?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F38785%2F&rft.title=Type+III+Interferon+Control+of+Rift+Valley+Fever+Virus+at+Epithelial+Cell+Barriers&rft.creator=Koenig%2C+Zachary&rft.description=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%2C+resulting+in+hepatic+disease+and+hemorrhagic+fever.+One+of+the+most+devastating+characteristics+seen+in+previous+outbreaks+are+among+pregnant+livestock+which+experience+%E2%80%9Cabortion+storms%E2%80%9D+wherein+the+virus+induces+abortogenic+rates+of+90-100%25.+While+human+RVF+carries+a+small+risk+of+mortality%2C+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%2C+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%2C+mimicking+the+mosquito+bite+transmission+seen+in+natural+infections.+Type+III+interferons%2C+the+IFN-%CE%BB+family+of+proteins%2C+are+a+group+of+innate%2C+antiviral+molecules+that+function+in+modulating+host+immune+responses+to+viral+infection+at+epithelial+barriers%2C+including+the+placenta.+Unlike+type+I+interferons+which+elicit+antiviral+responses+in+all+nucleated+cells%2C+which+express+the+IFNAR1+receptor%2C+type+III+interferons+elicit+a+more+localized+innate+antiviral+response%2C+with+receptors+for+IFN-%CE%BB+proteins+only+found+on+barrier+epithelial+cells.+Previous+work+has+examined+a+type+III+interferon%2C+IFN-%CE%BB1%2C+and+its+ability+to+confer+protection+at+the+placental+barrier+during+Zika+virus+infection.+Primary+human+trophoblasts%2C+the+barrier+cells+of+the+placenta%2C+constitutively+release+IFN-%CE%BB1+which+protects+trophoblast+and+non-trophoblast+cells+from+Zika+virus+infection%2C+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.+%0D%0AWe+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%2C+cells+infected+with+wildtype+RVFV+or+RVFV-%CE%94NSs%2FGFP+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.&rft.date=2020-07-30&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F38785%2F1%2FKoenigZ_MSthesis_April2020.pdf&rft.identifier=++Koenig%2C+Zachary++(2020)+Type+III+Interferon+Control+of+Rift+Valley+Fever+Virus+at+Epithelial+Cell+Barriers.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++