Variants in the human PPIA gene render host cells refractory to hepatitis C virus infection by destabilization of the essential host factor cyclophilin A

The hepatitis C virus (HCV), a world-wide leading cause of cirrhosis and liver cancer, utilizes a number of host encoded cofactors to infect and replicate in human hepatocytes. Among these, cyclophilin A (CypA) stands out because it is critical for viral replication and CypA inhibitors like alisporivir are currently the most advanced anti-HCV compounds with a host encoded target in clinical development. Several genetic variants in the PPIA gene encoding CypA have been described but their influence on the course of HCV infection is unknown. The aim of the present study was to determine the prevalence of coding no…