Figure 2.

Role of HBV DNA integration in liver disease and HCC development. The HBV double-stranded linear DNA (dslDNA) obtained after the plus-strand DNA extension is completed is the main substrate for HBV DNA integration. HBV dslDNA can integrate into the host cell genome at the sites of cellular double-stranded DNA breaks by nonhomologous end joining (NHEJ) or microhomology-mediated end joining (MMEJ) repair pathways depending on the sequence characteristics at the ends of the viral DNA and the host double-stranded break DNA. Integration of HBV DNA sequences into the host genome as well as prolonged production of HBx and HBsAg and/or of modified forms of HBx and preS/S envelope proteins may contribute to viral infection persistence and to liver damage via multiple mechanisms, which ultimately lead to liver cancer development.