{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:59:14Z","timestamp":1792180754996,"version":"4.4.0"},"reference-count":189,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Despite effective suppression of viral replication by antiretroviral therapy (ART), chronic HIV infection remains characterized by persistent low-level inflammation and progressive tissue damage, contributing to premature aging and an array of comorbidities including cardiovascular disease, HIV-associated neurocognitive disorders, liver disease, and fibrosis of multiple organs. Increased levels of transforming growth factor beta (TGF-\u03b2), characteristic of chronic HIV infection even in the context of ART, appear to be a common thread explaining these disparate comorbidities. As a pleiotropic cytokine with both immunosuppressive and pro-fibrotic properties, TGF-\u03b2 exerts complex and sometimes paradoxical effects on the HIV lifecycle and pathogenesis. This review explores the multifaceted roles of TGF-\u03b2 in HIV infection, with particular focus on three critical areas: immunosuppression, tissue fibrosis, and the regulation of viral latency. We discuss recent advancements in understanding the often-paradoxical role of TGF-\u03b2 on HIV replication and latency dynamics, and how its different effects contribute to multiple mechanisms underlying HIV persistence, from inhibited immune responses and enhanced viral latency to impaired immune reconstitution. A more comprehensive understanding of the mechanisms by which TGF-\u03b2 contributes to HIV persistence may illuminate novel therapeutic strategies targeting TGF-\u03b2 signaling pathways for improved HIV treatment and progression toward functional cure.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1738092","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:53:49Z","timestamp":1767768829000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Double, double toil and trouble: transforming growth factor beta (TGF-\u03b2) in HIV infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Jakob","family":"Harrison-Gleason","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla L.","family":"Yerlioglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel 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