{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:59:25Z","timestamp":1790780365607,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R56AI170226"],"award-info":[{"award-number":["1R56AI170226"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["UM1-AI164567"],"award-info":[{"award-number":["UM1-AI164567"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54-AI170792"],"award-info":[{"award-number":["U54-AI170792"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:p>\n                    The estrogen receptor (ER) is hypothesized to directly influence HIV transcription and latency but is also critical for immune signaling. However, the mechanisms of action of the ER in immune cells in the context of HIV are limited, and relevant to HIV cure strategies, the influence of latency reversal agents (LRAs) on the ER pathway are unknown. We evaluated (a) the effect of estrogen (E2) on the nuclear translocation of ER\u03b1 in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells; (b) the ability of Fulvestrant, a selective estrogen receptor degrader (SERD), and ARV-471, a potent, PROteolysis TArgeting Chimera (PROTAC) selective ER\u03b1 degrader to modulate ER\u03b1; and c) the effect of different classes of LRAs on ER\u03b1 signaling. In contrast to what has been demonstrated in oncology, E2 did not induce ER\u03b1 nuclear translocation in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Similarly, neither Fulvestrant nor ARV-471 induced degradation of ER\u03b1 in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. LRAs significantly downregulated ER\u03b1 gene and protein expression in both PBMCs and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Collectively, our results suggest that estrogen influences on HIV transcription are not likely a consequence of canonical nuclear ER\u03b1 mechanisms. The consequences of LRA downregulation of ER\u03b1, a protein important for immune signaling, warrant further investigation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198415","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:05:58Z","timestamp":1783706758000},"source":"Crossref","is-referenced-by-count":1,"title":["Effect of ligands and HIV latency-reversing agents on estrogen receptor \u03b1 in CD4+ T cells"],"prefix":"10.1172","volume":"11","author":[{"given":"Cristina","family":"Ceriani","sequence":"first","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Medicine, The University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Khetan","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Microbiology and Immunology, UNC at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Abeyta-Lopez","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Division of Translational Informatics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kena J.","family":"Lemu","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prachi","family":"Meher","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Allard","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Medicine, The University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine S.","family":"James","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Medicine, The University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7312-4616","authenticated-orcid":true,"given":"Anne-Marie W.","family":"Turner","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Medicine, The University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5714-0002","authenticated-orcid":true,"given":"David M.","family":"Margolis","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Medicine, The University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA."},{"name":"Department of Microbiology and Immunology, UNC at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancie M.","family":"Archin","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center, and"},{"name":"Department of Medicine, The University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","unstructured":"UNAIDS. 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