Impact of alcohol on hepatitis C virus replication and interferon signaling

Figure 1 Proposed model of hepatitis C virus (HCV)/alcohol interactions in hepatocytes. Metabolism of alcohol by cytochrome P450-2E1 (CYP2E1) and HCV replication leads to a synergistic induction of oxidative stress in the cell. Oxidative stress inhibits interferon (IFN)-α signalling and also leads to increased rates of inflammation, cirrhosis, and hepatocellular carcinoma (HCC). NS5A: Non-structural 5A; NF-κB: Nuclear factor κB; ROS: Reactive oxygen species.

Figure 2 IFN-α signal transduction. Binding of IFN-α to its cognate receptor on the cell surface results in activation of the Janus activated kinase (JAK)/STAT signaling pathway culminating in the production of interferon-stimulated genes (ISGs), many of which have anti-viral properties that act to limit HCV infection. Alcohol inhibits Y701, decreases interferon-stimulated response element (ISRE) activity, and subsequently dampens the ISG response.