fig3

Figure 3. Mechanism of the earliest HBV-hepatocyte and WHV–hepatocyte DNA integration by non-homologous end joining: (A) Within 15 min upon HBV entry into hepatocytes via sodium NTCP receptor, ROS and iNOS are produced which shear cellular DNA within the nucleus. With simultaneous entry of the dsl HBV DNA into the nucleus, the NHEJ host DNA repair machinery is activated; (B) PARP, a host DNA repair enzyme, is triggered in response to host DNA breakage, and, while performing its host DNA repair function, it also binds to viral dsl-DNA and forms a complex with the host DNA, which is further joined by XRCC. Since host DNA shearing is mediated by oxidative stress, OGG is also involved in repair; (C) The coordinated DNA repair action results in fusion of viral DNA fragment with host DNA sequence, creating virus-host junction within hepatocyte nucleus. HBV: hepatitis B virus; WHV: woodchuck hepatitis virus; NTCP: taurocholate co-transporting polypeptide; ROS: reactive oxygen species; iNOS: inducible nitric oxide; dsl: double-stranded linear; NHEJ: non-homologous end joining; PARP1: Poly(ADP-ribose) polymerase 1; XRCC1: X-ray repair cross-complementing protein 1; OGG: 8-oxyguanidine DNA glucose.