{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T08:13:55Z","timestamp":1778141635946,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,4]]},"group-title":"Microbiology","reference-count":88,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Belgian Fund for Scientific Research"},{"name":"Internationale Brachet Stiftung"},{"name":"the French INSERM agency \u201cANRS\/Maladies infectieuses \u00e9mergentes\u201d"},{"name":"the Universit\u00e9 libre de Bruxelles (ULB - Action de Recherche Concert\u00e9e"},{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The \u201cAmis des Instituts Pasteur \u00e0 Bruxelles\u201d, asbl"},{"name":"the US National Institutes of Health (NIH)","award":["MDC grant 1UM1AI164562"],"award-info":[{"award-number":["MDC grant 1UM1AI164562"]}]},{"DOI":"10.13039\/501100000024","name":"the Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["CIHR project grant PTJ-195736"],"award-info":[{"award-number":["CIHR project grant PTJ-195736"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the BREACH Foundation"},{"name":"the Canadian HIV Cure Enterprise Team Grant (CanCURE2.0 and 3.0) funded by the Canadian Institutes of Health Research","award":["#HB2-164064; BR4 197730"],"award-info":[{"award-number":["#HB2-164064; BR4 197730"]}]},{"DOI":"10.13039\/501100000024","name":"the Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["CIHR project grants (PJT #153052; PJT #178127; PJ4-192194; PTJ-195736)"],"award-info":[{"award-number":["CIHR project grants (PJT #153052; PJT #178127; PJ4-192194; PTJ-195736)"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Fondation du CHUM"},{"name":"the Fonds de recherche Qu\u00e9bec Sant\u00e9 (FRQS) HIV\/AIDS and Infectious Diseases Network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,4]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Despite antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) persists in latently-infected cells through epigenetic and transcriptional mechanisms. Latency-reversing agents have failed clinically, partly due to incomplete understanding of HIV-1 latency reversal. Here, using DNA-affinity capture and mass spectrometry on the HIV-1 5\u2019 long terminal repeat (5\u2019LTR) enhancer-core promoter, we identify KLF16 (Kr\u00fcppel-like Factor 16) as a novel regulator of HIV-1 gene expression. KLF16 binds to the HIV-1 5\u2019LTR\n                  <jats:italic>in vivo<\/jats:italic>\n                  at Sp1 binding sites, and KLF16 depletion reactivates latent HIV-1 in T-lymphoid and monocytic cell models. Mechanistically, KLF16 represses HIV-1 transcription by competing with Sp1 for promoter binding and by recruiting the Sin3A\/HDAC1 and HP1\u03b1\/Suv39H1 repressive epigenetic complexes. KLF16 is also upregulated in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells from ART-treated people with HIV-1 upon T-cell activation. Additionally, All-Trans retinoic acid (ATRA) reactivates latent HIV-1 in myeloid cells, partly by downregulating KLF16. These findings establish KLF16 as a novel transcriptional repressor of HIV-1, identifying it as a potential promising therapeutic target for cure strategies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"722432v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.02.722432","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:45:24Z","timestamp":1777952724000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of the cellular transcription factor KLF16 as a novel repressive epigenetic repressor of HIV-1 transcription"],"prefix":"10.64898","author":[{"given":"Marion","family":"Santangelo","sequence":"first","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Bendoumou","sequence":"additional","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Dutilleul","sequence":"additional","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumia","family":"Khalfi","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie et immunologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de recherche du centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CR-CHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Plant","sequence":"additional","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christ Dominique","family":"Ngassaki-yoka","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie et immunologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de recherche du centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CR-CHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Pilosio","sequence":"additional","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Vanhulle","sequence":"additional","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Dias","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie et immunologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de recherche du centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CR-CHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Marray","sequence":"additional","affiliation":[{"name":"Service of Molecular Virology, Department of Molecular Biology (DBM), Universit\u00e9 libre de Bruxelles (ULB), Gosselies 6041, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Fattaccioli","sequence":"additional","affiliation":[{"name":"Research Unit in Cell Biology (URBC), Namur Research Institute for Life Sciences (Narilis), University of Namur (UNamur), Namur 5000, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Dieu","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Platform (MaSUN), University of Namur (UNamur), Namur 5000, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"Routy","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health 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