{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:02:00Z","timestamp":1791511320043,"version":"4.3.4"},"posted":{"date-parts":[[2026,4,9]]},"group-title":"Microbiology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R21 AI167709-01A1"],"award-info":[{"award-number":["R21 AI167709-01A1"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI186609"],"award-info":[{"award-number":["R01AI186609"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21MH128034"],"award-info":[{"award-number":["R21MH128034"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01MH136852"],"award-info":[{"award-number":["R01MH136852"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Collaboratory of AIDS Researchers for Eradication","award":["UM1AI164567"],"award-info":[{"award-number":["UM1AI164567"]}]},{"name":"Collaborative Development Program at B-HIVE","award":["U54AI170855"],"award-info":[{"award-number":["U54AI170855"]}]},{"name":"NIH","award":["R35GM145351"],"award-info":[{"award-number":["R35GM145351"]}]},{"name":"NIH","award":["R01CA291968"],"award-info":[{"award-number":["R01CA291968"]}]},{"name":"NIH","award":["R01CA260666"],"award-info":[{"award-number":["R01CA260666"]}]},{"name":"Translational Virology Core at the San Diego Center for AIDS Research","award":["P30AI036214"],"award-info":[{"award-number":["P30AI036214"]}]},{"name":"The James B. 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Disruption of the ENL\u2013USP7 complex using selective PROTACs reactivates latent HIV in cell line models, as well as in resting CD4\u207a T cells and microglia isolated from people with HIV on antiretroviral therapy. These findings uncover a critical ENL\u2013USP7\u2013BRD4 axis that enforces HIV-1 latency and highlight USP7 as a potential target for latency-reversing strategies.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>ENL, a YEATS domain-containing crotonylation reader, acts as a suppressor rather than an activator of HIV-1 transcription.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>ENL recruits USP7 to stabilize BRD4 and enforce viral latency.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Disruption of the ENL\u2013USP7\u2013BRD4 axis reactivates latent HIV in T cells and microglia.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Targeting USP7 or ENL reveals a therapeutic vulnerability in HIV reservoirs.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.08.717209","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:25:15Z","timestamp":1775802315000},"source":"Crossref","is-referenced-by-count":3,"title":["The ENL\u2013USP7 Complex Regulates HIV Latency Through BRD4 Stabilization"],"prefix":"10.64898","author":[{"given":"Waqas","family":"Ahmed","sequence":"first","affiliation":[{"name":"UNC HIV Cure Center and Institute of Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Li","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center and Institute of Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciniso S.","family":"Shabangu","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center and Institute of Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Chen","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center and Institute of Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikesh","family":"Kutwal","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center and Institute of Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kirchherr","sequence":"additional","affiliation":[{"name":"UNC HIV Cure Center and Institute of Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshe R.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Texas A&M University, College Station, TX, 2007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcheng","family":"Song","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixiu","family":"Luo","sequence":"additional","affiliation":[{"name":"Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science, and Neuroscience, The Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Umit","family":"Kaniskan","sequence":"additional","affiliation":[{"name":"Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science, and Neuroscience, The Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Jin","sequence":"additional","affiliation":[{"name":"Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science, and Neuroscience, The Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gianella","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California at San Diego, La Jolla, CA, 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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