{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:27:42Z","timestamp":1780478862058,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The intrahepatic cholangiocyte organoids (ICOs) model was evaluated for host differences in hepatitis B virus (HBV) infection, cellular responses, antiviral and immunomodulator responses. Twelve ICOs generated from liver resections and biopsies were assessed for metabolic markers and functional HBV entry receptor expression throughout differentiation. Structural changes relevant to HBV infection were characterized using histology, confocal, and electron microscopy examinations. Optimal ICO culture conditions for HBV infection using HepAD38 (genotype D) and plasma\u2010derived HBV (genotype B and C) were described. HBV infection was confirmed using HBcAg immunostaining, qRT\u2010PCR (RNA, covalently closed circular DNA [cccDNA], extracellular DNA) and ELISA (HBsAg and HBeAg). Drug response to antiviral and immunosuppressive agent, and cellular responses (interferon\u2010stimulated genes [ISG]) to interferon\u2010\u03b1 and viral mimic (PolyI:C) were assessed. ICOs underwent metabolic and structural remodeling following differentiation. Optimal HBV infection was achieved in well\u2010differentiated ICOs using spinoculation, with time and donor\u2010dependent increase in HBV RNA, cccDNA, extracellular DNA, HBeAg and HBsAg. Donor\u2010dependent drug responsiveness to entry inhibitor and JAK inhibitor was observed. Despite having a robust ISG response to interferon\u2010\u03b1 and PolyI:C, HBV infection in ICOs did not upregulate ISGs. Human ICOs support HBV infection and replication with donor\u2010dependent variation in viral dynamics and cellular responses. These features can be utilized for the development of personalized drug testing platform for antivirals.<\/jats:p>","DOI":"10.1002\/jmv.29232","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T22:44:13Z","timestamp":1701125053000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of hepatitis B virus infection and interhost cellular responses using intrahepatic cholangiocyte organoids"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-2922","authenticated-orcid":false,"given":"Chuan K.","family":"Lim","sequence":"first","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital Doherty Institute for Infection and Immunity Melbourne Victoria Australia"},{"name":"Department of Infectious Diseases, Doherty Institute of Infection and Immunity The University of Melbourne  Melbourne Victoria Australia"},{"name":"Research Centre for Infectious Diseases and Department of Molecular and Biomedical Science, School of Biological Sciences The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Romeo","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases and Department of Molecular and Biomedical Science, School of Biological Sciences The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang M.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Doherty Institute of Infection and Immunity The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin J.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N.","family":"Kirby","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases and Department of Molecular and Biomedical Science, School of Biological Sciences The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"McCartney","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Royal Adelaide Hospital  Adelaide Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Royal Adelaide Hospital  Adelaide Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Vincan","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital Doherty Institute for Infection and Immunity Melbourne Victoria Australia"},{"name":"Department of Infectious Diseases, Doherty Institute of Infection and Immunity The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-1016","authenticated-orcid":false,"given":"Michael R.","family":"Beard","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases and Department of Molecular and Biomedical Science, School of Biological Sciences The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"1","volume-title":"Global Hepatitis Report","author":"WHO","year":"2017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29609"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06433-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313135"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.050"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60747"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4392"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.026"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05344-11"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04138-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2004.02.006"},{"key":"e_1_2_10_13_1","unstructured":"Babraham Institute.A Quality Control Tool for High Throughput Sequence Data. Babraham Institute; 2010. Accessed December 9 2019.http:\/\/www.bioinformatics.babraham.ac.uk?\/projects\/fastqc\/"},{"key":"e_1_2_10_14_1","volume-title":"ngsReports: An R Package for Managing FastQC Reports and Other NGS Related log Files","author":"Ward C","year":"2018"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2019.12.001"},{"key":"e_1_2_10_16_1","unstructured":"NCBI Homo sapiens Annotation Release 105; 2013. Accessed March 11 2020.https:\/\/www.ncbi.nlm.nih.gov\/genome\/annotation_euk\/Homo_sapiens\/105\/"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2017.04.003"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.8.3977-3983.2004"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412631111"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0241"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00191"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.04.030"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161313"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23525-w"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.04.020"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217433"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00091"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28780"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190366"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14863"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11826"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03540-12"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371692"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi051291x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.5114\/reum.2020.102006"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.825"},{"issue":"51","key":"e_1_2_10_41_1","first-page":"2280","article-title":"[Breakthrough in the treatment of chronic hepatitis C virus infections. Direct acting antivirals heals over 90 percent]","volume":"111","author":"Weiland O","year":"2014","journal-title":"Lakartidningen"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502677"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.07.014"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113019"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243462"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60220-8"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.01.044"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.29232","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:41:07Z","timestamp":1705138867000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.29232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/jmv.29232"],"URL":"https:\/\/doi.org\/10.1002\/jmv.29232","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"2023-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29232"}}