Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.514097
Title: The role of scavenger receptor B-I in hepatitis C virus attachment and entry
Author: Grove, Joseph
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2009
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.514097  DOI: Not available
Keywords: RA Public aspects of medicine
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