| dc.description.abstract | Hepatitis C Virus infects hepatocytes in humans. Infection with the virus yields a range of symptoms from asymptomatic to liver disease or hepatocellular carcinoma. The virus is estimated to be infecting 3% of the world's population and transmits via contaminated blood. There are current treatments for the virus, but they are not ideal because of their extreme side effects. Achieving a greater understanding of the virus and viral proteins can generate new ways to inhibit viral replication and progression of disease. To improve its reproductive success, HCV inhibits the immune system of the host. Specifically, HCV inhibits the antiviral response by decreasing the expression of IFN-b, a cytokine that activates the host defense against a pathogen. Three transcription factors, ATF-2, NFkB and IRF-3, are activated by viral infection, which stimulates the transcription factors to translocate to the nucleus to bind to the IFN-b promoter and turn on expression of IFN-b gene. An HCV protein, NS5A, is known to inhibit the expression of IFN-b, possibly by inhibiting transcription factor translocation. The effect of NS5A on the localization of each transcription factor pre- and post-viral infection was examined. NS5A inhibits translocation of one of the transcription factors, NFkB, but does not inhibit translocation of the other two, ATF-2 nor IRF-3. This supports the hypothesis that NS5A decreases the expression of IFN-b by inhibiting transcription factor, NFkB, from entering the nucleus and binding to the IFN-b promoter. | |
