Subversion of cellular autophagy during virus infection: Insights from hepatitis B and hepatitis C viruses

Abstract

Autophagy is a self-eating process, in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment. Autophagy is generally thought of as a pro-survival mechanism which is not only important for balancing energy supply at times of nutrient deprivation but also in the removal of various stress stimuli to ensure homeostasis. In addition to the target materials of “self” origin, autophagy can also eliminate intracellular pathogens and acts as a defense mechanism to curb infections. In addition, autophagy is linked to the host cell's innate immune response. However, viruses have evolved various strategies to manipulate and overtake host cell machinery to establish productive replication and maintain infectious process. In fact, replication of many viruses has been found to be autophagy-dependent and suppression of autophagy can potentially affect the viral replication. Thus, autophagy can either serve as an anti-viral defense mechanism or a pro-viral process that supports viral replication. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are known to co-opt cellular autophagy process as a pro-viral tool. Both viruses also induce mitophagy, which contributes to the establishment of chronic hepatitis. This review focuses on the roles of autophagy and mitophagy in the chronic liver disease pathogenesis associated with HBV and HCV infections. Keywords: Autophagy, Hepatitis B virus (HBV), Hepatitis C virus (HCV), Endoplasmic reticulum (ER) stress, Mitophagy