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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp01jm214s26c
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dc.contributor.advisorPloss, Alexander-
dc.contributor.authorMadan, Vrinda-
dc.date.accessioned2021-08-20T15:14:05Z-
dc.date.available2023-07-03T12:00:08Z-
dc.date.created2021-04-16-
dc.date.issued2021-08-20-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/dsp01jm214s26c-
dc.description.abstractDengue virus (DENV), a potentially life-threatening disease affecting millions each year, remains a major global health threat. The scarcity of animal models mimicking human symptoms of DENV infection has slowed our understanding of disease pathogenesis and development of anti-viral therapies. Here, we investigate the use of previously established humanized HIS-NFA2/hFLT3LG mice to model immune responses following DENV infection. We first generated a diverse library of 20 infectious clones based on patient-derived viral strains—serving as an important tool for both this study and subsequent characterizations. Using two of these low-passage DENV clinical isolates, we demonstrate that HIS-NFA2/hFLT3LG mice can support viral replication. Additionally, these humanized mice display key clinical symptoms of DENV, including viremia and thrombocytopenia. We further characterized DENV-infected HIS-NFA2/hFLT3LG mice on the basis of their cellular and humoral immunity, finding that DENV-specific responses were activated similar to those seen in patients. In summary, we demonstrate that HIS-NFA2/hFLT3LG mice are susceptible to infection with clinical DENV clinical isolates, mount virus-specific adaptive immune response, and mimic key disease manifestations. Although additional refinements to the model are required, we anticipate that our HIS-NFA2/hFLT3LG system will be widely useful to mechanistically study DENV pathogenesis and for assessing the efficacy of anti-DENV therapeutics.en_US
dc.format.mimetypeapplication/pdf
dc.language.isoenen_US
dc.titleCharacterization and Optimization of Primary Dengue Viral Infection in a Humanized Mouse Modelen_US
dc.typePrinceton University Senior Theses
pu.embargo.terms2023-07-01-
pu.date.classyear2021en_US
pu.departmentMolecular Biologyen_US
pu.pdf.coverpageSeniorThesisCoverPage
pu.contributor.authorid920191706
pu.certificateGlobal Health and Health Policy Programen_US
pu.mudd.walkinYesen_US
Appears in Collections:Molecular Biology, 1954-2023
Global Health and Health Policy Program, 2017-2023

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