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

By Claire L Brimacombe, Joe Grove, Luke W Meredith, Ke Hu, Andrew J Syder, Maria Victoria Flores, Jennifer M Timpe, Sophie E Krieger, Thomas Baumert, Timothy L Tellinghuisen, Flossie Wong-Staal, Peter Balfe and Jane A McKeating

Abstract

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

Topics: R Medicine (General), QR355 Virology, QR180 Immunology, QR Microbiology
Publisher: American Society for Microbiology
Year: 2011
OAI identifier: oai:eprints.bham.ac.uk:510

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