{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:24:16Z","timestamp":1783110256129,"version":"3.54.6"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The dengue virus (DENV) is a public health threat to humans. Increased vascular permeability, coagulopathy, and hemorrhagic diathesis are the pathophysiological hallmarks of severe dengue. However, although the interferon (IFN)\u2010mediated innate immune response forms the backbone of cell\u2010autonomous defense against pathogens, the exact IFN\u2010stimulated genes (ISGs) involved in DENV infection remain to be determined. The present study collected transcriptomic data sets of peripheral blood mononuclear cells from DENV patients and healthy volunteers from public data repositories. Also, lentivirus and plasmid were used to overexpress and knockdown IFI27. Initially, differentially expressed genes were filtered, and gene set enrichment analysis (GSEA) was performed to assess related pathways. Subsequently, the least absolute shrinkage and selection operator regression and support vector machine\u2010recursive feature elimination algorithms were used to screen crucial genes. The receiver operating characteristic curve analysis was then employed to test diagnostic efficacy. Next, CIBERSORT was used to analyze immune infiltration in 22 immune cell subsets. Additionally, to dissect high\u2010resolution molecular phenotypes directly from individual cells and the cellular interactions between immune cell subpopulations, single\u2010cell RNA sequencing (scRNA\u2010seq) was performed. We found that the IFN\u2010stimulated gene IFN\u2010\u03b1\u2010inducible protein 27 (<jats:italic>IFI27<\/jats:italic>) was highly expressed in dengue patients by leveraging bioinformatics analysis and machine learning algorithms. This finding was further validated in two independent published databases. In addition, <jats:italic>IFI27<\/jats:italic> overexpression positively regulated DENV\u20102 infection, whereas <jats:italic>IFI27<\/jats:italic> knockdown has the opposite effect. Consistently, scRNA\u2010seq analysis supported this conclusion, along with further dissection of increased <jats:italic>IFI27<\/jats:italic> expression mainly concentrated in monocytes and plasmacytoid dendritic cells. We also demonstrated that <jats:italic>IFI27<\/jats:italic> inhibited dengue infection. Moreover, <jats:italic>IFI27<\/jats:italic> was positively correlated with monocytes, M1 macrophages, activated dendritic cells, plasma cells, and resting mast cells and negatively correlated with CD8 T cells, \u03b3\u03b4 T cells, and na\u00efve B cells. GSEA revealed that <jats:italic>IFI27<\/jats:italic> was primarily enriched in the innate immune response, regulation of the viral life cycle, and JAK\u2010STAT signaling pathway. Notably, the interactions between LGALS9 and its receptor CD47 were markedly increased in dengue patients compared to healthy controls, based on cell\u2010cell communication analysis. Our findings reveal, for the first time, that <jats:italic>IFI27<\/jats:italic> is a key ISG in DENV infection. Given that the innate immune system plays a significant role in antagonizing DENV invasion, while ISGs are the ultimate antiviral effectors, <jats:italic>IFI27<\/jats:italic> may serve as a potential diagnostic marker and therapeutic target in dengue, although further validation is warranted.<\/jats:p>","DOI":"10.1002\/jmv.28706","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T09:59:06Z","timestamp":1679911146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Integrative bulk and single\u2010cell transcriptome profiling analysis reveals <i>IFI27<\/i> as a novel interferon\u2010stimulated gene in dengue"],"prefix":"10.1002","volume":"95","author":[{"given":"Cheng","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Hubei Hospital of Traditional Chinese Medicine Hubei University of Chinese Medicine Wuhan Hubei P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Huanggang Hospital of Traditional Chinese Medicine Hubei University of Chinese Medicine Huanggang Hubei P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-9647","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hubei Hospital of Traditional Chinese Medicine Hubei University of Chinese Medicine Wuhan Hubei P. R. 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