Hepatitis C Virus Induces Epidermal Growth Factor Receptor Activation via CD81 Binding for Viral Internalization and Entry
Autor: | Lauri Diehl, Gabriele Schaefer, Sharookh B. Kapadia, Jingyu Diao, László G. Kömüves, Homer Pantua, Hai Ngu |
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Rok vydání: | 2012 |
Předmět: |
Hepatitis C virus
media_common.quotation_subject Immunology Hepacivirus Biology Endocytosis medicine.disease_cause Microbiology Tetraspanin 28 Cell Line Tumor Virology Claudin-1 medicine Humans ERBB3 Epidermal growth factor receptor RNA Small Interfering Internalization Protein Kinase Inhibitors media_common virus diseases Virus Internalization digestive system diseases Virus-Cell Interactions ErbB Receptors Cell culture Insect Science Cancer research biology.protein RNA Viral Cyclin-dependent kinase 8 RNA Interference CD81 |
Zdroj: | Journal of Virology. 86:10935-10949 |
ISSN: | 1098-5514 0022-538X |
Popis: | While epidermal growth factor receptor (EGFR) has been shown to be important in the entry process for multiple viruses, including hepatitis C virus (HCV), the molecular mechanisms by which EGFR facilitates HCV entry are not well understood. Using the infectious cell culture HCV model (HCVcc), we demonstrate that the binding of HCVcc particles to human hepatocyte cells induces EGFR activation that is dependent on interactions between HCV and CD81 but not claudin 1. EGFR activation can also be induced by antibody mediated cross-linking of CD81. In addition, EGFR ligands that enhance the kinetics of HCV entry induce EGFR internalization and colocalization with CD81. While EGFR kinase inhibitors inhibit HCV infection primarily by preventing EGFR endocytosis, antibodies that block EGFR ligand binding or inhibitors of EGFR downstream signaling have no effect on HCV entry. These data demonstrate that EGFR internalization is critical for HCV entry and identify a hitherto-unknown association between CD81 and EGFR. |
Databáze: | OpenAIRE |
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