{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:29:06Z","timestamp":1781886546082,"version":"3.54.5"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["EMDR\/ SG\/ 9\/ 2023-2364"],"award-info":[{"award-number":["EMDR\/ SG\/ 9\/ 2023-2364"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University Grants Commission","award":["DEC18-319539"],"award-info":[{"award-number":["DEC18-319539"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,2,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Extracellular vesicles (EVs) emerged as critical contributors to the pathogenesis of vascular endothelial barrier dysfunction during the inflammatory response to infection. However, the contribution of circulating EVs to modifying endothelial function during dengue virus infection remains unclear. In this study, we showed that severe dengue patients\u2019 plasma-derived EV (SD-EV) were found to carry elevated levels of different protein cargos, e.g., immunoregulatory proteins (PD-L1, CD44). Further, we demonstrated that SD-EV induces PD-1 and CD44 expression on CD4\n              <jats:sup>+<\/jats:sup>\n              T cells. SD-EV-modulated CD4\n              <jats:sup>+<\/jats:sup>\n              T (SD-EV-CD4) cells released secretome delayed endothelial cell (EC) migration, arrested them in the G1 phase, and augmented the expression of PD-L1 and ICAM-1 expression on EC through the Notch signaling pathway. Blocking SD-EV and CD4\n              <jats:sup>+<\/jats:sup>\n              T-cell interaction through the PD-1\/PD-L1 pathway partially rescued the CD4\n              <jats:sup>+<\/jats:sup>\n              T cell\u2019s effect on EC but did not alter ICAM-1 expression on EC. We observed that the ICAM-1 expression on EC and hyaluronic acid (HA) release from EC was mediated by CD44, which was elevated on SD-EV-modulated CD4\n              <jats:sup>+<\/jats:sup>\n              T cells (SD-EV-CD4), indicating a permeability defect. Blocking of CD44 on SD-EV-CD4 significantly reduced ICAM-1 expression on EC. Further, depletion of specific cytokines, e.g., TNF-\u03b1 and not IFN-\u03b3 from the SD-EV-CD4 secretome, reduced ICAM-1 expression, decreased transendothelial electrical resistance, and induced apoptosis on EC significantly. Treatment with NF-kB inhibitor before secretome addition to EC reduced ICAM-1 expression on EC. In conclusion, we provided evidence that SD-EV-CD4 carrying PD-1 and CD44, when interacting with EC, significantly affected endothelial cell properties and may be significant in dengue-mediated endothelial dysfunction.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Extracellular vesicles (EVs) are small membrane vesicles secreted into biological fluids, including plasma from living cells, holding insights into pathological processes. Studying EVs under pathological conditions is extremely important as they play a selective role in intercellular communication and modulation of immune response under diverse pathological conditions. However, there is less clarity on how circulatory extracellular vesicles influence immune cells during dengue virus (DV) infection and impact pathogenesis. Our present study highlights the impact of severe dengue patients\u2019 plasma-derived EV (SD-EV) on CD4\n                <jats:sup>+<\/jats:sup>\n                T cells and together induce endothelial barrier dysfunction. We provided evidence that SD-EV induces PD-1 and CD44 on CD4\n                <jats:sup>+<\/jats:sup>\n                T cells and, when interacting with endothelial cells (EC), drives endothelial damage through direct interaction or secretome and may be significant in dengue-mediated endothelial dysfunction.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01861-24","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:00:59Z","timestamp":1735650059000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Induction of PD-1 and CD44 in CD4\n            <sup>+<\/sup>\n            T cells by circulatory extracellular vesicles from severe dengue patients drives endothelial damage via the NF-kB signaling pathway"],"prefix":"10.1128","volume":"99","author":[{"given":"Sharda","family":"Kumari","sequence":"first","affiliation":[{"name":"Laboratory of Virology, Regional Centre for Biotechnology, National Capital Region Biotechnology Science Cluster","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Biswas","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Regional Centre for Biotechnology, National Capital Region Biotechnology Science Cluster","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar Kanti","family":"Maiti","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Regional Centre for Biotechnology, National Capital Region Biotechnology Science Cluster","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaswati","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Tropical Medicine","place":["Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-1763","authenticated-orcid":true,"given":"Arup","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Regional Centre for Biotechnology, National Capital Region Biotechnology Science Cluster","place":["Faridabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12748"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2700.76835"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.10.019"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2012.11-0606"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005738"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006673"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10060326"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010065"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906467106"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00968-08"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107615"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02985-x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000002230"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00011-12"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041170"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy360"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15002"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2511-3"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44868-y"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01823-23"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12060623"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004424"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218159"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03030"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324270"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00250.2011"},{"key":"e_1_3_4_28_2","first-page":"1","volume-title":"Adhesion molecule","author":"Haydinger CD","year":"2023","unstructured":"Haydinger CD, Ashander LM, Chun A, Tan R, Smith JR. 2023. 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