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The roles of the neonatal Fc receptor and interferons in echovirus pathogenesis

Wells, Alexandra Isabella (2022) The roles of the neonatal Fc receptor and interferons in echovirus pathogenesis. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Enterovirus infections are major sources of disease in humans. Echoviruses are a major subtype of enteroviruses and are especially devastating to neonates and young children. Despite the number of infections and potential adverse outcomes, the basic determinants of pathogenesis for echoviruses is poorly understood. This dissertation describes the identification of the neonatal Fc receptor (FcRn) as the entry receptor for echoviruses and the subsequent development of new in vivo models that fully recapitulate echovirus disease as well as establish the role of interferons during echovirus infections. Collectively, these studies show (1) that human FcRn is the entry receptor for echoviruses, (2) that human FcRn and type I interferons mediate infection in the liver, (3) that type I and III interferons play differential roles in infection of the gastrointestinal tract and dissemination to other tissues, (4) the meninges of the brain are the main target of echovirus infection and (5) that the host interferon stimulated genes that target enteroviruses function in pan-enterovirus- and enterovirus-species specific manners.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wells, Alexandra IsabellaALW214@pitt.eduALW2140000-0001-8178-0376
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorCoyne, Carolyncarolyn.coyne@duke.edu
Committee ChairHand, Timothyhandt@pitt.edu
Committee MemberBakkenist, Christophercjb38@pitt.edu
Committee MemberDermody, Terenceterence.dermody@chp.edu
Committee MemberWilliam, Johnjvw@chp.edu
Date: 12 May 2022
Date Type: Publication
Defense Date: 28 February 2022
Approval Date: 12 May 2022
Submission Date: 25 March 2022
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 247
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: Echovirus, interferon
Date Deposited: 13 May 2022 02:59
Last Modified: 13 May 2022 02:59
URI: http://d-scholarship.pitt.edu/id/eprint/42411

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