Fig. 5

ROS activation and deactivation as a result of HBV. It has been reported that HBx disrupts the integrity of the outer mitochondrial membrane via interactions with that membrane. Furthermore, HBx binds to Voltage-dependent anion-selective channel protein 3 (VDAC3), modulating the permeability transition pore (PTP). The effect of HBx on PTP function was reported as an increase in cytoplasmic and mitochondrial Ca2+ concentrations. Inhibiting the expression of subunits of respiratory complexes I, II, IV, and V, HBx reduces the activity of the respiratory chain complex. A loss of mitochondrial membrane potential is the last stage in this chain of events, which might generate ROS. LHBs are retained and accumulated in the ER after overexpression, which is linked to ER stress and the activation of the UPR. Ca2+ release in the cytoplasm due to the UPR may initiate ROS production. Transcriptional activators include HBx and LHBs (if the PreS2-domain faces the cytoplasm). The activation of c-Raf, which was reported as essential for the HBV-dependent activation of Nrf2, is brought on by both regulatory proteins. Cytoprotective genes with an ARE sequence in their promoter begin to express with the HBV-dependent activation of Nrf2. ROS detoxification is made possible by the increased production of cytoprotective genes in HBV-expressing cells [85]