{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:58:07Z","timestamp":1770231487035,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada","award":["558342-2020"],"award-info":[{"award-number":["558342-2020"]}]},{"name":"Replicor Inc.","award":["558342-2020"],"award-info":[{"award-number":["558342-2020"]}]},{"DOI":"10.13039\/501100000038","name":"NSERC-Alliance","doi-asserted-by":"publisher","award":["558342-2020"],"award-info":[{"award-number":["558342-2020"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada Graduate Scholarship\u2014from the NSERC","award":["558342-2020"],"award-info":[{"award-number":["558342-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Individuals chronically infected with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) present an increased risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV mono-infected individuals. Although HDV only replicates in individuals coinfected or superinfected with HBV, there is currently no in vitro model that can stably express both viruses simultaneously, mimicking the chronic infections seen in HBV\/HDV patients. Here, we present the HepG2BD cell line as a novel in vitro culture system for long-term replication of HBV and HDV. HepG2BD cells derive from HepG2.2.15 cells in which a 2 kb HDV cDNA sequence was inserted into the adeno-associated virus safe harbor integration site 1 (AAVS1) using CRISPR-Cas9. A Tet-Off promoter was placed 5\u2032 of the genomic HDV sequence for reliable initiation\/repression of viral replication and secretion. HBV and HDV replication were then thoroughly characterized. Of note, non-dividing cells adopt a hepatocyte-like morphology associated with an increased production of both HDV and HBV virions. Finally, HDV seems to negatively interfere with HBV in this model system. Altogether, HepG2BD cells will be instrumental to evaluate, in vitro, the fundamental HBV\u2013HDV interplay during simultaneous chronic replication as well as for antivirals screening targeting both viruses.<\/jats:p>","DOI":"10.3390\/v16040532","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:44:52Z","timestamp":1711892692000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["HepG2BD: A Novel and Versatile Cell Line with Inducible HDV Replication and Constitutive HBV Expression"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3420-4374","authenticated-orcid":false,"given":"Matthieu","family":"Blanchet","sequence":"first","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"},{"name":"Replicor Inc., Montr\u00e9al, QC H4P 2R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2569-4323","authenticated-orcid":false,"given":"L\u00e9na","family":"Angelo","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmine","family":"T\u00e9treault","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Khabir","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0517-4646","authenticated-orcid":false,"given":"Camille","family":"Sureau","sequence":"additional","affiliation":[{"name":"INSERM U1259, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1433-0700","authenticated-orcid":false,"given":"Andrew","family":"Vaillant","sequence":"additional","affiliation":[{"name":"Replicor Inc., Montr\u00e9al, QC H4P 2R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Labont\u00e9","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1016\/0264-410X(90)90221-7","article-title":"Development and production aspects of a recombinant yeast-derived hepatitis B vaccine","volume":"8","author":"Stephenne","year":"1990","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study","volume":"3","year":"2018","journal-title":"Lancet Gastroenterol. 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