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Current animal models, particularly AG129 mice, inadequately recapitulate human vascular pathology due to neurotropic confounding and reliance on mouse\u2010adapted strains. To address this translational gap, we generated interferon alpha\/beta receptor subunit 2 (\n                    <jats:italic>IFNAR2<\/jats:italic>\n                    ) knockout (KO) pigs via CRISPR\/Cas9 gene editing and somatic cell nuclear transfer. Four KO piglets were challenged intradermally with a DENV serotype 4 clinical isolate non\u2010pathogenic in AG129 mice. One animal died at 7 days post\u2010infection, exhibiting pleural effusion, ascites, and severe hemorrhagic lesions across multiple organs. Sustained viremia (10\u2075\u00b7\u00b9 copies\/mL) was accompanied by marked cytokine elevation (TNF\u2010\u03b1 255.1\u2009pg\/mL; IL\u201012p40 288.1\u2009pg\/mL), biochemical evidence of hepatocellular injury (AST 827.9\u2009U\/L) and renal dysfunction. Histopathology revealed widespread vascular endothelial necrosis without CNS involvement, closely resembling human severe dengue vasculopathy. The three remaining KO pigs showed only transient low\u2010level viremia without severe disease. Although limited to a single severe case, these findings provide proof\u2010of\u2010concept that\n                    <jats:italic>IFNAR2<\/jats:italic>\n                    KO pigs can recapitulate hallmark features of human severe dengue, offering a physiologically relevant large animal platform for pathogenesis research and therapeutic evaluation.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70980","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:34:39Z","timestamp":1779456879000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment of an\n                    <i>IFNAR2<\/i>\n                    Knockout Pig Model for Severe Dengue\u2010Like Pathology"],"prefix":"10.1002","volume":"98","author":[{"given":"Geon A.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Laboratory Science, School of Healthcare Science Eulji University Uijeongbu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Hee","family":"Yeon","sequence":"additional","affiliation":[{"name":"Department of Microbiology Ajou University School of Medicine Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology Ajou University School of Medicine Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Eulji University School of Medicine Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongjin","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Eulji University School of Medicine Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Min","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Eulji University School of Medicine Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-3693","authenticated-orcid":false,"given":"Su\u2010Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, College of Veterinary Medicine Konkuk University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Animal Care Yonam College Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"ABSolution Hwaseong Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-2248","authenticated-orcid":false,"given":"Seung\u2010Chai","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Jeonbuk National University Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwan\u2010Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Jeonbuk National University Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0465-0794","authenticated-orcid":false,"given":"Won\u2010Il","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Jeonbuk National University Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhoon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Eulji University School of Medicine Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung\u2010Shin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology Ajou University School of Medicine Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"W. 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