Koenig, Zachary
(2020)
Type III Interferon Control of Rift Valley Fever Virus at Epithelial Cell Barriers.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Rift Valley fever virus (RVFV) is an emerging infectious disease of domesticated livestock that is endemic to many regions of Africa and is spread by multiple mosquito species. RVFV epizootic outbreaks commonly affect sheep and cattle, resulting in hepatic disease and hemorrhagic fever. One of the most devastating characteristics seen in previous outbreaks are among pregnant livestock which experience “abortion storms” wherein the virus induces abortogenic rates of 90-100%. While human RVF carries a small risk of mortality, RVFV is of great public health significance to women during pregnancy. An association has been demonstrated between women who are infected with RVFV and increased likelihood of late term miscarriage. Thus, RVFV infection in pregnant women carries the potential for vertical transmission to the child. Vertical transmission cases have been documented in naturally occurring outbreaks. Our lab has also demonstrated vertical transmission in a pregnant rat model of RVFV congenital infection. Pregnant rats were inoculated with wildtype RVFV subcutaneously, mimicking the mosquito bite transmission seen in natural infections. Type III interferons, the IFN-λ family of proteins, are a group of innate, antiviral molecules that function in modulating host immune responses to viral infection at epithelial barriers, including the placenta. Unlike type I interferons which elicit antiviral responses in all nucleated cells, which express the IFNAR1 receptor, type III interferons elicit a more localized innate antiviral response, with receptors for IFN-λ proteins only found on barrier epithelial cells. Previous work has examined a type III interferon, IFN-λ1, and its ability to confer protection at the placental barrier during Zika virus infection. Primary human trophoblasts, the barrier cells of the placenta, constitutively release IFN-λ1 which protects trophoblast and non-trophoblast cells from Zika virus infection, suggesting the virus must use alternative pathways to cross the placental barrier. The research presented herein represents the first investigations performed to define the possible modulatory effects of type III IFNs on RVFV pathogenesis.
We performed experiments in vitro in cell lines mimicking the hepatic and placental tropism for RVFV infections. Exogenous treatment with interferon revealed that type III IFN can reduce viral titers in infected cells in a time- and cell-dependent manner. Further, cells infected with wildtype RVFV or RVFV-ΔNSs/GFP exhibited modulated IFN stimulated gene (ISG) expression. The research presented herein represents the first investigations performed to define the possible modulatory effects of type III IFNs on RVFV pathogenesis.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
30 July 2020 |
| Date Type: |
Publication |
| Defense Date: |
13 April 2020 |
| Approval Date: |
30 July 2020 |
| Submission Date: |
24 April 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
63 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
RVFV, Rift Valley Fever Virus, Type III Interferon, Lambda |
| Date Deposited: |
30 Jul 2020 18:35 |
| Last Modified: |
30 Jul 2020 18:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38785 |
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