{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:05:52Z","timestamp":1760144752414,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council of Taiwan","award":["110-2320-B-182-026","108-2320-B-182-019","CMRPD1M0151~2","CMRPD1M0751","CMRPG3H1521-3","CMRPG3M0361~3","BMRP278"],"award-info":[{"award-number":["110-2320-B-182-026","108-2320-B-182-019","CMRPD1M0151~2","CMRPD1M0751","CMRPG3H1521-3","CMRPG3M0361~3","BMRP278"]}]},{"name":"Chang Gung Memorial Hospital","award":["110-2320-B-182-026","108-2320-B-182-019","CMRPD1M0151~2","CMRPD1M0751","CMRPG3H1521-3","CMRPG3M0361~3","BMRP278"],"award-info":[{"award-number":["110-2320-B-182-026","108-2320-B-182-019","CMRPD1M0151~2","CMRPD1M0751","CMRPG3H1521-3","CMRPG3M0361~3","BMRP278"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV\u2019s involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan\u2019s National Health Research Institutes, 2.7% (8\/300) tested anti-HDV positive, with 62.7% (5\/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2\/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial\u2013mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.<\/jats:p>","DOI":"10.3390\/v16060817","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T11:03:47Z","timestamp":1716375827000},"page":"817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the Genetic Diversity of Hepatitis Delta Virus in Hepatocellular Carcinoma (HCC): Impact on Viral Evolution and Oncogenesis in HCC"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-8253","authenticated-orcid":false,"given":"Horng-Heng","family":"Juang","sequence":"first","affiliation":[{"name":"Department of Anatomy, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Liver Research Center, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan"},{"name":"School of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Shuo","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan-Bei","family":"Iang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Division of Microbiology, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4295-6062","authenticated-orcid":false,"given":"Yang-Hsiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Liver Research Center, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2143-0531","authenticated-orcid":false,"given":"Mei","family":"Chao","sequence":"additional","affiliation":[{"name":"Liver Research Center, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan"},{"name":"Department of Microbiology and Immunology and Division of Microbiology, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6124","DOI":"10.1073\/pnas.77.10.6124","article-title":"Delta Agent: Association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees","volume":"77","author":"Rizzetto","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00049","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus","volume":"1","author":"Yan","year":"2012","journal-title":"eLife"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/gutjnl-2018-316601","article-title":"Prevalence and burden of hepatitis D virus infection in the global population: A systematic review and meta-analysis","volume":"68","author":"Chen","year":"2019","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1093\/infdis\/jiz633","article-title":"Estimating the global prevalence, disease progression, and clinical outcome of hepatitis delta virus infection","volume":"221","author":"Miao","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jhep.2020.04.008","article-title":"The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis","volume":"73","author":"Stockdale","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_6","unstructured":"Polaris Observatory Collaborators (2024). Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories. J. Hepatol., 80, 232\u2013242."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jhep.2020.02.030","article-title":"Chronic hepatitis D and hepatocellular carcinoma: A systematic review and meta-analysis of observational studies","volume":"73","author":"Alfaiate","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1111\/jvh.13577","article-title":"Risk of hepatocellular carcinoma in hepatitis B and D virus co-infected patients: A systematic review and meta-analysis of longitudinal studies","volume":"28","author":"Kamal","year":"2021","journal-title":"J. Viral Hepat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7951","DOI":"10.1128\/JVI.79.13.7951-7958.2005","article-title":"RNA replication without RNA-dependent RNA polymerase: Surprises from hepatitis delta virus","volume":"79","author":"Lai","year":"2005","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1055\/s-0032-1323623","article-title":"Virology of hepatitis D virus","volume":"32","author":"Taylor","year":"2012","journal-title":"Semin. Liver Dis."},{"key":"ref_12","first-page":"123","article-title":"Control of ADAR1 editing of hepatitis delta virus RNAs","volume":"353","author":"Casey","year":"2012","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1128\/jvi.63.5.1945-1950.1989","article-title":"Initiation of replication of the human hepatitis delta virus genome from cloned DNA: Role of delta antigen","volume":"63","author":"Kuo","year":"1989","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1073\/pnas.88.19.8490","article-title":"The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus","volume":"88","author":"Chang","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Goodrum, G., and Pelchat, M. (2018). Insight into the contribution and disruption of host processes during HDV replication. Viruses, 11.","DOI":"10.3390\/v11010021"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liang, Y.J., Sun, C.P., Hsu, Y.C., Chen, Y.W., Wang, I.A., Su, C.W., Tao, M.H., and Wu, J.C. (2020). Statin inhibits large hepatitis delta antigen-Smad3-twist-mediated epithelial-to-mesenchymal transition and hepatitis D virus secretion. J. Biomed. Sci., 27.","DOI":"10.1186\/s12929-020-00659-6"},{"key":"ref_17","first-page":"151","article-title":"Hepatitis delta virus genetic variability: From genotypes I, II, III to eight major clades?","volume":"307","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1002\/hep.29574","article-title":"Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2152 clinical strains","volume":"66","author":"Brichler","year":"2017","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9016","DOI":"10.1073\/pnas.90.19.9016","article-title":"A genotype of hepatitis D virus that occurs in northern South America","volume":"90","author":"Casey","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1053\/j.gastro.2006.01.035","article-title":"Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients","volume":"130","author":"Su","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bahoussi, A.N., Wang, P.H., Guo, Y.Y., Rabbani, N., Wu, C., and Xing, L. (2022). Global distribution and natural recombination of hepatitis D virus: Implication of Kyrgyzstan emerging HDVs in the clinical outcomes. Viruses, 14.","DOI":"10.3390\/v14071467"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1128\/JVI.79.4.2221-2229.2005","article-title":"RNA recombination of hepatitis delta virus in natural mixed-genotype infection and transfected cultured cells","volume":"79","author":"Wang","year":"2005","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/jvh.12228","article-title":"Identification of a natural intergenotypic recombinant hepatitis delta virus genotype 1 and 2 in Vietnamese HBsAg-positive patients","volume":"22","author":"Sy","year":"2015","journal-title":"J. Viral Hepat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.jmii.2015.10.013","article-title":"RNA recombination in Hepatitis delta virus: Identification of a novel naturally occurring recombinant","volume":"50","author":"Lin","year":"2017","journal-title":"J. Microbiol. Immunol. Infect. Wei Mian Yu Gan Ran Za Zhi"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/jvh.13010","article-title":"Recombinant identification, molecular classification and proposed reference genomes for hepatitis delta virus","volume":"26","author":"Miao","year":"2019","journal-title":"J. Viral Hepat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12985-020-01355-5","article-title":"Performance of commercially available anti-HDV enzyme-linked immunosorbent assays in Taiwan","volume":"17","author":"Lin","year":"2020","journal-title":"Virol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199239","DOI":"10.1016\/j.virusres.2023.199239","article-title":"Unbranched rod-like RNA is required for RNA editing of hepatitis delta virus genotype 2 and genotype 4","volume":"338","author":"Hsu","year":"2023","journal-title":"Virus Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"970","DOI":"10.2144\/00295bm08","article-title":"Generation of deletion and point mutations with one primer in a single cloning step","volume":"29","author":"Makarova","year":"2000","journal-title":"Biotechniques"},{"key":"ref_29","first-page":"3858","article-title":"Growth of human hepatoma cells lines with differentiated functions in chemically defined medium","volume":"42","author":"Nakabayashi","year":"1982","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1099\/jgv.0.000297","article-title":"Whole-genome analysis of genetic recombination of hepatitis delta virus: Molecular domain in delta antigen determining trans-activating efficiency","volume":"96","author":"Chao","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chiang, K.C., Chang, K.S., Hsu, S.Y., Sung, H.C., Feng, T.H., Chao, M., and Juang, H.H. (2020). Human heme oxygenase-1 induced by interleukin-6 via JAK\/STAT3 pathways is a tumor suppressor gene in hepatoma cells. Antioxidants, 9.","DOI":"10.3390\/antiox9030251"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0006-291X(03)00338-3","article-title":"Molecular cloning and expression of the hepatitis delta virus genotype IIb genome","volume":"303","author":"Wang","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chang, K.S., Chen, S.T., Sung, H.C., Hsu, S.Y., Lin, W.Y., Hou, C.P., Lin, Y.H., Feng, T.H., Tsui, K.H., and Juang, H.H. (2022). WNT1 inducible signaling pathway protein 1 is a stroma-specific secreting protein inducing a fibroblast contraction and carcinoma cell growth in the human prostate. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911437"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1096-9071(199606)49:2<145::AID-JMV12>3.0.CO;2-D","article-title":"Characterization of a new genotype II hepatitis delta virus from Taiwan","volume":"49","author":"Lee","year":"1996","journal-title":"J. Med. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/S0006-291X(03)01076-3","article-title":"Initiation of RNA replication of cloned Taiwan-3 isolate of hepatitis delta virus genotype II in cultured cells","volume":"306","author":"Lin","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"60841","DOI":"10.18632\/oncotarget.18339","article-title":"Analyses of a whole-genome inter-clade recombination map of hepatitis delta virus suggest a host polymerase-driven and viral RNA structure-promoted template-switching mechanism for viral RNA recombination","volume":"8","author":"Chao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.virusres.2014.08.011","article-title":"Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus","volume":"195","author":"Lin","year":"2015","journal-title":"Virus Res."},{"key":"ref_38","unstructured":"Rizzetto, M., and Smedile, A. (2019). Hepatitis D. Virology, Management and Methodology, Il Pensiero Scientifico."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1128\/jvi.64.7.3192-3198.1990","article-title":"Hepatitis delta virus genome replication: A polyadenylated mRNA for delta antigen","volume":"64","author":"Hsieh","year":"1990","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1128\/jvi.62.6.1855-1861.1988","article-title":"Molecular cloning of hepatitis delta virus RNA from an infected woodchuck liver: Sequence, structure, and applications","volume":"62","author":"Kuo","year":"1988","journal-title":"J. Virol."},{"key":"ref_41","first-page":"173","article-title":"Functional and clinical significance of hepatitis D virus genotype II infection","volume":"307","author":"Wu","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1128\/JCM.01154-10","article-title":"Molecular epidemiology of hepatitis D virus infection among injecting drug users with and without human immunodeficiency virus infection in Taiwan","volume":"49","author":"Chang","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/hep.27742","article-title":"Changing hepatitis D virus epidemiology in a hepatitis B virus endemic area with a national vaccination program","volume":"61","author":"Lin","year":"2015","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dziri, S., Rodriguez, C., Gerber, A., Brichler, S., Alloui, C., Roulot, D., D\u00e9ny, P., Pawlotsky, J.M., Gordien, E., and Le Gal, F. (2021). Variable in vivo hepatitis D virus (HDV) RNA editing rates according to the HDV genotype. Viruses, 13.","DOI":"10.3390\/v13081572"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/(SICI)1096-9071(199901)57:1<64::AID-JMV9>3.0.CO;2-W","article-title":"Mixed genotypes infection with hepatitis D virus","volume":"57","author":"Wu","year":"1999","journal-title":"J. Med. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1128\/JCM.40.8.3047-3049.2002","article-title":"Hepatitis D virus genotypes in intravenous drug users in taiwan: Decreasing prevalence and lack of correlation with hepatitis B virus genotypes","volume":"40","author":"Kao","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0140-6736(95)91558-3","article-title":"Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D","volume":"346","author":"Wu","year":"1995","journal-title":"Lancet"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6438","DOI":"10.1128\/jvi.65.12.6438-6446.1991","article-title":"Regulation of polyadenylation of hepatitis delta virus antigenomic RNA","volume":"65","author":"Hsieh","year":"1991","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1002\/jmv.24412","article-title":"Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D","volume":"88","author":"Fouad","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.virusres.2011.07.006","article-title":"Hepatitis delta virus genotype 8 infection in Northeast Brazil: Inheritance from African slaves?","volume":"160","author":"Barros","year":"2011","journal-title":"Virus Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/jvh.13899","article-title":"Epidemiology of hepatitis D virus infection in Europe: Is it vanishing?","volume":"31","author":"Demirel","year":"2024","journal-title":"J. Viral Hepat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jhep.2020.06.038","article-title":"Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta","volume":"73","author":"Roulot","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.jhep.2019.12.028","article-title":"Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1","volume":"72","author":"Spaan","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9044","DOI":"10.1128\/JVI.00130-12","article-title":"Hepatitis D virus isolates with low replication and epithelial-mesenchymal transition-inducing activity are associated with disease remission","volume":"86","author":"Shih","year":"2012","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.jhep.2021.03.025","article-title":"Assembly and infection efficacy of hepatitis B virus surface protein exchanges in 8 hepatitis D virus genotype isolates","volume":"75","author":"Wang","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"37311","DOI":"10.1074\/jbc.M002947200","article-title":"Large isoform of hepatitis delta antigen activates serum response factor-associated transcription","volume":"275","author":"Goto","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1053\/j.gastro.2006.10.038","article-title":"Large hepatitis delta antigen modulates transforming growth factor-beta signaling cascades: Implication of hepatitis delta virus-induced liver fibrosis","volume":"132","author":"Choi","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10059-009-0100-5","article-title":"Hepatitis delta virus large antigen sensitizes to TNF-alpha-induced NF-kappaB signaling","volume":"28","author":"Park","year":"2009","journal-title":"Mol. Cells"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1365-2893.2012.01597.x","article-title":"Large hepatitis delta antigen activates STAT-3 and NF-kappaB via oxidative stress","volume":"19","author":"Williams","year":"2012","journal-title":"J. Viral Hepat."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:46:00Z","timestamp":1760107560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["v16060817"],"URL":"https:\/\/doi.org\/10.3390\/v16060817","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2024,5,21]]}}}