HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex
| Autor: | Jonathan Florentin, François Le Naour, Francois H.T. Duong, Markus H. Heim, Fei Xiao, Jane A. McKeating, Amy Barnes, Christine Thumann, Helen J. Harris, Didier Samuel, Nazha Sidahmed-Adrar, Joachim Lupberger, François-Loïc Cosset, Thomas F. Baumert, Rajiv G. Tawar, Laetitia Zona, Sarah C. Durand, Marine Turek, Mirjam B. Zeisel, Laurent Brino, Ivan Hirsch |
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| Přispěvatelé: | Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Receptor complex
Cancer Research Tetraspanins viruses Plasma protein binding Hepacivirus Sciences du Vivant [q-bio]/Médecine humaine et pathologie Microbiology Receptor tyrosine kinase Tetraspanin 28 Proto-Oncogene Proteins p21(ras) 03 medical and health sciences 0302 clinical medicine Tetraspanin Virology Immunology and Microbiology(all) Claudin-1 Humans HRAS Molecular Biology 030304 developmental biology Host cell membrane 0303 health sciences biology Virus Internalization Hepatitis C 3. Good health Cell biology ErbB Receptors 030220 oncology & carcinogenesis biology.protein Cancer research Parasitology Signal transduction Protein Multimerization [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology CD81 Protein Binding Signal Transduction |
| Zdroj: | Cell Host and Microbe Cell Host and Microbe, Elsevier, 2013, 13 (3), pp.302-313. ⟨10.1016/j.chom.2013.02.006⟩ Cell host & microbe |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2013.02.006⟩ |
| Popis: | International audience; Hepatitis C virus (HCV) entry is dependent on coreceptor complex formation between the tetraspanin superfamily member CD81 and the tight junction protein claudin-1 (CLDN1) on the host cell membrane. The receptor tyrosine kinase EGFR acts as a cofactor for HCV entry by promoting CD81-CLDN1 complex formation via unknown mechanisms. We identify the GTPase HRas, activated downstream of EGFR signaling, as a key host signal transducer for EGFR-mediated HCV entry. Proteomic analysis revealed that HRas associates with tetraspanin CD81, CLDN1, and the previously unrecognized HCV entry cofactors integrin beta1 and Ras-related protein Rap2B in hepatocyte membranes. HRas signaling is required for lateral membrane diffusion of CD81, which enables tetraspanin receptor complex assembly. HRas was also found to be relevant for entry of other viruses, including influenza. Our data demonstrate that viruses exploit HRas signaling for cellular entry by compartmentalization of entry factors and receptor trafficking. |
| Databáze: | OpenAIRE |
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