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The role of Claudin-CD81 Co-Receptor interaction(s) in Hepatitis C virus entry

Davis, Christopher A (2011)
Ph.D. thesis, University of Birmingham.

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Hepatitis C Virus (HCV) infection is a hepatotropic, enveloped virus with a positive sense RNA genome. The prevalence rate of the virus has been shown to be 2.9% of the world population, equating to around 170 million infected individuals. Due to the high level of chronic infection and progressive nature of the liver disease, HCV is a major health concern.

Four host proteins have so far been indicated as viral receptors; scavenger receptor BI, CD81, Claudin1 and Occludin. The interaction of CD81 and Claudin1 has been previously demonstrated which lead us to determine whether specific interactions are essential for HCV entry.
Using a combination of imaging and biochemical methods we were able to demonstrate that only receptor active Claudins specifically interacted with CD81. We also evaluated the ability of previously published Claudin1 mutants to interact with CD81 and demonstrated that receptor inactive mutants no longer form an association with CD81. A bioinformatic model predicted the association of the T149, E152 and T153 residues of CD81 EC2 with the 62-66 region of Claudin1. Mutation of these residues lead to an ablation of Claudin1 association and a reduction in on HCV entry, further indicating the requirement of the Claudin1-CD81 complex in the entry process.

Type of Work:Ph.D. thesis.
Supervisor(s):McKeating, Jane A. and Balfe, Peter
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:RA Public aspects of medicine
Institution:University of Birmingham
ID Code:2844
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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