Cells respond to a variety of internal stress or cellular damages by forming autophagosomes to degrade damaged components and to recycle usable elements for future biosynthesis [33] . However, some RNA viruses, most notably, poliovirus, dengue virus, mouse hepatitis virus, and foot-and-mouth disease virus develop the abilities to overcome such cellular defense by hijacking the autophagocytic pathway to facilitate viral replication [34] [35] [36] [37] . Multiple studies in recent years have shown that HCV infection of the human hepatoma cell line Huh7 and immortalized human hepatocytes induce autophagocytic vacuoles [38, 39] and that autophagy machinery is required for the initiation of HCV replication [40] and the production of infectious particles [41] . HCV induces the accumulation of autophagosomes via activation of the unfolded protein response pathway without enhancing autophagocytic protein degradation [38, 42] . Consequently, inhibition of autophagy inhibits HCV replication [41] . Although most studies are carried out with HCV genotype 2a, it is now well accepted that autophagy probably also occurs with infection of other HCV genotypes. What is not clear from these studies is whether enhanced autophagy persists during the chronic phase of HCV infection, and if and to what extent oxidative stress contributes to HCV-mediated activation of autophagy. In this study, we observed the accumulation of autophagocytic vacuoles and up-regulation of the autophagosome marker, LC3, in the genome-length and subgenomic replicon cells (Figures 3B-3D) . The data suggests that HCV non-structural proteins play a role in inducing autophagy, possibly through ER stress ( Figure 1B) , mitochondrial damage ( Figures 1B and 2A) , and induction of oxidative stress (Figures 2D and 4B ). Core-on cells, on the other hand, had a slight increase in the number of autophagocytic vacuoles without a significant increase in LC3-II or total LC3 levels ( Figures 3B-3D) .