{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T15:37:13Z","timestamp":1775576233762,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08829"],"award-info":[{"award-number":["20K08829"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Virus\u2013host cell interactions in rubella virus (RuV) are of great interest in current research in the field, as their mechanism is not yet well understood. By hypothesizing that the epithelial-to-mesenchymal transition (EMT) may play a role in RuV infection, this study aimed to investigate the influence of TGF-\u03b21-induced EMT of human lung epithelial A549 cells on the infectivity of RuV. A549 cells were cultured and treated with TGF-\u03b21 for 1 to 2 days prior to virus infection (with a clinical strain). Viral infectivity was determined by flow cytometry analysis of cells harvested at 24 and 48 h post-infection (hpi) and by titration of supernatants collected at 48 hpi. The results showed that the percentages of the TGF-\u03b21-treated A549 cells that were positive for RuV were at least twofold higher than those of the control, and the viral progeny titers in the supernatants collected at 48 hpi were significantly higher in the treatment group than in the control group. In addition, the virus binding assay showed a strong increase (more than threefold) in the percentages of RuV-positive cells, as determined by flow cytometry analysis and further confirmed by real-time PCR. Such an enhancement effect on RuV infectivity was abolished using LY364947 or SB431542, inhibitors of the TGF-\u03b2\/Smad signaling pathway. The findings suggest that the TGF-\u03b21-induced EMT-like process enhances RuV binding and infection in A549 cells via the Smad pathway. Further studies are necessary to identify possible proteins that facilitate viral binding and entry into treated cells.<\/jats:p>","DOI":"10.3390\/microorganisms9030662","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T14:08:16Z","timestamp":1616508496000},"page":"662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Epithelial-to-Mesenchymal Transition-Like Process Induced by TGF-\u03b21 Enhances Rubella Virus Binding and Infection in A549 Cells via the Smad Pathway"],"prefix":"10.3390","volume":"9","author":[{"given":"Ngan Thi Kim","family":"Pham","sequence":"first","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5610-1570","authenticated-orcid":false,"given":"Quang Duy","family":"Trinh","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-0243","authenticated-orcid":false,"given":"Kazuhide","family":"Takada","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chika","family":"Takano","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2206-282X","authenticated-orcid":false,"given":"Shoko","family":"Okitsu","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ushijima","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-0315","authenticated-orcid":false,"given":"Shihoko","family":"Komine-Aizawa","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-1443","authenticated-orcid":false,"given":"Satoshi","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"ref_1","unstructured":"Chen, R., Mukhopadhyay, S., Merits, A., Bolling, B., Nasar, F., Coffey, L., Powers, A., Weaver, S., Smith, D., and Simmonds, P. 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