The role of scavenger receptor B-I in hepatitis C virus attachment and entry.

Grove, Joseph (2009). The role of scavenger receptor B-I in hepatitis C virus attachment and entry. University of Birmingham. Ph.D.

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Abstract

Hepatitis C Virus (HCV) poses a global health problem, leading to progressive disease often culminating in conditions such as hepatocellular carcinoma. HCV has a propensity to persist, with 70-80% of infected individuals failing to clear the virus. Recent evidence suggests that HCV entry is dependent on at least three cellular entry factors: CD81, Scavenger Receptor B-I (SR-BI) and Claudin-1. SR-BI is a receptor for high density lipoprotein (HDL), it is predominantly expressed in the liver and steroidogenic tissue. HCV is believed to interact with SR-BI via the viral envelope protein E2, interestingly the SR-BI ligand HDL enhances HCV infection. In this study we have investigated the interaction of HCV soluble glycoprotein with cell expressed SR-BI. We have shown that over expression of SR-BI in human hepatoma cells enhances HCV infection, indicating that SR-BI surface expression levels limit infection. Furthermore, anti-SR-BI serum inhibits HCV. We demonstrate that a cell culture adapted HCV mutant has a reduced dependency on SR-BI. This altered receptor dependency is accompanied by an increased sensitivity to neutralisation by soluble CD81 and enhanced binding of E2 to cell surface expressed CD81. The adapted variant also exhibits an altered relationship with lipoproteins and a heightened sensitivity to neutralising antibodies.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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