{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:50:27Z","timestamp":1789181427732,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013332","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"The Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/I\/18\/2\/504006"],"award-info":[{"award-number":["IA\/I\/18\/2\/504006"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["#5753"],"award-info":[{"award-number":["#5753"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012117","name":"Lady Tata Memorial Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["EM\/dev\/\/CAR\/-2024-01-0113\/F2\/2024"],"award-info":[{"award-number":["EM\/dev\/\/CAR\/-2024-01-0113\/F2\/2024"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anusandhan National Research Foundation","award":["CRG\/2023\/000720"],"award-info":[{"award-number":["CRG\/2023\/000720"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Circular RNA (circRNA) expression is widespread in immune cells infected by HIV-1, but the crosstalk between circRNA expression and various cellular signaling pathways remains elusive. Here, we report that HIV-1 Vpr can induce the production of TGF-\u03b2 during infection, which we linked to the upregulation of ciTRAN, a proviral circRNA encoded by <jats:italic>SMARCA5<\/jats:italic>. Consistent with this finding, we observed that the essential intracellular TGF-\u03b2 receptor signaling component SMAD2\/3 was recruited to the <jats:italic>SMARCA5<\/jats:italic> promoter in a Vpr-dependent manner. <jats:italic>SMARCA5<\/jats:italic> promoter analysis and functional assays further revealed that SAMD2\/3 binding motif in the <jats:italic>SMARCA5<\/jats:italic> promoter is crucial for ciTRAN upregulation. Notably, in response to treatment with DNA-damaging agents or the exogenous addition of recombinant TGF-\u03b2, the TGF-SMAD axis upregulated the expression of ciTRAN as well as the parental <jats:italic>SMARCA5<\/jats:italic> mRNA. Regardless, the QKI protein was necessary for ciTRAN biogenesis. Finally, pharmacological targeting or genetic ablation of <jats:italic>TGFBR1<\/jats:italic> can reduce the ability of Vpr to promote the expression of ciTRAN and viral genes. These results highlight the TGF-\u03b2-mediated regulation of ciTRAN expression which may play a role in modulating HIV-1 replication.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013332","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T17:52:03Z","timestamp":1752083523000},"page":"e1013332","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["HIV-1 Vpr orchestrates ciTRAN upregulation through TGF-\u03b2 induction"],"prefix":"10.1371","volume":"21","author":[{"given":"Aditi","family":"Choudhary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katyayani","family":"Mallick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishikesh","family":"Dalavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-5180","authenticated-orcid":true,"given":"Ajit","family":"Chande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"issue":"2","key":"ppat.1013332.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0030733","article-title":"Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types","volume":"7","author":"J Salzman","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"ppat.1013332.ref002","article-title":"Circular RNA is expressed across the eukaryotic tree of life","volume":"9","author":"PL Wang","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1013332.ref003","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1261\/rna.035667.112","article-title":"Circular RNAs are abundant, conserved, and associated with ALU repeats","volume":"19","author":"WR Jeck","year":"2013","journal-title":"RNA"},{"issue":"1","key":"ppat.1013332.ref004","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cell.2014.09.001","article-title":"Complementary sequence-mediated exon circularization","volume":"159","author":"X-O Zhang","year":"2014","journal-title":"Cell"},{"issue":"1","key":"ppat.1013332.ref005","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.celrep.2014.12.002","article-title":"Exon circularization requires canonical splice signals","volume":"10","author":"S Starke","year":"2015","journal-title":"Cell Rep"},{"issue":"6","key":"ppat.1013332.ref006","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/cr.2016.42","article-title":"CircRNA-derived pseudogenes","volume":"26","author":"R Dong","year":"2016","journal-title":"Cell Res"},{"key":"ppat.1013332.ref007","first-page":"1829","volume-title":"Circular RNAs: Diversity of form and function. 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