title: Statins can exert dual, concentration dependent effects on HCV entry in vitro.
abstract: Statins are used daily by a large and increasing number of individuals worldwide. They were initially designed as 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) inhibitors to treat patients with hypercholesterolemia. Recent studies on HCV chronically infected individuals have suggested that their use in vivo in combination with PEG-IFN and ribavirin favor the sustained viral response (SVR). Herein, we describe the effects of a set of statins on HCV entry and on HCV key entry factors in vitro. Our results suggest that all tested statins exert a proviral effect through the upregulation of LDLR. Interestingly, at higher concentration, we also provide evidence of a yet unknown competing antiviral effect of statins (except for pravastatin) through the downregulation of CLDN-1. Importantly, this work enlightens the blunt proviral effect of pravastatin at the entry step of HCV in vitro.
authors: INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Canada.
authors: Matthieu
authors: M
authors: Blanchet
authors: INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Canada.
authors: Quoc-Tuan
authors: QT
authors: Le
authors: Laboratory of Biochemical Neuroendocrinology, Institut de Recherches Cliniques de Montréal, Affiliated to the Université de Montréal, Montréal, Canada.
authors: Nabil G
authors: NG
authors: Seidah
authors: INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Canada. Electronic address: patrick.labonte@iaf.inrs.ca.
authors: Patrick
authors: P
authors: Labonté
mesh_terms: D062445:Claudin-1 / Q000378:metabolism; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D017035:Pravastatin / Q000009:adverse effects*; D011973:Receptors, LDL / Q000378:metabolism; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016898:Interferon-alpha; C573412:LDLR protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; C571406:PEG-IFN-SA; D011973:Receptors, LDL; D011092:Polyethylene Glycols; D012254:Ribavirin; D017035:Pravastatin
keywords: CD81; CLDN-1; Cholesterol; HCV; LDLR; Lipids; NPC1L1; PCSK9; Statins