{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:11:55Z","timestamp":1792843915636,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Institute of Human Virology, University of Maryland School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, which exhibit poor hematopoiesis for some cell populations. This study compares three humanized (hu) NOD-derived mouse models for dengue virus-2 (DENV-2) infection in the context of human cytokine expression. Three mouse strains (hu-NSG, hu-EXL, and hu-SGM3) received xenotransplants of human CD34+ fetal cord blood cells from a single donor, and one mouse strain received human peripheral blood mononuclear cells (hu-SGM3-PBMCs). All models exhibited infectious viruses in blood confirmed by plaque assay, but mice expressing human cytokines showed higher viremia compared to conventional NSG mice. The hu-SGM3-PBMCs model developed lethal infections, showing a significant increase in viremia and clinical signs. A detectable human cytokine response was observed in all the DENV-2-infected humanized mouse models. In conclusion, humanized NOD-derived mouse models expressing human cytokines offer a relevant platform for the study of dengue pathogenesis and antiviral therapies.<\/jats:p>","DOI":"10.3390\/pathogens13080639","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T17:08:34Z","timestamp":1722359314000},"page":"639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2767-6134","authenticated-orcid":false,"given":"Hernando","family":"Gutierrez-Barbosa","sequence":"first","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Facultad de Biolog\u00eda, Universidad de Antioquia, Bogot\u00e1 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Medina-Moreno","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-8306","authenticated-orcid":false,"given":"Federico","family":"Perdomo-Celis","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Davis","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-4672","authenticated-orcid":false,"given":"Joel V.","family":"Chua","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1931-6147","authenticated-orcid":false,"given":"Juan C.","family":"Zapata","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0140-6736(23)02576-X","article-title":"Dengue","volume":"403","author":"Adams","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/s41564-019-0476-8","article-title":"The current and future global distribution and population at risk of dengue","volume":"4","author":"Messina","year":"2019","journal-title":"Nat. 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