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While ALV-J evades innate immunity to sustain infection, the mechanisms remain unclear. Here, we show that ALV-J upregulates microRNA-155 (miR-155) to suppress type I interferon (IFN-I) responses, facilitating viral replication. Mechanistically, the ALV-J p27 protein reduced DEAD-box helicase 3X (DDX3X) promoter activity, repressing its expression and promoting MIR155 host gene (MIR155HG) processing into mature miR-155. miR-155 directly targets the tumor necrosis factor receptor-associated factor 3 (TRAF3) and the signal transducer and activator of transcription 1 (STAT1), both of which are key regulators of IFN-I response. Silencing TRAF3 or STAT1 rescues ALV-J replication suppressed by miR-155 inhibition. These findings reveal a novel miRNA-mediated innate immune evasion strategy employed by ALV-J, enhancing our understanding of retroviral pathogenesis.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013552","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:38:49Z","timestamp":1760031529000},"page":"e1013552","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Avian leukosis virus subgroup J evades innate immunity by activating miR-155 to dually target TRAF3 and STAT1"],"prefix":"10.1371","volume":"21","author":[{"given":"Xinyue","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Defang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longying","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxing","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhai","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4323-2541","authenticated-orcid":true,"given":"Ziqiang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"issue":"1","key":"ppat.1013552.ref001","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0749-0720(15)30365-0","article-title":"Avian 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