Autophagy in hepatitis C virus-host interactions: Potential roles and therapeutic targets for liver-associated diseases

Abstract

Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis. Hepatitis C virus (HCV) is a major cause of chronic hepatitis, which often leads to end-stage liver-associated diseases and is a significant burden on worldwide public health. Emerging lines of evidence indicate that autophagy plays an important role in promoting the HCV life cycle in host cells. Moreover, the diverse impacts of autophagy on a variety of signaling pathways in HCV-infected cells suggest that the autophagic process is required for balancing HCV-host cell interactions and involved in the pathogenesis of HCV-related liver diseases. However, the detailed molecular mechanism underlying how HCV activates autophagy to benefit viral growth is still enigmatic. Additionally, how the autophagic response contributes to disease progression in HCV-infected cells remains largely unknown. Hence, in this review, we overview the interplay between autophagy and the HCV life cycle and propose possible mechanisms by which autophagy may promote the pathogenesis of HCV-associated chronic liver diseases. Moreover, we outline the related studies on how autophagy interplays with HCV replication and discuss the possible implications of autophagy and viral replication in the progression of HCV-induced liver diseases, e.g., steatosis and hepatocellular carcinoma. Finally, we explore the potential therapeutics that target autophagy to cure HCV infection and its related liver diseases.

Keywords: Autophagy, Hepatitis C virus, Steatosis, Cirrhosis, Hepatocellular carcinoma

Core tip: Hepatitis C virus (HCV) is a major cause of chronic liver disease and is associated with over 170 million infected individuals worldwide. However, a successful strategy for completely eradicating HCV infection is still limited. Autophagy is a catabolic process that delivers cytosolic components to lysosomes for breakdown. HCV has been shown to activate autophagy to promote viral growth in vitro. In this review, we outline the recent findings on the physiological significance of autophagy in the HCV life cycle and propose a potential role of autophagy in the development of HCV-related liver diseases as well as a perspective on therapeutics targeting autophagy to cure HCV infection.