Statins can exert dual, concentration dependent effects on HCV entry in vitro

• Statins exert dual effects on HCV entry (with the exception of pravastatin).
• Statins exert a proviral effect through induction of LDLR and likely NPC1L1.
• Statins exert an antiviral effect through the downregulation of CLDN-1 (with the exception of pravastatin).
• Pravastatin exerts a global proviral effect on HCV entry.

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.