{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:37:26Z","timestamp":1786541846298,"version":"build-2736575974"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2109"],"award-info":[{"award-number":["JPMJSP2109"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24fk0310506h0003, 25fk0310526h0001"],"award-info":[{"award-number":["24fk0310506h0003, 25fk0310526h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24fk0310506s0203, 25fk0310526s0301, 24zf0127008s0303, 25jm0210107h0003, 25ama221542h0001"],"award-info":[{"award-number":["24fk0310506s0203, 25fk0310526s0301, 24zf0127008s0303, 25jm0210107h0003, 25ama221542h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008529","name":"Chiba University","doi-asserted-by":"publisher","award":["IAAR Research Support Program"],"award-info":[{"award-number":["IAAR Research Support Program"]}],"id":[{"id":"10.13039\/501100008529","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-54083-1","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:25:06Z","timestamp":1780410306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stable state of hepatocyte chromatin during hepatitis B virus infection"],"prefix":"10.1038","volume":"16","author":[{"given":"Daichi","family":"Komiyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Okabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotake","family":"Kasai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Fukuyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahityar","family":"Rahmutulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Moriishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"54083_CR1","unstructured":"World Health Organization global. hepatitis report 2024: action for access in low- and middle-income countries. Global report, (2024)."},{"key":"54083_CR2","doi-asserted-by":"publisher","first-page":"18035","DOI":"10.1038\/nrdp.2018.35","volume":"4","author":"MF Yuen","year":"2018","unstructured":"Yuen, M. F. et al. Hepatitis B virus infection. Nat. Rev. Dis. Primers. 4, 18035 (2018).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"54083_CR3","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/286535a0","volume":"286","author":"JC Edman","year":"1980","unstructured":"Edman, J. C., Gray, P., Valenzuela, P., Rall, L. B. & Rutter, W. J. Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature 286, 535\u2013538 (1980).","journal-title":"Nature"},{"key":"54083_CR4","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/ng.2295","volume":"44","author":"WK Sung","year":"2012","unstructured":"Sung, W. K. et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat. Genet. 44, 765\u2013769 (2012).","journal-title":"Nat. Genet."},{"key":"54083_CR5","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1038\/ng.3126","volume":"46","author":"Y Totoki","year":"2014","unstructured":"Totoki, Y. et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat. Genet. 46, 1267\u20131273 (2014).","journal-title":"Nat. Genet."},{"key":"54083_CR6","doi-asserted-by":"publisher","first-page":"12992","DOI":"10.1038\/ncomms12992","volume":"7","author":"LH Zhao","year":"2016","unstructured":"Zhao, L. H. et al. Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma. Nat. Commun. 7, 12992 (2016).","journal-title":"Nat. Commun."},{"key":"54083_CR7","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.jhep.2011.02.015","volume":"55","author":"J Lucifora","year":"2011","unstructured":"Lucifora, J. et al. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. J. Hepatol. 55, 996\u20131003 (2011).","journal-title":"J. Hepatol."},{"key":"54083_CR8","doi-asserted-by":"publisher","first-page":"5061","DOI":"10.1158\/1078-0432.CCR-07-5082","volume":"14","author":"NF Ma","year":"2008","unstructured":"Ma, N. F. et al. COOH-terminal truncated HBV X protein plays key role in hepatocarcinogenesis. Clin. Cancer Res. 14, 5061\u20135068 (2008).","journal-title":"Clin. Cancer Res."},{"key":"54083_CR9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/hep.25979","volume":"57","author":"KM Sze","year":"2013","unstructured":"Sze, K. M., Chu, G. K., Lee, J. M. & Ng, I. O. C-terminal truncated hepatitis B virus x protein is associated with metastasis and enhances invasiveness by C-Jun\/matrix metalloproteinase protein 10 activation in hepatocellular carcinoma. Hepatology 57, 131\u2013139 (2013).","journal-title":"Hepatology"},{"key":"54083_CR10","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jhep.2021.08.010","volume":"76","author":"K Sekiba","year":"2022","unstructured":"Sekiba, K. et al. HBx-induced degradation of Smc5\/6 complex impairs homologous recombination-mediated repair of damaged DNA. J. Hepatol. 76, 53\u201362 (2022).","journal-title":"J. Hepatol."},{"key":"54083_CR11","doi-asserted-by":"publisher","first-page":"9369","DOI":"10.1128\/JVI.79.15.9369-9380.2005","volume":"79","author":"SF Wieland","year":"2005","unstructured":"Wieland, S. F. & Chisari, F. V. Stealth and cunning: hepatitis B and hepatitis C viruses. J. Virol. 79, 9369\u20139380 (2005).","journal-title":"J. Virol."},{"key":"54083_CR12","doi-asserted-by":"publisher","first-page":"6669","DOI":"10.1073\/pnas.0401771101","volume":"101","author":"S Wieland","year":"2004","unstructured":"Wieland, S., Thimme, R., Purcell, R. H. & Chisari, F. V. Genomic analysis of the host response to hepatitis B virus infection. Proc. Natl. Acad. Sci. U S A. 101, 6669\u20136674 (2004).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"54083_CR13","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1136\/gutjnl-2015-309809","volume":"64","author":"MHBV Nassal","year":"2015","unstructured":"Nassal, M. H. B. V. cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut 64, 1972\u20131984 (2015).","journal-title":"Gut"},{"key":"54083_CR14","doi-asserted-by":"crossref","unstructured":"Wei, L. & Ploss, A. Mechanism of Hepatitis B Virus cccDNA Formation. Viruses 13 (2021).","DOI":"10.3390\/v13081463"},{"key":"54083_CR15","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1053\/j.gastro.2003.10.048","volume":"126","author":"T Pollicino","year":"2004","unstructured":"Pollicino, T. et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology 126, 102\u2013110 (2004).","journal-title":"Gastroenterology"},{"key":"54083_CR16","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.jhep.2016.08.022","volume":"66","author":"CL Lai","year":"2017","unstructured":"Lai, C. L. et al. Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B. J. Hepatol. 66, 275\u2013281 (2017).","journal-title":"J. Hepatol."},{"key":"54083_CR17","doi-asserted-by":"crossref","unstructured":"Pietropaolo, V., Prezioso, C. & Moens, U. Role of Virus-Induced Host Cell Epigenetic Changes in Cancer. Int J. Mol. Sci 22 (2021).","DOI":"10.3390\/ijms22158346"},{"key":"54083_CR18","doi-asserted-by":"publisher","first-page":"1280210","DOI":"10.3389\/fmicb.2023.1280210","volume":"14","author":"J Minarovits","year":"2023","unstructured":"Minarovits, J. Human tumor viruses: induction of three-dimensional alterations in the host genome structure. Front. Microbiol. 14, 1280210 (2023).","journal-title":"Front. Microbiol."},{"key":"54083_CR19","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s12276-024-01207-0","volume":"56","author":"KD Kim","year":"2024","unstructured":"Kim, K. D. & Lieberman, P. M. Viral remodeling of the 4D nucleome. Exp. Mol. Med. 56, 799\u2013808 (2024).","journal-title":"Exp. Mol. Med."},{"key":"54083_CR20","doi-asserted-by":"publisher","first-page":"5313","DOI":"10.1038\/s41467-025-60534-6","volume":"16","author":"E Gonz\u00e1lez-Almela","year":"2025","unstructured":"Gonz\u00e1lez-Almela, E. et al. Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking. Nat. Commun. 16, 5313 (2025).","journal-title":"Nat. Commun."},{"key":"54083_CR21","doi-asserted-by":"publisher","first-page":"12840","DOI":"10.1128\/JVI.79.20.12840-12851.2005","volume":"79","author":"M Simpson-Holley","year":"2005","unstructured":"Simpson-Holley, M., Colgrove, R. C., Nalepa, G., Harper, J. W. & Knipe, D. M. Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection. J. Virol. 79, 12840\u201312851 (2005).","journal-title":"J. Virol."},{"key":"54083_CR22","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/s41588-020-0665-7","volume":"52","author":"A Okabe","year":"2020","unstructured":"Okabe, A. et al. Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma. Nat. Genet. 52, 919\u2013930 (2020).","journal-title":"Nat. Genet."},{"key":"54083_CR23","doi-asserted-by":"publisher","first-page":"105057","DOI":"10.1016\/j.ebiom.2024.105057","volume":"102","author":"H Mizokami","year":"2024","unstructured":"Mizokami, H. et al. Enhancer infestation drives tumorigenic activation of inactive B compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma. EBioMedicine 102, 105057 (2024).","journal-title":"EBioMedicine"},{"key":"54083_CR24","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.cell.2022.01.024","volume":"185","author":"M Zazhytska","year":"2022","unstructured":"Zazhytska, M. et al. Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia. Cell 185, 1052\u20131064e1012 (2022).","journal-title":"Cell"},{"key":"54083_CR25","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41564-023-01344-8","volume":"8","author":"R Wang","year":"2023","unstructured":"Wang, R. et al. SARS-CoV-2 restructures host chromatin architecture. Nat. Microbiol. 8, 679\u2013694 (2023).","journal-title":"Nat. Microbiol."},{"key":"54083_CR26","doi-asserted-by":"publisher","first-page":"4268","DOI":"10.1038\/s41467-018-06739-4","volume":"9","author":"P Moreau","year":"2018","unstructured":"Moreau, P. et al. Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin. Nat. Commun. 9, 4268 (2018).","journal-title":"Nat. Commun."},{"key":"54083_CR27","first-page":"e13274","volume":"23","author":"V D\u2019Arienzo","year":"2021","unstructured":"D\u2019Arienzo, V. et al. The CCCTC-binding factor CTCF represses hepatitis B virus enhancer I and regulates viral transcription. Cell. Microbiol. 23, e13274 (2021).","journal-title":"Cell. Microbiol."},{"key":"54083_CR28","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1080\/22221751.2020.1840311","volume":"9","author":"C Shen","year":"2020","unstructured":"Shen, C. et al. Yin-Yang 1 and HBx protein activate HBV transcription by mediating the spatial interaction of cccDNA minichromosome with cellular chromosome 19p13.11. Emerg. Microbes Infect. 9, 2455\u20132464 (2020).","journal-title":"Emerg. Microbes Infect."},{"key":"54083_CR29","doi-asserted-by":"publisher","first-page":"100330","DOI":"10.1016\/j.jhepr.2021.100330","volume":"3","author":"J Lucifora","year":"2021","unstructured":"Lucifora, J. et al. Evidence for long-term association of virion-delivered HBV core protein with cccDNA independently of viral protein production. JHEP Rep. 3, 100330 (2021).","journal-title":"JHEP Rep."},{"key":"54083_CR30","doi-asserted-by":"publisher","first-page":"109288","DOI":"10.1016\/j.celrep.2021.109288","volume":"35","author":"D Tang","year":"2021","unstructured":"Tang, D. et al. Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection. Cell. Rep. 35, 109288 (2021).","journal-title":"Cell. Rep."},{"key":"54083_CR31","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.bbrc.2013.12.052","volume":"443","author":"M Iwamoto","year":"2014","unstructured":"Iwamoto, M. et al. Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem. Biophys. Res. Commun. 443, 808\u2013813 (2014).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"54083_CR32","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.bbrc.2014.08.029","volume":"452","author":"N Ogura","year":"2014","unstructured":"Ogura, N., Watashi, K., Noguchi, T. & Wakita, T. Formation of covalently closed circular DNA in Hep38.7-Tet cells, a tetracycline inducible hepatitis B virus expression cell line. Biochem. Biophys. Res. Commun. 452, 315\u2013321 (2014).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"54083_CR33","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/B978-0-12-391938-0.00004-5","volume":"513","author":"HJ van de Werken","year":"2012","unstructured":"van de Werken, H. J. et al. 4\u00a0C technology: protocols and data analysis. Methods Enzymol. 513, 89\u2013112 (2012).","journal-title":"Methods Enzymol."},{"key":"54083_CR34","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ymeth.2019.07.014","volume":"170","author":"PHL Krijger","year":"2020","unstructured":"Krijger, P. H. L., Geeven, G., Bianchi, V., Hilvering, C. R. E. & de Laat W. 4\u00a0C-seq from beginning to end: A detailed protocol for sample preparation and data analysis. Methods 170, 17\u201332 (2020).","journal-title":"Methods"},{"key":"54083_CR35","doi-asserted-by":"publisher","first-page":"3333","DOI":"10.1093\/bioinformatics\/btw408","volume":"32","author":"M Cai","year":"2016","unstructured":"Cai, M., Gao, F., Lu, W. & Wang, K. w4CSeq: software and web application to analyze 4\u00a0C-seq data. Bioinformatics 32, 3333\u20133335 (2016).","journal-title":"Bioinformatics"},{"key":"54083_CR36","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbs017","volume":"14","author":"H Thorvaldsd\u00f3ttir","year":"2013","unstructured":"Thorvaldsd\u00f3ttir, H., Robinson, J. T. & Mesirov, J. P. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief. Bioinform. 14, 178\u2013192 (2013).","journal-title":"Brief. Bioinform"},{"key":"54083_CR37","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell. 38, 576\u2013589 (2010).","journal-title":"Mol. Cell."},{"key":"54083_CR38","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842 (2010).","journal-title":"Bioinformatics"},{"key":"54083_CR39","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1016\/j.cell.2014.11.021","volume":"159","author":"SS Rao","year":"2014","unstructured":"Rao, S. S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665\u20131680 (2014).","journal-title":"Cell"},{"key":"54083_CR40","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s13059-015-0831-x","volume":"16","author":"N Servant","year":"2015","unstructured":"Servant, N. et al. HiC-Pro: an optimized and flexible pipeline for Hi-C data processing. Genome Biol. 16, 259 (2015).","journal-title":"Genome Biol."},{"key":"54083_CR41","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.cels.2015.07.012","volume":"3","author":"NC Durand","year":"2016","unstructured":"Durand, N. C. et al. Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom. Cell. Syst. 3, 99\u2013101 (2016).","journal-title":"Cell. Syst."},{"key":"54083_CR42","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"54083_CR43","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","volume":"37","author":"D Kim","year":"2019","unstructured":"Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907\u2013915 (2019).","journal-title":"Nat. Biotechnol."},{"key":"54083_CR44","doi-asserted-by":"publisher","first-page":"W187","DOI":"10.1093\/nar\/gku365","volume":"42","author":"F Ram\u00edrez","year":"2014","unstructured":"Ram\u00edrez, F., D\u00fcndar, F., Diehl, S., Gr\u00fcning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187\u2013191 (2014).","journal-title":"Nucleic Acids Res."},{"key":"54083_CR45","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","volume":"12","author":"B Li","year":"2011","unstructured":"Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 12, 323 (2011).","journal-title":"BMC Bioinform."},{"key":"54083_CR46","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","volume":"14","author":"EY Chen","year":"2013","unstructured":"Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform. 14, 128 (2013).","journal-title":"BMC Bioinform."},{"key":"54083_CR47","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90\u201397 (2016).","journal-title":"Nucleic Acids Res."},{"key":"54083_CR48","doi-asserted-by":"publisher","first-page":"e1002359","DOI":"10.1371\/journal.pgen.1002359","volume":"7","author":"A Kaneda","year":"2011","unstructured":"Kaneda, A. et al. Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence. PLoS Genet. 7, e1002359 (2011).","journal-title":"PLoS Genet."},{"key":"54083_CR49","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods. 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"54083_CR50","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/S0002-9440(10)63352-4","volume":"165","author":"C Tateno","year":"2004","unstructured":"Tateno, C. et al. Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am. J. Pathol. 165, 901\u2013912 (2004).","journal-title":"Am. J. Pathol."},{"key":"54083_CR51","doi-asserted-by":"publisher","first-page":"539","DOI":"10.2133\/dmpk.DMPK-10-RG-047","volume":"25","author":"C Yamasaki","year":"2010","unstructured":"Yamasaki, C. et al. In vitro evaluation of cytochrome P450 and glucuronidation activities in hepatocytes isolated from liver-humanized mice. Drug Metab. Pharmacokinet. 25, 539\u2013550 (2010).","journal-title":"Drug Metab. Pharmacokinet."},{"key":"54083_CR52","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/j.ajpath.2015.01.028","volume":"185","author":"Y Ishida","year":"2015","unstructured":"Ishida, Y. et al. Novel robust in vitro hepatitis B virus infection model using fresh human hepatocytes isolated from humanized mice. Am. J. Pathol. 185, 1275\u20131285 (2015).","journal-title":"Am. J. Pathol."},{"key":"54083_CR53","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1038\/s41467-019-09982-5","volume":"10","author":"HS Kaya-Okur","year":"2019","unstructured":"Kaya-Okur, H. S. et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930 (2019).","journal-title":"Nat. Commun."},{"key":"54083_CR54","doi-asserted-by":"publisher","first-page":"2964","DOI":"10.1038\/s41467-025-57447-9","volume":"16","author":"T Nakagawa","year":"2025","unstructured":"Nakagawa, T. et al. Inhibition of human-HPV hybrid ecDNA enhancers reduces oncogene expression and tumor growth in oropharyngeal cancer. Nat. Commun. 16, 2964 (2025).","journal-title":"Nat. Commun."},{"key":"54083_CR55","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/j.jhep.2015.06.023","volume":"63","author":"L Rivi\u00e8re","year":"2015","unstructured":"Rivi\u00e8re, L. et al. HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase. J. Hepatol. 63, 1093\u20131102 (2015).","journal-title":"J. Hepatol."},{"key":"54083_CR56","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1016\/j.cell.2025.01.033","volume":"188","author":"NA Prescott","year":"2025","unstructured":"Prescott, N. A. et al. A nucleosome switch primes hepatitis B virus infection. Cell 188, 2111\u20132126e2121 (2025).","journal-title":"Cell"},{"key":"54083_CR57","doi-asserted-by":"publisher","first-page":"E5715","DOI":"10.1073\/pnas.1518090112","volume":"112","author":"P Tropberger","year":"2015","unstructured":"Tropberger, P. et al. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation. Proc. Natl. Acad. Sci. U S A. 112, E5715\u20135724 (2015).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"54083_CR58","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1126\/science.284.5415.825","volume":"284","author":"LG Guidotti","year":"1999","unstructured":"Guidotti, L. G. et al. Viral clearance without destruction of infected cells during acute HBV infection. Science 284, 825\u2013829 (1999).","journal-title":"Science"},{"key":"54083_CR59","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1128\/JVI.77.1.68-76.2003","volume":"77","author":"R Thimme","year":"2003","unstructured":"Thimme, R. et al. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J. Virol. 77, 68\u201376 (2003).","journal-title":"J. Virol."},{"key":"54083_CR60","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1053\/j.gastro.2018.01.034","volume":"154","author":"A Suslov","year":"2018","unstructured":"Suslov, A., Boldanova, T., Wang, X., Wieland, S. & Heim, M. H. Hepatitis B Virus Does Not Interfere With Innate Immune Responses in the Human Liver. Gastroenterology 154, 1778\u20131790 (2018).","journal-title":"Gastroenterology"},{"key":"54083_CR61","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1002\/hep.29348","volume":"66","author":"X Cheng","year":"2017","unstructured":"Cheng, X. et al. Hepatitis B virus evades innate immunity of hepatocytes but activates cytokine production by macrophages. Hepatology 66, 1779\u20131793 (2017).","journal-title":"Hepatology"},{"key":"54083_CR62","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/hep.25954","volume":"57","author":"SP Fletcher","year":"2013","unstructured":"Fletcher, S. P. et al. Identification of an intrahepatic transcriptional signature associated with self-limiting infection in the woodchuck model of hepatitis B. Hepatology 57, 13\u201322 (2013).","journal-title":"Hepatology"},{"key":"54083_CR63","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1002\/hep.20892","volume":"42","author":"M Tsuge","year":"2005","unstructured":"Tsuge, M. et al. Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus. Hepatology 42, 1046\u20131054 (2005).","journal-title":"Hepatology"},{"key":"54083_CR64","doi-asserted-by":"publisher","first-page":"e0142145","DOI":"10.1371\/journal.pone.0142145","volume":"10","author":"C Tateno","year":"2015","unstructured":"Tateno, C. et al. Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA\/SCID Mice. PLoS One. 10, e0142145 (2015).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54083-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54083-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54083-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:02:54Z","timestamp":1786539774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-54083-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["54083"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-54083-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"assertion":[{"value":"28 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"25085"}}