Expression of intrahepatic interferon stimulated genes during chronic hepatitis C virus infection

    Research output: ThesisDoctoral Thesis

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    Abstract

    [Truncated] Hepatitis C virus (HCV) is estimated to chronically infect more than 170 million people worldwide. This important human infection causes chronic hepatitis in the majority of infected individuals and can be cured in 40-60% of patients by treatment with interferon-alpha (IFN-?) based therapies. Because of the apparent importance of IFN in eradicating HCV and the lack of knowledge concerning the intrahepatic interferon response to HCV, these studies have focused on host mRNA and protein expression for IFN effector pathways in liver tissue, the major site of viral replication. This study has analysed intrahepatic type 1 IFN response pathways during chronic HCV disease (chapter 3 and 4), during de nova HCV infection (chapter 5) and following treatment with IFN-? monotherapy (chapter 5). Viral factors that may interfere in the action of IFN are also considered (chapter 4 and 6). The studies evaluate the proposal that the IFN induced response of a person during chronic infection is indicative of the outcome that will occur on use of IFN-? based therapies. The endogenous interferon stimulated gene (ISG) response to chronic HCV infection was investigated through quantitation of intrahepatic mRNA levels of several ISG with known antiviral or immune regulatory activities including: MxA, PKR, 2,5 OAS, ISG15 and the chemokine, interleukin 8 (IL-8), using real-time RT-PCR (chapter 3). It was found that the level of intrahepatic ISG expression, but not IL-8, was significantly upregulated (p < 0.001) in chronic HCV disease (n = 44), compared to controls (n = 12), irrespective of the infecting HCV genotype. The levels of ISG mRNA did not predict the subsequent response of an individual to therapy with IFN-? and ribavirin.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • The University of Western Australia
    DOIs
    Publication statusUnpublished - 2002

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