LRRFIP1 INHIBITS HEPATITIS C VIRUS REPLICATION BY INDUCING TYPE I INTERFERON IN HEPATOCYTES

Background: Hepatitis C virus infection is one of the leading causes of end stage liver diseases. The innate immune response slows down viral replication by activating cytokines such as type I interferon (IFN-alpha/beta), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. Recently, leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) was reported contributing to the production of interferon-beta in macrophages. Objectives: The aim of this study was to assess the role of LRRFIP1 in induction of IFN-beta and inhibition of HCV infection in hepatocytes. Materials and Methods: Induction of IFN-beta by LRRFIP1 in Huh7 and Huh7.5.1 was determined by real-time PCR and western blotting in vitro. Inhibition of HCV replication by LRRFIP1 overexpression in hepatocytes was assessed. Results: LRRFIP1 increased the expression of IFN-beta in hepatocytes with or without HCV infection. Induction of IFN-beta by LRRFIP1 was enhanced with the presence of hepatitis C virus. Overexpression of LRRFIP1 in hepatocytes inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1. Conclusions: LRRFIP1 and its mediated production of type I interferon play a role in controlling HCV infection. The findings of this study provide new target for HCV treatment and contribute to development of anti-HCV drugs.