{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:04:45Z","timestamp":1790687085079,"version":"4.1.0"},"reference-count":41,"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\/501100013238","name":"Faculty of Medicine Siriraj Hospital, Mahidol University","doi-asserted-by":"publisher","award":["60\u2013009, 61\u2013050, 63\u2013068"],"award-info":[{"award-number":["60\u2013009, 61\u2013050, 63\u2013068"]}],"id":[{"id":"10.13039\/501100013238","id-type":"DOI","asserted-by":"publisher"}]},{"name":"a Target Research Grant from the National Research Council of Thailand","award":["60\u2013009, 61\u2013050, 63\u2013068"],"award-info":[{"award-number":["60\u2013009, 61\u2013050, 63\u2013068"]}]},{"name":"a grant from the Thailand Research Fund","award":["IRG 5980006"],"award-info":[{"award-number":["IRG 5980006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>It has been hypothesized that the host, viral factors, and secreted cytokines (especially TNF-\u03b1) play roles in the pathogenesis of secondary dengue infections. Mass spectrometry-based proteomic screening of cytoskeleton fractions isolated from human endothelial (EA.hy926) cells upon dengue virus (DENV) infection and TNF-\u03b1 treatment identified 450 differentially altered proteins. Among them, decreased levels of moesin, actin stress fiber rearrangements, and dot-like formations of vinculin were observed with western blot analyses and\/or immunofluorescence staining (IFA). In vitro vascular permeability assays using EA.hy926 cells, seeded on collagen-coated transwell inserts, showed low levels of transendothelial electrical resistance in treated cells. The synergistic effects of DENV infection and TNF-\u03b1 treatment caused cellular permeability changes in EA.hy926 cells, which coincided with decreasing moesin levels and the production of abnormal organizations of actin stress fibers and vinculin. Functional studies demonstrated moesin overexpression restored transendothelial permeability in DENV\/TNF-\u03b1-treated EA.hy926 cells. The present study improves the understanding of the disruption mechanisms of cytoskeleton proteins in enhancing vascular permeability during DENV infection and TNF-\u03b1 treatment. The study also suggests that these disruption mechanisms are major factors contributing to vascular leakage in severe dengue patients.<\/jats:p>","DOI":"10.3390\/v13102042","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T21:45:32Z","timestamp":1633988732000},"page":"2042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Altered Moesin and Actin Cytoskeleton Protein Rearrangements Affect Transendothelial Permeability in Human Endothelial Cells upon Dengue Virus Infection and TNF-\u03b1 Treatment"],"prefix":"10.3390","volume":"13","author":[{"given":"Aroonroong","family":"Suttitheptumrong","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanaporn","family":"Mahutchariyakul","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nantapon","family":"Rawarak","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1154-6485","authenticated-orcid":false,"given":"Onrapak","family":"Reamtong","sequence":"additional","affiliation":[{"name":"Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kobporn","family":"Boonnak","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-8703","authenticated-orcid":false,"given":"Sa-nga","family":"Pattanakitsakul","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0140-6736(06)69006-5","article-title":"The WHO dengue classification and case definitions: Time for a reassessment","volume":"368","author":"Deen","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.1999.9656","article-title":"Immunopathogenesis of Dengue hemorrhagic fever","volume":"257","author":"Rothman","year":"1999","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.4049\/jimmunol.175.4.2676","article-title":"Altered cytokine responses of dengue-specific CD4+ T cells to heterologous serotypes","volume":"175","author":"Mangada","year":"2005","journal-title":"J. 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