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

By J. Lupberger, M. Zeisel, Fei Xiao, C. Thumann, Isabel Fofana, Laetitia Zona, Christopher Davis, C. Mee, Marine Turek, S. Gorke and 16 more. Nature Medicine, 2011

728 citations recorded by the source corpus.

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.

Subfields: Analytical Chemistry, Cellular and Molecular Neuroscience, Hepatology

View Paper: https://www.semanticscholar.org/paper/e6ad343730ca9b87959e516faba0b836c459636b

Citations in the corpus

• Endocytosis, Signaling, and Beyond (2014, neutral): “This stimulates the expression of lysosome biogenesis and function, thus facilitat- Starvation Lysosomal stress Autophagosome Autophagy Signali ng S ign alin g Tumor progression + + + ++ ++ + Exosome releaseD Caveolar endocytosis RCP TP53 Recycling Integrins EGFR Lysosome Lysosome biogeneis/ functio”