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|Title:||Characterization of the Role of Type I and III Interferon Receptor Signaling in Controlling Flavivirus Infection and the Development of Tools for Tracking Virally Infected Cells In Vivo|
|Authors:||Soto Albrecht, Yentli Elis|
|Abstract:||Yellow fever virus (YFV) is an arbovirus that contributes significantly to human morbidity and mortality. The live-attenuated YFV vaccine strain, YFV-17D, is derived from the virulent YFV Asibi clinical isolate. One of the most efficient vaccines ever developed, YFV-17D represents a prototypical flavivirus convenient for the study of host control of infection. Although the role of type I and II IFNs in controlling YFV-17D infection has been previously described in vivo, the role of type III IFN is incompletely understood. We characterized the clinical phenotype of mice deficient for type I, type III, and type I and III IFN receptors upon challenge with YFV-17D. We observed that type III IFN contribution to the control of YFV-17D infection was additive to type I as only type I-III IFN knock-out (KO) mice exhibited a significant mortality (>50%). Although both type I and type I-III KO mice displayed high viral load in serum and evidence of adaptive immune response activation, type I-III KO mice showed significant viral neuroinvasion and partial evasion of the adaptive immune response. In this work, we propose a model where type III IFN signaling is critical in preventing blood brain barrier permeability during failure of the type I IFN-mediated innate immune response against YFV-17D. In tandem, we recognized the general dearth of molecular tools for the study of host immune control of YFV-17D infection, and made progress in developing two tools for this purpose. A YFV-17D recombinant reporter strain and a platform for the detection of intracellular YFV-17D RNA in single cells, while unique in their use and applicability to in vitro and in vivo experimentation, will nonetheless prove valuable tools for the investigation of host and flavivirus biology.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Molecular Biology, 1954-2017|
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