Hepatitis C virus modulation of lipid and autophagy pathways

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dc.contributor.advisor Fanning, Liam J. en
dc.contributor.advisor Crosbie, Orla en
dc.contributor.advisor Kenny-Walsh, Elizabeth en
dc.contributor.author Harty, Ciara
dc.date.accessioned 2016-09-16T11:38:30Z
dc.date.issued 2016
dc.date.submitted 2016
dc.identifier.citation Harty, C. 2016. Hepatitis C virus modulation of lipid and autophagy pathways. PhD Thesis, University College Cork. en
dc.identifier.uri http://hdl.handle.net/10468/3095
dc.description.abstract Hepatitis C virus [HCV] infects 170 million people worldwide. We investigated interactions between HCV proteins and cellular proteins involved in autophagy and lipid metabolism. We sought to develop an infection model using patient derived human serum containing HCV and human hepatocytes, Huh7 cells. Using the model, we have shown intracellular expression of incoming HCV RNA (5′ UTR region and region spanning the E1/E2 glycoproteins), expression of the HCV proteins, core and NS5B, and a cellular response to HCV infection. These data suggests this model can be used to analyse the early stage of HCV infection. HCV utilises the autophagy pathway to both establish infection and to complete its life cycle. We investigated HCV interaction with the early stage autophagy protein ATG5. We found that although ATG5 mRNA is unchanged in HCV infected cells, protein expression of ATG5 is significantly upregulated. These data indicated HCV controls the post-transcriptional regulation of ATG5. We used the upstream open reading frame (uORF) and the 5′ UTR region of ATG5 to examine the post-transcriptional regulation. Our data suggest HCV RNA replication either directly or indirectly causes post-transcriptional regulation of the early autophagy protein, ATG5 in a 5′ UTR and uORF independent manner. HCV infection leads to an increase in SREBP controlled genes e.g. HMG-CoA Reductase, cholesterol, LDL and fatty acid synthesis. We hypothesised that HCV infection causes the activation of SREBP pathway by interacting directly or indirectly with proteins involved in the initiation of the pathway. We sought to determine if HCV interacts with SCAP or INSIG. We confirmed a change in LD distribution and HMG-CoA reductase activity as a result of HCV RNA replication. Significantly, we show SCAP protein expression was also altered during HCV RNA replication and HCV core protein possibly interacts with SCAP. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2016, Ciara Harty. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Hepatitis C virus en
dc.subject Autophagy en
dc.subject Lipid metabolism en
dc.title Hepatitis C virus modulation of lipid and autophagy pathways en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral Degree (Structured) en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en
dc.check.info Indefinite en
dc.check.date 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Molecular Medicine Ireland en
dc.description.status Not peer reviewed en
dc.internal.school Medicine en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat E-thesis on CORA only en
dc.internal.conferring Autumn 2016 en

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© 2016, Ciara Harty. Except where otherwise noted, this item's license is described as © 2016, Ciara Harty.
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