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dc.contributor.advisorAkkaraju, Giridhar
dc.contributor.authorHoge, Elli
dc.date2016-05-19
dc.date.accessioned2016-09-14T15:32:02Z
dc.date.available2016-09-14T15:32:02Z
dc.date.issued2016
dc.identifier.urihttps://repository.tcu.edu/handle/116099117/11330
dc.description.abstractHepatitis C Virus (HCV) infects liver cells in approximately 180 million people worldwide and will produce a chronic infection in roughly 85% of those affected. In order to develop more effective treatments for the disease, a more in-depth understanding of the mechanism the virus uses to block our immune response is needed. During a normal immune response, a signal transduction pathway turns on the Interferon-beta (IFN-beta) promoter, which makes proteins to elicit an inflammatory response to clear the body of the. HCV, which has an RNA-based genome that codes for both structural and non-structural proteins, blocks this pathway by an unknown mechanism. NS5A, one of the nonstructural proteins made by HCV, is known to block the IFN-beta promoter, but it is unclear which of the three transcription factors NS5A blocks-- ATF-2, IRF-3, and NF-kB-- or a combination of them. It is our hypothesis that HCV protein NS5A inhibits the activation of one or more of these transcription factors, allowing the virus to evade the immune system and establish a chronic infection. To test this hypothesis, 293HEK cells were transfected with the promoters of interest-- IFN-beta and NF-kB-- attached to a Luciferase reporter gene, which upon expression gives off light that can be measured using a luminometer. Next, the cells were co-transfected with NS5A and infected with Sendai virus (SV). Cells were harvested and the activity of the promoter was measured to determine if NS5A inhibits the activation of NF-kB. Our results suggest that NS5A inhibits the SV-induced activation of NF-kB but not the TNF-induced activation of NF-kB, possibly indicating that the step being inhibited by NS5A is unique to the virus-induced RIG-I signaling pathway. Identifying the exact step that NS5A inhibits could lead to the development of more effective antiviral drugs.
dc.subjectHepatitis C Virus
dc.subjectHCV
dc.subjectInterferon-Beta
dc.subjectIFN-B
dc.subjectNS5A
dc.subjectInnate Immunity
dc.subjectAntiviral pathway
dc.subjectNF-kB
dc.subjectTNF-a
dc.titleThe Effects of Hepatitis C Virus Protein, NS5A, on Transcription Factor, NF-kB
etd.degree.departmentBiology
local.collegeCollege of Science and Engineering
local.collegeJohn V. Roach Honors College
local.departmentBiology


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