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Pathways deployed by human placental trophoblasts to confer viral resistance

Bayer, Avraham (2016) Pathways deployed by human placental trophoblasts to confer viral resistance. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

During pregnancy, the placenta plays a vital role in protecting the developing fetus from microbial infections. The multinucleated and terminally differentiated syncytiotrophoblasts actively coordinate host defense through a multitude of mechanisms. In addition to forming a cellular barrier, the syncytiotrophoblasts release extracellular vesicles containing microRNAs from the chromosome 19 microRNA cluster (C19MC). These vesicle-packaged miRNAs, upon uptake by recipient cells, induce autophagy and limit viral infection, acting against a diverse panel of both DNA and RNA viruses. We have shown that medium conditioned by primary human trophoblast (PHT) cells, which contain these vesicles, confers resistance from pathogens associated with congenital infections to recipient non-placental cells. Furthermore, we have demonstrated that primary human trophoblasts constitutively produce interferon lambda 1 (IFNλ1), leading to a robust induction of interferon stimulated genes in an autocrine and paracrine manner. These parallel pathways, actively coordinated by PHT cells, contribute to the barrier function of the placenta, protecting the developing fetus from viral infections.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bayer, AvrahamBayerava@pitt.eduBAYERAVA
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberCoyne, CarolynCoynec2@pitt.edu
Committee MemberKhan, SaleemKhan@pitt.edu
Committee MemberKinchington, PaulKinch@pitt.edu
Committee MemberGaffen, SarahSarah.Gaffen@pitt.edu
Committee ChairSadovsky, Yoelysadovsky@mwri.magee.edu
Date: 6 December 2016
Date Type: Publication
Defense Date: 7 September 2016
Approval Date: 6 December 2016
Submission Date: 11 November 2016
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 146
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Virology and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Placenta, Trophoblast, C19MC, miRNAs, IFN lambda
Date Deposited: 06 Dec 2016 20:54
Last Modified: 07 Dec 2016 06:15
URI: http://d-scholarship.pitt.edu/id/eprint/30296

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