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Title: The role of CD81 in hepatoma biology and hepatitis C virus infection
Author: Brimacombe, Claire
ISNI:       0000 0004 2712 0248
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2011
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Hepatitis C Virus (HCV) is a global health problem, with over 170 million infected individuals worldwide. 70-80% of infected individuals develop progressive disease, and approximately 2% of these acquire hepatocellular carcinoma (HCC). HCV entry is dependent on tetraspanin CD81, scavenger receptor BI, and tight junction proteins claudin-1 and occludin. Tetraspanins are involved in multiple biological functions including cell-ECM adhesion and motility. An actin polymerization-dependent cell spread was observed upon ligation of CD81 on hepatoma cells. Importantly, HCV infection perturbed CD81-dependent cell spread, suggesting HCV infection may modulate CD81 function in hepatoma cells. Functional assays demonstrated that CD81 expression and HCV infection promote hepatoma cell motility. These findings allude to a link between HCV infection and associated HCC development. Establishment of a chronic infection demonstrates that HCV can escape from the host adaptive immune responses. We developed an in vitro cell culture system to monitor viral transmission in the presence of neutralizing antibodies (nAb). Separation of producer and target cells ablated nAb resistant transmission, suggesting that cell-cell contact was essential. Furthermore nAb resistant transmission was dependent upon all four co-receptors. These observations confirm HCV immune evasion by cell-to-cell transfer and have major implications for anti-glycoprotein targeted therapies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QM Human anatomy ; QR Microbiology ; RA0421 Public health. Hygiene. Preventive Medicine ; RB Pathology ; RZ Other systems of medicine