{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:16:32Z","timestamp":1793880992260,"version":"4.7.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371765"],"award-info":[{"award-number":["82371765"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071853"],"award-info":[{"award-number":["82071853"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Cholesterol 25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), has been implicated in broad-spectrum antiviral immunity. Here, we identify CH25H as a potent suppressor of hepatitis B virus (HBV) replication that significantly outperforms IFN-\u03b1 in reducing HBV DNA, pregenomic RNA (pgRNA), HBsAg, and HBeAg, without inducing cytotoxicity. However, CH25H is weakly expressed in hepatocytes and only modestly induced by type I interferon. We found that CH25H expression is tightly controlled by microRNAs, especially miR-7705, which is induced by IFN-\u03b1 in a STAT1-dependent manner. miR-7705 directly targets the 3\u2032UTR of CH25H, suppressing its expression and enhancing HBV replication. Knockdown of miR-7705 restores CH25H levels, enhances IFN-induced antiviral responses, and suppresses HBV replication in both transient transfection and infection models. Mechanistically, miR-7705 overexpression nullifies CH25H-mediated suppression of HBV, whereas this effect is abolished in CH25H-knockout cells, confirming the specificity of the miR-7705\u2013CH25H axis. Furthermore, we demonstrate that this regulatory axis also governs CH25H-mediated restriction of RNA viruses, including EV71 and CVB3, suggesting its broad antiviral relevance. Importantly, antagonizing miR-7705 enhances the efficacy of IFN-based therapy against both DNA and RNA viruses. These findings reveal miR-7705 as a negative regulator of CH25H and position the miR-7705\u2013CH25H axis as a promising target to improve antiviral immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This study highlights the critical role of miR-7705 in regulating the antiviral effects of interferon (IFN) therapy, particularly in the context of chronic HBV infection. By identifying miR-7705 as a key modulator of CH25H, a protein essential for controlling HBV replication, our research provides new insights into the mechanisms that limit the effectiveness of IFN treatment. Targeting miR-7705 could improve the efficacy of IFN-based therapies, offering a potential strategy to better manage HBV and other viral infections. This research paves the way for developing adjunctive treatments that enhance the body's natural antiviral responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01198-25","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T13:05:59Z","timestamp":1757509559000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Interferon-induced miR-7705 modulates the anti-virus activity of cholesterol 25-hydroxylase"],"prefix":"10.1128","volume":"99","author":[{"given":"Le","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034haf133","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, Institute of Translational Medicine, The First Hospital of Jilin University","place":["Changchun, 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