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Article Dans Une Revue Cell Host and Microbe Année : 2013

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

Laetitia Zona
  • Fonction : Auteur
N Sidahmed-Adrar
  • Fonction : Auteur
Christine Thumann
  • Fonction : Auteur
H Harris
  • Fonction : Auteur
A Barnes
J Florentin
  • Fonction : Auteur
Rajiv G Tawar
  • Fonction : Auteur
Marine Turek
  • Fonction : Auteur
Sarah C Durand
  • Fonction : Auteur
M Heim
  • Fonction : Auteur
Cosset François-Loïc
I Hirsch
  • Fonction : Auteur
D Samuel
  • Fonction : Auteur
Laurent Brino
  • Fonction : Auteur
F Le Naour
  • Fonction : Auteur
J Mckeating
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-02494664 , version 1 (28-02-2020)

Identifiants

Citer

Laetitia Zona, Joachim Lupberger, N Sidahmed-Adrar, Christine Thumann, H Harris, et al.. HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex. Cell Host and Microbe, 2013, 13 (3), pp.302-313. ⟨10.1016/j.chom.2013.02.006⟩. ⟨hal-02494664⟩
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