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In this study we performed high-throughput sequencing on RNA extracted from macrophages that were exposed to RABV for 48 hours, and compared their transcriptional profiles to that of non-polarized macrophages (M0), and macrophages polarized towards the canonical M1, M2a and M2c phenotypes. Our analysis revealed that RABV-stimulated macrophages show high expression of several M1, M2a and M2c signature genes. Apart from their partial resemblance to these phenotypes, unbiased clustering analysis revealed that RABV induces a unique and distinct polarization program. Closer examination revealed that RABV induced multiple pathways related to the interferon- and antiviral response, which were not induced under other classical polarization strategies. Surprisingly, our data show that RABV induces an activated rather than a fully suppressed macrophage phenotype, triggering virus-induced activation and polarization. This includes multiple genes with known antiviral (e.g. APOBEC3A, IFIT\/OAS\/TRIM genes), which may play a role in anti-RABV immunity.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1013842","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T05:33:53Z","timestamp":1675143233000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Rabies virus uniquely reprograms the transcriptome of human monocyte-derived macrophages"],"prefix":"10.3389","volume":"13","author":[{"given":"Carmen W.E.","family":"Embregts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelieke S.","family":"Wentzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T. den","family":"Dekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred F.J.","family":"van IJcken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Stadhouders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine H.","family":"GeurtsvanKessel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq-a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"B2","volume-title":"matrixStats: Functions that apply to rows and columns of matrices (and to vectors)","author":"Bengtsson","year":"2021"},{"key":"B3","unstructured":"BligheK.\n            LunA.\n          PCAtools: Everything principal compenents analysis2021"},{"key":"B4","doi-asserted-by":"publisher","first-page":"001619","DOI":"10.1099\/jgv.0.001619","article-title":"Murine Ifit3 restricts the replication of rabies virus both in vitro and in vivo","volume":"102","author":"Chai","year":"2021","journal-title":"Journal of General Virology"},{"key":"B5","first-page":"357","article-title":"Experimental rabies in skunks: persistence of virus in denervated muscle at the inoculation site","volume":"45","author":"Charlton","year":"1981","journal-title":"Can. 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