{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T07:09:20Z","timestamp":1773644960147,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01575 , PI24\/00636, JR23\/00044"],"award-info":[{"award-number":["PI22\/01575 , PI24\/00636, JR23\/00044"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2021-124226OB-I00"],"award-info":[{"award-number":["PID2021-124226OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2021 SGR 00452"],"award-info":[{"award-number":["2021 SGR 00452"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The persistence of latent HIV-1 reservoirs remains a major barrier to achieving a cure for HIV. While latency-reversing agents (LRAs) have been extensively studied, latency-promoting agents (LPAs) offer a complementary strategy to silence viral transcription and prevent immune activation. Here, we propose that modulation of IRF7-driven transcription may represent a novel approach to control HIV-1 latency, by characterizing the role of the Janus kinase 2 inhibitor (JAK2i) pacritinib as a novel latency-promoting agent (LPA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The impact of JAK2i on HIV-1 reactivation, immune activation, and IRF7 expression were evaluated in lymphoid and myeloid HIV-1 latency models, as well as\n                      <jats:italic>ex vivo<\/jats:italic>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells from ART-suppressed individuals. IRF7 modulation was assessed by qRT-PCR and immunoblotting, and its functional role confirmed through LTR transactivation assays and IRF7 overexpression. Co-immunoprecipitation was used to detect IRF7\u2013Tat interaction. Whole transcriptomic profiling with pathway analysis were performed to identify the molecular signatures associated with JAK2i treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pacritinib effectively suppressed HIV-1 latency reversal induced by LRAs without triggering immune activation. Mechanistically, pacritinib downregulated IRF7 expression at both transcript and protein levels, correlating with reduced HIV-1 transcription. Overexpression of IRF7 restored LTR transactivation, confirming its central role in HIV-1 transcription and latency. Co-immunoprecipitation assays revealed a direct interaction between IRF7 and the viral transactivator Tat. Furthermore, pacritinib selectively inhibited multiply spliced HIV-1 transcripts, suggesting a blockade at late transcriptional stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pacritinib acts as a potent LPA by silencing HIV-1 transcription through IRF7 downregulation, supporting a promising \u201cblock and lock\u201d strategy for functional cure approaches. Targeting IRF7 may enable durable suppression of the viral reservoir without immune activation, supporting the development of \u201cblock and lock\u201d therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1735192","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T06:36:40Z","timestamp":1773643000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of IRF7-driven transcription as a strategy to control HIV-1 latency"],"prefix":"10.3389","volume":"17","author":[{"given":"Ifeanyi Jude","family":"Ezeonwumelu","sequence":"first","affiliation":[{"name":"IrsiCaixa","place":["Badalona, Spain"]},{"name":"Health Research Institute Germans Trias i Pujol (IGTP), Hospital Universitari Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona","place":["Badalona, 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