Figure 7.

Schematic presentation indicating distinct mitochondrial stress mediated IFN-I production and its distinct contribution to disease progression in chronic patients with genotype C infections between rt269L and rt269I. In contrast to rt269L, rt269I infection in genotype C induced mitochondrial ROS production, which led to an increased release of oxidized DNA into the cytosols of the infected hepatocytes. Sensing the oxidized DNA exposed to cytosol via the cGAS-STING pathway could lead to IFN-I production. Enhanced INF-I production in rt269I could exert several biological activities. First, it can lead to the increased inhibition of HBV replication via the inhibition of capsid formation by HO-1 production. Second, IFN-I mediated enhanced expression of APOBEC3G and iNOS can lead to HBeAg negative infection and liver disease progression via frequent generation of preC mutations at 1896 (G to A). Thus, rt269L can contribute to HBeAg negative infection and disease progression in chronic patients infected with genotype C via mitochondrial stress mediated enhanced INF-I production.