{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:38:35Z","timestamp":1792096715127,"version":"4.4.0"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["DST\/INSPIRE\/04\/2016\/000169"],"award-info":[{"award-number":["DST\/INSPIRE\/04\/2016\/000169"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dengue virus (DENV) infection disrupts host innate immune signaling at various checkpoints. Cellular levels and stability of intermediate signaling molecules are a crucial hijacking point for a successful viral pathogenesis. Stability and turnover of all the cellular proteins including intermediate signaling molecules are principally regulated by proteasomal degradation pathway. In this study, we show that how DENV infection and particularly DENV-NS1 can modulate the host extracellular vesicle (EV) cargo to manipulate the deubiquitination machinery of the human microglial cell (CHME3). We have performed EV harvesting, size analysis by nanoparticle tracking analysis, identification of cargo microRNA via quantitative PCR, microRNA target validation by overexpression, and knockdown via mimics and anti-miRs, immunoblotting, dual luciferase reporter assay, in vivo ubiquitination assay, chase assay, and promoter activity assay to reach the conclusion. In this study, we show that DENV-infected monocytes and DENV-NS1\u2013transfected cells release high amounts of EVs loaded with miR-148a. These EVs get internalized by human microglial cells, and miR-148a suppresses the ubiquitin-specific peptidase 33 (USP33) protein expression levels via binding to its 3\u2032 untranslated region. Reduced USP33 in turn decreases the stability of cellular ATF3 protein via deubiquitylation. ATF3 acts as a suppressor of major proinflammatory gene expression pathways of TNF-\u03b1, NF-\u03baB, and IFN-\u03b2. Our mechanistic model explains how DENV uses the EV pathway to transfer miR-148a for modulating USP33 and downstream ATF3 levels in human microglial cells and contributes in neuroinflammation within the CNS.<\/jats:p>","DOI":"10.4049\/jimmunol.2000411","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T22:00:14Z","timestamp":1598479214000},"page":"1787-1798","source":"Crossref","is-referenced-by-count":40,"title":["Dengue Virus Degrades USP33\u2013ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells"],"prefix":"10.1093","volume":"205","author":[{"given":"Ritu","family":"Mishra","sequence":"first","affiliation":[{"name":"Laboratory of Virology, National Institute of Immunology , New Delhi 110067 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-3114","authenticated-orcid":false,"given":"Anismrita","family":"Lahon","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Immunology , New Delhi 110067 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil C","family":"Banerjea","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Immunology , New Delhi 110067 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"issue":"12","key":"2025030417505085200_r1","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1038\/nrmicro2460","article-title":"Dengue: a continuing global threat","volume":"8","author":"Guzman","year":"2010","journal-title":"Nat. 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