title: HBV DNA Integration: Molecular Mechanisms and Clinical Implications.
abstract: Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies.
authors.affiliation: Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany. thomas.tu@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tu
authors.affiliation: Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia. m.budzinska@centenary.org.au.|Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. m.budzinska@centenary.org.au.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Budzinska
authors.affiliation: Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia. n.shackel@unsw.edu.au.|Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. n.shackel@unsw.edu.au.|Liverpool Hospital, Gastroenterology, Sydney, NSW 2170, Australia. n.shackel@unsw.edu.au.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Shackel
authors.affiliation: Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany. Stephan.Urban@med.uni-heidelberg.de.|German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany. Stephan.Urban@med.uni-heidelberg.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Urban
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D011995:Recombination, Genetic; D016662:Virus Integration
chemical_list: D004279:DNA, Viral
keywords: hepatitis B virus; hepatocellular carcinoma; integration; non-homologous end joining; viral persistence