Cartwright, Haley Nicole
(2022)
Pathogenesis and treatment of Rift Valley fever virus.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus causing periodic outbreaks of severe disease in humans and livestock. Currently endemic to most of Africa and the Arabian Peninsula, RVFV threatens to spread into new regions of the world due to its many competent mosquito vectors and the effects of climate change. Rift Valley fever (RVF) in humans generally causes a self-limiting febrile illness; however, it can progress to severe forms of disease including hepatitis, hemorrhagic fever, or encephalitis. Unhindered spread of RVFV would cause major human health and agricultural economic consequences. Therefore, RVFV is classified as a NIAID category A priority pathogen and a WHO priority disease for research and development. Despite this, the field lacks tractable high-throughput animal models of the various forms of RVFV disease and there are no licensed human therapeutics. Here I address these gaps in the RVFV field by developing and characterizing both novel mouse models and therapeutically relevant antibodies. First, I evaluate RVFV susceptibility and pathogenesis across five commonly used inbred laboratory mouse strains to determine phenotypic baselines, identify potential sex differences, and determine challenge dose. Second, I screen 20 recombinant inbred Collaborative Cross mouse strains to identify and characterize novel murine models of RVFV disease. Third, I develop RVFV monoclonal antibodies, establish therapeutic efficacy, and show that Fc-mediated functions are a critical component of humoral protection from RVFV. Together this work answers critical questions about RVFV pathogenesis and treatment. Importantly, this work yielded both a novel model of RVF encephalitis and multiple monoclonal antibody therapeutic candidates.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
1 June 2022 |
| Date Type: |
Publication |
| Defense Date: |
4 April 2022 |
| Approval Date: |
1 June 2022 |
| Submission Date: |
20 April 2022 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
159 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Microbiology and Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
mouse model, collaborative cross, encephalitis, monoclonal antibody, mAb |
| Date Deposited: |
01 Jun 2022 13:49 |
| Last Modified: |
19 May 2023 13:46 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42677 |
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