{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:31:47Z","timestamp":1791599507074,"version":"4.3.4"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"General Research Fund","award":["17119122"],"award-info":[{"award-number":["17119122"]}]},{"name":"Collaborative Research Fund","award":["C7103-22G"],"award-info":[{"award-number":["C7103-22G"]}]},{"name":"Theme-Based Research Fund","award":["T11-706\/18-N"],"award-info":[{"award-number":["T11-706\/18-N"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,5,27]]},"abstract":"<jats:p>\n                    A major challenge for HIV type 1 (HIV-1) cure is the presence of viral latent reservoirs. The \u201cShock &amp; Kill\u201d strategy involves the combined use of latency reversal agents (LRA) and antiretroviral treatment (ART) to reactivate HIV-1 latent reservoirs, followed by elimination of infected cells. However, current LRAs are insufficient in fully reactivating the latent reservoirs. Therefore, investigation on novel HIV-1 latency regulators will be crucial to the success of HIV-1 cure research. Here, we identify bromodomain-containing protein 9 (BRD9) as an HIV-1 latency regulator. BRD9 inhibition induces HIV-1 latency reactivation in T cell lines, human resting memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and PBMCs derived from people living with HIV-1 (PWH) on ART. BRD9 inhibition, gene depletion, and protein degradation consistently reactivate HIV-1 latency. Moreover, BRD9 inhibition synergizes with BRD4 inhibition in inducing HIV-1 production. Mechanistically, BRD9 binds to HIV-1 LTR promoter and competes with HIV-1 Tat protein for binding to the HIV-1 genome. Additionally, our integrated CUT&amp;RUN DNA sequencing, transcriptomics, and pharmacological analysis revealed downstream host targets of BRD9, including ATAD2 and MTHFD2, that modulate HIV-1 latency.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2418467122","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T11:10:46Z","timestamp":1747912246000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["BRD9 functions as an HIV-1 latency regulatory factor"],"prefix":"10.1073","volume":"122","author":[{"given":"Tsz-Yat","family":"Luk","sequence":"first","affiliation":[{"name":"AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]},{"name":"Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lok-Yan","family":"Yim","sequence":"additional","affiliation":[{"name":"AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]},{"name":"Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]},{"name":"Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special 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and Technology Park","place":["Hong Kong Special Administrative Region of China"]},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]},{"name":"Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital","place":["Shenzhen, Guangdong 518053, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper Fuk-Woo","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Hong Kong Special Administrative Region of China"]},{"name":"Center for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park","place":["Hong Kong Special Administrative Region of China"]},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong 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