Please use this identifier to cite or link to this item:
http://arks.princeton.edu/ark:/88435/dsp01jm214s26c
Title: | Characterization and Optimization of Primary Dengue Viral Infection in a Humanized Mouse Model |
Authors: | Madan, Vrinda |
Advisors: | Ploss, Alexander |
Department: | Molecular Biology |
Certificate Program: | Global Health and Health Policy Program |
Class Year: | 2021 |
Abstract: | Dengue 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. |
URI: | http://arks.princeton.edu/ark:/88435/dsp01jm214s26c |
Type of Material: | Princeton University Senior Theses |
Language: | en |
Appears in Collections: | Molecular Biology, 1954-2024 Global Health and Health Policy Program, 2017-2023 |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
MADAN-VRINDA-THESIS.pdf | 2.83 MB | Adobe PDF | Request a copy |
Items in Dataspace are protected by copyright, with all rights reserved, unless otherwise indicated.