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Polyomavirus T antigens activate an antiviral state

Giacobbi, Nicholas (2014) Polyomavirus T antigens activate an antiviral state. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

The large T antigen (TAg) of the polyomavirus Simian virus 40 (SV40) is known to play an important role in several events during the viral life cycle, including DNA replication, transcription, and virion assembly. Recent analysis revealed that primary mouse embryonic fibroblasts (MEFs) expressing exogenous TAg showed increased transcription of interferon stimulated genes (ISGs). Interestingly, this activation was shown to be stimulated in the absence of interferon production. The mechanisms by which TAg upregulates the pathway(s) and the consequences of that upregulation remain unknown. Thus, investigation into this mechanism may allow the elucidation of novel host factors moderating the interferon response. I tested several mutants of TAg to understand what functions are necessary to induce the interferon response. My investigation has revealed that the early region of SV40 can activate an antiviral phenotype in MEFs, as seen by the attenuation of viral growth during productive infection. Furthermore, the amino terminus of TAg is sufficient to stimulate this response, and alternative splice forms from the early region (e.g. small T Antigen) do not seem to be critical to the upregulation of ISGs. Other experiments indicate that the STAT1 transcription factor is necessary for establishment of the antiviral state. I have also shown that two human polyomaviruses, Human Polyomavirus BK (BKV) and human Polyomavirus JC (JCV), follow suit with our observations of SV40 TAg. I hypothesize that the TAg-mediated activation of ISGs contributes to an environment inhibitory for viral growth and that this phenomenon is extended to multiple polyomaviruses. This research offers new insight into the interactions of polyomaviruses with its host. This new knowledge could be used in combating human disease, and therefore serves as a valuable contribution to public health.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Giacobbi, Nicholas nsg12@pitt.eduNSG12
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairReinhart, Todd A.reinhar@pitt.eduREINHAR
Committee MemberAyyavoo, Velpandivelpandi@pitt.eduVELPANDI
Committee MemberPipas, James Mpipas@pitt.eduPIPAS
Date: 29 September 2014
Date Type: Publication
Defense Date: 31 July 2014
Approval Date: 29 September 2014
Submission Date: 22 July 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 70
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: polyomavirus, sv40, isg, ifn.
Date Deposited: 29 Sep 2014 20:41
Last Modified: 15 Nov 2016 14:22
URI: http://d-scholarship.pitt.edu/id/eprint/22465

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