NS5A and, to a lesser extent, NS5B and the core protein have been detected in autophagocytic vacuoles (Table S1 ). Whether the NS5A localization in the autophagosome observed in our study is a cellular defense mechanism elicited to degrade foreign antigens or a viral mediated self-preserving mechanism to enable viral replication remains to be determined. HCV transgenic mice expressing the full-length HCV polyprotein were also examined for the accumulation of autophagocytic vacuoles in the liver. However, no evidence of enhanced autophagy was detected. It is possible that additional factors are needed to cause the accumulation of autophagosomes in vivo or that very low viral protein expression levels in the transgenic mice were not sufficient to induce these changes. A previous study using the same line of transgenic mice [43] showed that long-term iron overload was necessary to induce the accumulation of autophagosomes. Since iron overload increases oxidative stress in the liver, the result is consistent with our finding in HCV protein-expressing cells in the relationship between oxidative stress and autophagy.