Hepatitis C virus infection, microRNA and liver disease progression

Abstract

Hepatitis C virus (HCV) is a global health problem with an estimated 170-200 million peoples (approximately 3% of world population) are chronically infected worldwide and new infections are predicted to be on rise in coming years. HCV infection remains categorized as a major risk factor for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. There has been considerable improvement in our understanding of virus life cycle since, the discovery of HCV two-decades ago. MicroRNAs (miRNAs) are important players in establishment of HCV infection and their propagation in infected hepatocytes. They target crucial host cellular factors needed for productive HCV replication and augmented cell growth. Very first anti-miRNA oligonucleotides, miravirsen has been tested in clinical trial and shown promising results as therapeutic agent in treatment against chronic HCV infection. Deregulated expression of miRNAs has been linked to the pathogenesis associated with HCV infection by controlling signaling pathways such as, proliferation, apoptosis and migration. Circulating miRNAs emerging as growing field in identification of biomarkers in disease progression and their potential as a means of communication between cells inside the liver is an exciting area of research in future. This review focuses on recent studies enforcing the contribution of miRNAs in HCV life cycle and coordinated regulation in HCV mediated liver disease progression.

Keywords: Hepatitis C virus; MicroRNA; Liver disease; Interferon signaling; Circulatory microRNA

Core tip: Hepatitis C virus (HCV) is the major cause of chronic liver disease that gradually progresses from chronic hepatitis to cirrhosis and hepatocellular carcinoma (HCC) during the course of infection. MicroRNAs (miRNAs) are small RNA molecules and have the ability to regulate gene expression by targeting mRNA degradation or translational repression. miRNAs regulate HCV life cycle either by supporting viral replication or by inhibiting interferon signaling pathway. Several miRNAs play important roles in HCV related inflammation, fibrosis and HCC development. This review focuses on the involvement of miRNA in HCV life cycle and virus mediated liver disease progression, emerging role of circulating miRNAs and exploitation of miRNA as alternative therapeutic approach for HCV infection.