated internalization of hBD-2 and -3 proteins into ex vivo tonsil tissue explants reduced the spread of virus from epithelial cells to CD4+ T lymphocytes, CD68+ macrophages, and CD1c+ dendritic cells, suggesting that this approach may serve as an antiviral strategy for inactivating intraepithelial HIV-1 and reducing viral MTCT.<\/jats:p>","DOI":"10.3390\/v13102043","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T21:45:32Z","timestamp":1633988732000},"page":"2043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inactivation of HIV-1 in Polarized Infant Tonsil Epithelial Cells by Human Beta-Defensins 2 and 3 Tagged with the Protein Transduction Domain of HIV-1 Tat"],"prefix":"10.3390","volume":"13","author":[{"given":"Rossana","family":"Herrera","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California\u2013San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Rosbe","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of California\u2013San Francisco, San Francisco, CA 94115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3743-4334","authenticated-orcid":false,"given":"Sharof M.","family":"Tugizov","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California\u2013San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.virol.2010.10.004","article-title":"HIV is inactivated after transepithelial migration via adult oral epithelial cells but not fetal epithelial cells","volume":"409","author":"Tugizov","year":"2011","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1128\/JVI.06578-11","article-title":"Differential Transmission of HIV Traversing Fetal Oral\/Intestinal Epithelia and Adult Oral Epithelia","volume":"86","author":"Tugizov","year":"2011","journal-title":"J. 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