Perturbation of autophagic pathway by hepatitis C virus.

Autophagy removes long-lived proteins and damaged organelles and is important for maintaining cellular homeostasis. It can also serve in innate immunity to remove intracellular pathogens. As such, viruses have evolved different mechanisms to subvert this innate immune response. We have recently demonstrated that hepatitis C virus (HCV) can also suppress autophagic protein degradation by suppressing the fusion between autophagosomes and lysosomes. This suppression causes the accumulation of autophagosomes and enhances HCV RNA replication.(1) Our further analysis indicated that the induction of autophagosomes by HCV is dependent on the unfolded protein response (UPR). Our studies thus delineate a molecular pathway by which HCV induces autophagosomes. The prolonged perturbation of the autophagic pathway by HCV likely plays an important role in HCV pathogenesis.