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Exploring these alternative host defenses is crucial for\n                        understanding the complete arsenal that mammalian hosts deploy to combat\n                        viral disease, as IFN responses undoubtedly work in concert with other\n                        antiviral defenses to achieve virus restriction. Here, we discuss selected\n                        examples of antiviral factors and pathways in mammals that are not\n                        classically associated with the IFN response. These defenses range from\n                        constitutively expressed host restriction factors that directly inhibit\n                        specific steps of the viral life cycle to signaling pathways that invoke\n                        IFN-independent antiviral gene expression programs to cell death mechanisms\n                        that sacrifice the infected cell to prevent viral spread. Ultimately, our\n                        goal is to highlight the diversity of IFN-independent antiviral defenses\n                        that mammalian hosts utilize to block viral infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01707-24","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:00:45Z","timestamp":1760965245000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Mammalian innate antiviral defenses: beyond                    interferon"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1057-3836","authenticated-orcid":false,"given":"Emily A.","family":"Rex","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy M.","family":"Shaffer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-4152","authenticated-orcid":true,"given":"Don B.","family":"Gammon","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-092818-015756"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02582-24"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.025"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1273604"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","unstructured":"McDougal MB De Maria AM Ohlson MB Kumar A Xing C Schoggins JW. 2023. 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