eprintid: 38785
rev_number: 12
userid: 7543
dir: disk0/00/03/87/85
datestamp: 2020-07-30 18:35:21
lastmod: 2020-07-30 18:35:21
status_changed: 2020-07-30 18:35:21
type: thesis_degree
metadata_visibility: show
contact_email: ztk5@pitt.edu
item_issues_id: duplicate_title_38454
item_issues_type: duplicate_title
item_issues_description: Duplicate title to
Koenig, Zachary
Type III Interferon Control of Rift Valley Fever Virus at Epithelial Cell Barriers.
Master's Thesis, University of Pittsburgh.
(Unpublished)
item_issues_timestamp: 2020-04-25 06:02:30
item_issues_status: autoresolved
item_issues_count: 0
eprint_status: archive
creators_name: Koenig, Zachary
creators_email: ztk5@pitt.edu
creators_id: ztk5
title: Type III Interferon Control of Rift Valley Fever Virus at Epithelial Cell Barriers
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
keywords: RVFV, Rift Valley Fever Virus, Type III Interferon, Lambda
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.
date: 2020-07-30
date_type: published
pages: 63
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_chair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Hartman, Amy
etdcommittee_name: McElroy, Anita
etdcommittee_name: Mattila, Joshua
etdcommittee_email: hartman2@pitt.edu
etdcommittee_email: mcelroya@pitt.edu
etdcommittee_email: jmattila@pitt.edu
etd_defense_date: 2020-04-13
etd_approval_date: 2020-07-30
etd_submission_date: 2020-04-24
etd_release_date: 2020-07-30
etd_access_restriction: immediate
etd_patent_pending: FALSE
thesis_type: thesis
degree: MS
citation: Koenig, Zachary (2020) Type III Interferon Control of Rift Valley Fever Virus at Epithelial Cell Barriers. Master's Thesis, University of Pittsburgh. (Unpublished)
document_url: http://d-scholarship-dev.library.pitt.edu/38785/1/KoenigZ_MSthesis_April2020.pdf