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In vitro analyses of Merkel cell polyomavirus cell biology

Guastafierro, Anna (2013) In vitro analyses of Merkel cell polyomavirus cell biology. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The work described in this dissertation was initiated in 2008, shortly after the discovery of Merkel cell polyomavirus (MCV). MCV was discovered as clonally integrated in 80% of Merkel cell carcinoma (MCC) and tumor-derived viral genomes were found to harbor individual large T antigen (LT) truncating deletions. The work presented in this thesis focuses on two main features associated with MCV cell biology: (1) Viral replication requirements that promote viral origin replication in the context of full length MCV LT (chapter 3) and (2) cellular targets that enhance human fibroblast proliferation in the presence of tumor-derived full length LT (chapter 4). As part of these studies, the novel MCV-positive MCC cell line MS-1 was generated, and its cellular and viral features are presented here (chapter 2). MCC cell lines are useful tools that can be used to study MCV biology, and test therapeutic compounds in vitro, as well as in a xenograft setting in vivo as described in the appendix of this thesis. Within the past 6 years, 8 new human polyomaviruses have been identified through basic biological approaches, highlighting the possibility that other human malignancies may be associated with polyomaviral infections. The identification of MCV in association with an aggressive human cancer also underscores the relevance of basic research in understanding human disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Guastafierro, Annaang67@pitt.eduANG67
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMoore, Patrick Spsm9@pitt.eduPSM9
Committee MemberPipas, James Mpipas@pitt.eduPIPAS
Committee MemberBrodsky, Jeffrey Ljbrodsky@pitt.eduJBRODSKY
Committee MemberJenkins, Frank Jfjenkins@pitt.eduFJENKINS
Committee MemberSchwacha, Anthonyschwacha@pitt.eduSCHWACHA
Date: 26 August 2013
Date Type: Publication
Defense Date: 13 August 2013
Approval Date: 26 August 2013
Submission Date: 21 August 2013
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 229
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Merkel cell polyomavirus, Merkel cell carcinoma
Date Deposited: 26 Aug 2013 17:45
Last Modified: 15 Nov 2016 14:15
URI: http://d-scholarship.pitt.edu/id/eprint/19712

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