To address the pathogenesis caused by HCV infection, recent studies have begun to focus on direct cytopathic effects. HCV proteins associate with different subcellular structures, including mitochondria, endoplasmic reticulum (ER), and lipid droplets, to facilitate replication and assembly of viral particles [2] . These associations lead to alterations of the integrity and functions of organelles. HCV-mediated oxidative stress is commonly observed and is achieved by increasing reactive oxygen and nitrogen species (ROS and RNS) or by altering cellular antioxidant capacities [8] [9] [10] [11] . In particular, HCV core proteins are shown to be closely associated with the mitochondria and cause increases in ROS and RNS production and lipid peroxidation [11] [12] [13] [14] , reduction in GSH and NADPH concentrations, reduction in mitochondrial complex I activities, and increase in mitochondrial Ca +2 uptake, which ultimately disrupts mitochondrial membrane permeability and leads to mitochondrial dysfunction [14, 15] . HCV nonstructural proteins have also been implicated in disturbing the redox balance and altering antioxidant enzyme levels [16, 17] . Specifically, NS5A is shown to up-regulate Mn superoxide dismutase (MnSOD) through AP1 transcription factor in the p38 MAPK and JNK signaling pathways [18, 19] . Additional studies showed the involvement of NS5A in ER stress and disturbance of intracellular Ca +2 homeostasis, which leads to increased mitochondrial ROS production and altered mitochondrial function [18, 20] . Because of the relationship between chronic HCV infection and the development of hepatocellular carcinoma, studies have also been carried out to identify HCV proteins that may be responsible for the hepatocarcinogenesis. For example, the HCV core protein has been shown to promote immortalization of primary human hepatocytes [21] , whereas the non-structural proteins NS3 and NS4B have been shown to transform NIH 3T3 cells either individually or in combination with Ha-ras [22, 23] .