|Title:||Host gene expression and its regulation by microRNA in HCV and HIV/HCV co-infection|
|Publisher:||University of Sydney.|
Infectious Diseases and Immunology.
Central Clinical School - RPAH.
|Abstract:||HCV infection is prevalent and long-term infection may lead to liver cirrhosis and hepatocellular carcinoma (HCC). HIV/HCV co-infection has been shown to accelerate progression of HCV associated liver disease, and HCV in exacerbating hepatotoxicity of antiretroviral therapy. Both viruses are able to manipulate the host gene expression (mRNA) and regulatory (miRNA) machinery. It remains unclear how the regulation of mRNA expression is governed in HCV-infected Peripheral Blood Mononuclear Cells (PBMC) and liver tissue (tumor and non-tumor). This may help explain the cross-talk between PBMC and liver for predicting early events guiding the development of cirrhosis and HCC. Differentially expressed (DE) genes and miRNAs in each group comparison were also validated by Polymerase Chain reaction (PCR). We identified significant interactions between the DE miRNAs and genes with Bayesian network analysis. Selected miRNA: mRNA interactions were validated with the dual luciferase reporter assay that showed negative regulatory effect on the gene targets. Overall, this study has helped to not only define the utility of PBMCs in predicting early genomic events guiding cirrhosis and HCC in liver tissue in HCV-infected patients, but also showed evidence for mono and co-infection specific genes and miRNAs, which may help develop new generation of biomarkers for prognosis.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|GUPTA Priyanka - Final thesis.pdf||12.78 MB||Adobe PDF|
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