Roles of the two distinct proteasome pathways in hepatitis C virus infection

Abstract

Hepatitis C virus (HCV) infection often causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The development of a HCV cell culture system enabled us to investigate its whole HCV life cycle and develop a better understanding of the pathogenesis of this virus. Post-translational modification plays a crucial role in HCV replication and in the maturation of viral particles. There is growing evidence also suggesting that the ubiquitin-proteasome pathway and the ubiquitin-independent proteasome pathway are involved in the stability control of HCV proteins. Many viruses are known to manipulate the proteasome pathways to modulate the cell cycle, inhibit apoptosis, evade the immune system, and activate cell signaling, thereby contributing to persistent infection and viral carcinogenesis. The identification of functional interactions between HCV and the proteasome pathways will therefore shed new light on the life cycle and pathogenesis of HCV. This review summarizes the current knowledge on the involvement of the ubiquitin-dependent and -independent proteasome pathways in HCV infection and discusses the roles of these two distinct mechanisms in HCV pathogenesis.