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Among them, IL\u201019 is upregulated in response to viral infections, yet its functional significance and mechanistic basis have been poorly defined. This study identifies an unforeseen antiviral activity of IL\u201019. Mechanistically, we demonstrate that IL\u201019 signals through the IL\u201020RB receptor to drive STAT3 phosphorylation, and this activated IL\u201020RB\/STAT3 pathway then induces TRIM22 expression, culminating in enhanced IFN\u2010\u03bb secretion and the direct suppression of viral replication. Importantly, despite significantly curtailing HSV\u20101 replication in murine brain and lung tissues, IL\u201019 administration failed to confer a survival benefit, an effect attributable to aggravated pulmonary inflammation. These findings clarify IL\u201019 as a dual\u2010function cytokine with both protective antiviral and detrimental proinflammatory properties, illustrating the intricate immunomodulatory functions of cytokines during viral infections.<\/jats:p>","DOI":"10.1002\/jmv.71066","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:18:28Z","timestamp":1784531908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL\u201019 Modulates Antiviral Immunity and Inflammation via IL\u201020RB\/STAT3\/TRIM22 Signaling Pathway"],"prefix":"10.1002","volume":"98","author":[{"given":"Xinyu","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Song","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjuan","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirong","family":"Han","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010Sen University Shenzhen China"},{"name":"Shenzhen Key Laboratory of Pathogen Microbes and Biosafety Shenzhen campus of Sun Yat\u2010Sen University Shenzhen China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat\u2010Sen University), Ministry of Education Guangzhou China"},{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development, School of Pharmaceutical Sciences Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Wang","sequence":"additional","affiliation":[{"name":"North China Pharmaceutical Group New Drug Research and Development Co. 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