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Virus Versus Body: The Effect of the Hepatitis C Virus NS5A Protein on the Antiviral Response and Cancer Development

The Hepatitis C Virus (HCV) non-structural 5A protein (NS5A) has been studied for its ability to increase viral replication rates by repressing the host cell antiviral response and deregulating the host cell-cycle. Recent research conducted with NS5A mutants derived from the HCV replicon system demonstrated NS5A's capacity to repress activation of the IFN-beta promoter. Using luciferase assays, I compared the suppression capabilities of the NS5A mutants 10A and H27 with WT NS5A, revealing that WT NS5A suppresses the IFN-beta promoter more similar to the NS5A 10A mutant than the H27 mutant. I then used cell death assays to demonstrate NS5A's ability to block etoposide-induced cell death. To identify the mechanism by which NS5A is blocking cell death, I used cell death assays comparing cells expressing NS5A with cells lacking expression of the tumor-suppressor protein PKR, revealing that NS5A is must block cell death through interactions with a protein(s) other than PKR.

Identiferoai:union.ndltd.org:TCU/oai:etd.tcu.edu:etd-03162010-111213
Date16 March 2010
CreatorsCrenshaw, Molli Jones
ContributorsGiridhar Akkaraju
PublisherTexas Christian University
Source SetsTexas Christian University
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf, application/msword
Sourcehttp://etd.tcu.edu/etdfiles/available/etd-03162010-111213/
Rightsunrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to TCU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.

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