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Hepatitis C: transcriptional response and interferon signalling in human liver

Boldanova, Tujana. Hepatitis C: transcriptional response and interferon signalling in human liver. 2016, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12167

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Abstract

Hepatitis C virus (HCV) is widely used to investigate host-virus interactions. Cellular responses to HCV infection have been extensively studied in vitro. However, in human liver, interferon (IFN) stimulated gene expression can mask direct transcriptional responses to infection. To better characterize the direct effects of HCV infection in vivo, we analyze the transcriptomes of HCV-infected patients lacking an activated endogenous IFN system. We show that expression changes observed in these patients predominantly reflect immune cell infiltrates rather than cell-intrinsic pathways. We also investigate the transcriptomes of patients with endogenous IFN activation, which paradoxically cannot eradicate viral infection. We find that most IFN-stimulated genes are induced by both recombinant IFN therapy and the endogenous IFN system, but with lower induction levels in the latter, indicating that the innate immune response in chronic hepatitis C is too weak to clear the virus. We show that coding and non-coding transcripts have different expression dynamics following IFN treatment. Several microRNA precursors, including miR-122, are significantly down-regulated in response to IFN treatment, suggesting a new mechanism for IFN-induced expression fine-tuning.
Advisors:Heim, Markus H. and Hall, Michael N.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hepatologie > Hepatologie (Heim)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hepatologie > Hepatologie (Heim)
UniBasel Contributors:Heim, Markus H. and Hall, Michael N.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12167
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (101 Seiten)
Language:English
Identification Number:
Last Modified:22 Jan 2018 15:52
Deposited On:18 Jul 2017 14:26

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