Investigating mechanisms of Hepatitis C virus endocytosis

Thorley, Jennifer (2014). Investigating mechanisms of Hepatitis C virus endocytosis. University of Birmingham. Ph.D.

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Abstract

Many viruses exploit and, in some cases, promote host cell endocytic pathways for infection. These pathways include caveolar and clathrin-mediated endocytosis, as well as macropinocytosis. The entry mechanisms of many viruses are not clear cut, with more than one pathway implicated in some cases. Hepatitis C virus (HCV) is a hepatotropic virus associated with liver disease, fibrosis, cirrhosis and hepatocellular carcinoma. There are four co-receptors or “entry factors” for HCV: the tetraspanin CD81, scavenger receptor BI (SR-BI and the tight junction proteins Claudin 1 (CLDN1) and Occludin (OCLN). Clathrin-dependent endocytosis of HCV has been demonstrated in hepatoma cell lines and has also been shown to be the route of entry for co-receptor CD81; however, other endocytic pathways have not been considered. This thesis investigates a role for caveolae in HCV entry. In addition, it has recently become apparent that the epidermal growth factor receptor (EGFR) is required for viral entry into hepatoma cells and that stimulation with EGF results in increased entry and infection. This thesis investigates the role of EGFR in the endocytosis and trafficking of HCV receptors/entry factors, with a particular focus on CD81, using live-cell and super-resolution imaging techniques.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):