Functional characterization of virus-kinase interactions during cellular entry of hepatitis C virus
type: Dataset
description: Hepatitis C virus (HCV) is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. Therapeutic options to treat chronic viral hepatitis are limited by high costs, side effects and viral resistance in most patients. HCV entry is the first step of interaction between the virus and the host cell. It is required for the initiation, propagation and maintenance of infection, making it a promising target for antiviral therapy. HCV entry requires the cooperative interaction of several cellular factors, including CD81 and claudin-1 (CLDN1). We have recently identified a role for EGF receptor (EGFR) and ephrin receptor A2 (EphA2) in HCV entry by regulating the formation of the co-receptor complex CD81-CLDN1, suggesting that the signaling of these receptors might play a role in viral entry. However, the precise mechanisms of regulation are unknown. We wanted to identify the molecular mechanisms of EGFR signaling required for the HCV entry process. We identify HRas as key host signaling transducer for HCV entry. Advanced imaging studies have revealed that HRas signaling can modulate the lateral diffusion and membrane trafficking of CD81. A modified diffusion of CD81 allows the assembly of the receptors complex. In addition, HRas associates with tetraspanin microdomains containing the host receptors CD81 and CLDN1 and HCV entry factors previously unknown: the integrin beta1 and Rap2B. HCV therefore exploits HRas signaling for cellular entry. These data improve our understanding of the molecular mechanisms of HCV entry induced by EGFR and open new perspectives for the development of antivirals targeting signaling pathways.
identifier: NNT: 2013STRAJ007
issued: 2026-05-09T11:12:51.095223
language: fr
modified: 2026-05-09T11:12:51.095228
contact point: Organization
  fn: CCSD
keyword: antiviral
keyword: cell-signaling
keyword: egf-receptor-egfr
keyword: entree-virale
keyword: foie
keyword: gtpase-hras
keyword: hepatitis-c-virus-hcv
keyword: hras-gtpase
keyword: infection
keyword: infoeu-reposemanticsdoctoralthesis
keyword: liver
keyword: recepteur-a-legf-egfr
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: signalisation-cellulaire
keyword: theses
keyword: viral-entry
keyword: virus-de-lhepatite-c-hcv
landing page: https://theses.hal.science/tel-00870549

Functional characterization of virus-kinase interactions during cellular entry of hepatitis C virus
type: Distribution
format: HTML
issued: 2026-05-09T11:12:51.122750
modified: 2026-05-09T11:12:51.066819
access URL: https://theses.hal.science/tel-00870549

test_moissonnage_selune
type: Agent