EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy

Lupberger, J. et al. (2011) EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nature Medicine, 17(5), pp. 589-595. (doi:10.1038/nm.2341) (PMID:21516087) (PMCID:PMC3938446)

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Abstract

Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Patel, Professor Arvind
Authors: Lupberger, J., Zeisel, M.B., Xiao, F., Thumann, C., Fofana, I., Zona, L., Davis, C., Mee, C.J., Turek, M., Gorke, S., Royer, C., Fischer, B., Zahid, M.N., Lavillette, D., Fresquet, J., Cosset, F.-L., Rothenberg, S.M., Pietschmann, T., Patel, A.H., Pessaux, P., Doffoël, M., Raffelsberger, W., Poch, O., McKeating, J.A., Brino, L., and Baumert, T.F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Medicine
Publisher:Nature Publishing Group
ISSN:1078-8956
ISSN (Online):1546-170X
Published Online:24 April 2011

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