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Impact of SR-BI and CD81 on Hepatitis C virus entry and evasion

Abstract : Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. In the first part of my PhD, we aimed to further characterize the role of scavenger receptor class B type I (SR-BI) in HCV infection. While the SR-BI determinants involved in HCV binding have been partially characterized, the post-binding function of SR-BI remains remained largely unknown. To further explore the role of HCV-SR-BI interaction during HCV infection, we generated a novel class of anti-SR-BI monoclonal antibodies inhibiting HCV infection. We demonstrated that human SR-BI plays a dual role in the HCV entry process during both binding and post-binding steps. Targeting the post-binding function of SR-BI thus represents an interesting antiviral strategy against HCV infection. In the second part of my PhD, we aimed to characterize the molecular mechanisms underlying HCV re-infection of the graft after liver transplantation (LT). We identified threeadaptive mutations in envelope glycoprotein E2 mediating enhanced entry and evasion of a highly infectious escape variant. These mutations markedly modulated CD81 receptor dependency resulting in enhanced viral entry. The identification of these mechanisms advances our understanding of the pathogenesis of HCV infection and paves the way for the development of novel antiviral strategies and vaccines.
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Submitted on : Sunday, April 28, 2013 - 1:00:43 AM
Last modification on : Friday, February 22, 2019 - 1:24:37 AM
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  • HAL Id : tel-00818590, version 1

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Muhammad Nauman Zahid. Impact of SR-BI and CD81 on Hepatitis C virus entry and evasion. Biochemistry, Molecular Biology. Université de Strasbourg, 2012. English. ⟨NNT : 2012STRAJ014⟩. ⟨tel-00818590⟩

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