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Neutralizing Antibody-Resistant Hepatitis C Virus Cell-to-Cell Transmission

Brimacombe, Claire L and Grove, Joe and Meredith, Luke W and Hu, Ke and Syder, Andrew J and Flores, Maria Victoria and Timpe, Jennifer M and Krieger, Sophie E and Baumert, Thomas and Tellinghuisen, Timothy L and Wong-Staal, Flossie and Balfe, Peter and McKeating, Jane A (2011) Neutralizing Antibody-Resistant Hepatitis C Virus Cell-to-Cell Transmission. Journal of Virology, 85 (1). (In Press)

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URL of Published Version: http://jvi.asm.org/cgi/reprint/JVI.01592-10v1

Identification Number/DOI: 10.1128/JVI.01592-10

Hepatitis C virus (HCV) can initiate infection by cell-free particle and cell-cell contact-dependent transmission. In this study we use a novel infectious coculture system to examine these alternative modes of infection. Cell-to-cell transmission is relatively resistant to anti-HCV glycoprotein monoclonal anti- bodies and polyclonal immunoglobulin isolated from infected individuals, providing an effective strategy for escaping host humoral immune responses. Chimeric viruses expressing the structural proteins rep- resenting the seven major HCV genotypes demonstrate neutralizing antibody-resistant cell-to-cell trans- mission. HCV entry is a multistep process involving numerous receptors. In this study we demonstrate that, in contrast to earlier reports, CD81 and the tight-junction components claudin-1 and occludin are all essential for both cell-free and cell-to-cell viral transmission. However, scavenger receptor BI (SR-BI) has a more prominent role in cell-to-cell transmission of the virus, with SR-BI-specific antibodies and small-molecule inhibitors showing preferential inhibition of this infection route. These observations highlight the importance of targeting host cell receptors, in particular SR-BI, to control viral infection and spread in the liver.

Type of Work:Article
Date:January 2011 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:American Society for Microbiology
ID Code:510
Refereed:YES
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