{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:22:02Z","timestamp":1791836522353,"version":"4.3.4"},"reference-count":124,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["Project 5.704"],"award-info":[{"award-number":["Project 5.704"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU Hepatitis"],"award-info":[{"award-number":["TTU Hepatitis"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["Project 5.807"],"award-info":[{"award-number":["Project 5.807"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR179 (TP 15 & 18)"],"award-info":[{"award-number":["TRR179 (TP 15 & 18)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009781","name":"Australian Centre for HIV and Hepatitis Virology Research","doi-asserted-by":"publisher","award":["Annual grant"],"award-info":[{"award-number":["Annual grant"]}],"id":[{"id":"10.13039\/100009781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis B virus (HBV) is a globally-distributed pathogen and is a major cause of liver disease. HBV (or closely-related animal hepadnaviruses) can integrate into the host genome, but (unlike retroviruses) this integrated form is replication-defective. The specific role(s) of the integrated HBV DNA has been a long-standing topic of debate. Novel in vitro models of HBV infection combined with sensitive molecular assays now enable researchers to investigate this under-characterised phenomenon with greater ease and precision. This review covers the contributions these systems have made to understanding how HBV DNA integration induces liver cancer and facilitates viral persistence. We summarise the current findings into a working model of chronic HBV infection and discuss the clinical implications of this hypothetical framework on the upcoming therapeutic strategies used to curb HBV-associated pathogenesis.<\/jats:p>","DOI":"10.3390\/v13020180","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T08:29:16Z","timestamp":1611649756000},"page":"180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Hepatitis B Virus DNA Integration: In Vitro Models for Investigating Viral Pathogenesis and Persistence"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0482-4387","authenticated-orcid":false,"given":"Thomas","family":"Tu","sequence":"first","affiliation":[{"name":"Storr Liver Centre, Faculty of Medicine and Health, Westmead Clinical School and Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia"},{"name":"Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zhang","sequence":"additional","affiliation":[{"name":"Storr Liver Centre, Faculty of Medicine and Health, Westmead Clinical School and Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany"},{"name":"German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). 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