003) 3aQ100μM: 5054±3552(p<00006)] In these cells’the typical

003) 3aQ100μM: 505.4±355.2(p<0.0006)]. In these cells'the typical localization of the core protein around the LDs was almost fully inhibited by quercetin, Core protein rather displaying a punctated pattern throughout the cytoplasm. While quercetin inhibited ccHCV replication by more than 75% and 85% when cells were treated with 50μM-100μM respectively in comparison with untreated cells, it did not impact the entry of HCVpp. As well, quercetin decreased Core and NS3 protein level expression Conclusion: Quercetin has a major effect of LD morphology and interferes with HCV-induced steatosis. Besides, it decreases viral replication, core and NS3 proteins expression and

avoided the co-localization between core and lipid droplets, selleck chemical without impact on viral entry. Therefore, this flavonoid could be Buparlisib clinical trial considered as a new drug for hepatitis C treatment. Francesco Negro – Advisory

Committees or Review Panels: Roche, MSD, Gilead, Boehringer Ingelheim; Grant/Research Support: Roche, Gilead Manuel Romero-Gomez – Advisory Committees or Review Panels: Roche Farma, SA, MSD, SA, Janssen, SA., ABBOTT, SA; Grant/Research Support: Ferrer, SA The following people have nothing to disclose: Angela Rojas, Jose A. Del Campo, Marta Garda-Valdecasas, Sophie Clement In hepatitis C virus (HCV) infected patients, virions are associated with very low density lipoprotein (VLDL)-type lipoproteins forming an infectious lipo-viro-particle (LVP). Apolipoprotein E (apoE), a major component of VLDL, interacts with heparan sulfate proteoglycans (HSPG) at the hepatocyte cell surface. As well, apoE is present at the surface of the LVP playing a crucial role in HCV infectivity. We aimed to investigate the role of apoE and its functional regions in HCV infectivity and to identify the syndecan (Sdc) involved in the HCV entry process. First, using adenoviral vectors expressing wild type or mutant apoE, we complemented apoE expression in Huh7.5.1 depleted cells from the endogenous apoE. Increasing amounts of apoE lead

to a dose-dependent increase in HCV infectivity, the more apoE was expressed the more HCV particles were infectious, demonstrating the Tolmetin primary role of apoE in HCV infectivity. ApoE mutated in the HSPG binding domain (HSPG-BD) as well as competition experiment using a peptide mimicking the HSPGBD confirmed the HSPG dependency for HCV infectivity. Finally, silencing experiments targeting the HSPG syndecan (Sdc)1 or Sdc4 revealed that HCV entry was markedly decreased following Sdc4 silencing. This effect was not observed when HCV pseudoparticles entry was analyzed, confirming the essential role of apoE-Sdc interactions in HCV entry. Collectively, our data demonstrate that HCV-apoE-Sdc interactions mediate viral entry. Since viral entry has been shown to play a key role in acute liver graft infection and viral persistence, targeting apoE-Sdc interactions opens a new perspective to prevent HCV re-infection during transplantation and may provide novel therapeutic avenues.

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