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HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex

Zona, L. and Lupberger, J. and Sidahmed-Adrar, N. and Thumann, C. and Harris, H. J. and Barnes, A. and Florentin, J. and Tawar, R. G. and Xiao, F. and Turek, M. and Durand, S. C. and Duong, F. H. and Heim, M. H. and Cosset, F. L. and Hirsch, I. and Samuel, D. and Brino, L. and Zeisel, M. B. and Le Naour, F. and McKeating, J. A. and Baumert, T. F.. (2013) HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex. Cell host & microbe, Vol. 13, H. 3. pp. 302-313.

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Official URL: http://edoc.unibas.ch/dok/A6338559

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:1931-3128
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:14
Deposited On:10 Apr 2015 09:14

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