{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:20Z","timestamp":1787028560319,"version":"build-2736575974"},"reference-count":149,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"National Agency of Research and Development (ANID): \u201cFinanciamiento Basal para Centros Cient\u00edficos y Tecnol\u00f3gicos de Excelencia Centro Ciencia &amp; Vida\u201d","doi-asserted-by":"publisher","award":["FB210008"],"award-info":[{"award-number":["FB210008"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"National Agency of Research and Development (ANID): \u201cFinanciamiento Basal para Centros Cient\u00edficos y Tecnol\u00f3gicos de Excelencia Centro Ciencia &amp; Vida\u201d","doi-asserted-by":"publisher","award":["FONDECYT 1240409"],"award-info":[{"award-number":["FONDECYT 1240409"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human viral infections remain a significant global health challenge, contributing to a substantial number of cancer cases worldwide. Among them, infections with oncoviruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are key drivers of hepatocellular carcinoma (HCC). Despite the availability of an effective HBV vaccine since the 1980s, millions remain chronically infected due to the persistence of covalently closed circular DNA (cccDNA) as a reservoir in hepatocytes. Current antiviral therapies, including nucleos(t)ide analogs and interferon, effectively suppress viral replication but fail to eliminate cccDNA, underscoring the urgent need for innovative therapeutic strategies. Direct-acting antiviral agents (DAAs), which have revolutionized HCV treatment with high cure rates, offer a promising model for HBV therapy. A particularly attractive target is the intrinsically disordered region (IDR) of the HBx protein, which regulates cccDNA transcription, viral replication, and oncogenesis by interacting with key host proteins. DAAs targeting these interactions could inhibit viral persistence, suppress oncogenic signaling, and overcome treatment resistance. This review highlights the potential of HBx-directed DAAs to complement existing therapies, offering renewed hope for a functional HBV cure and reduced cancer risk.<\/jats:p>","DOI":"10.3390\/ijms26083552","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T05:28:07Z","timestamp":1744262887000},"page":"3552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Intrinsically Disordered Region of HBx and Virus\u2013Host Interactions: Uncovering New Therapeutic Approaches for HBV and Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Rodrigo A.","family":"Villanueva","sequence":"first","affiliation":[{"name":"Centro Cient\u00edfico y Tecnol\u00f3gico de Excelencia Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Santiago 8580702, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-9436","authenticated-orcid":false,"given":"Alejandra","family":"Loyola","sequence":"additional","affiliation":[{"name":"Centro Cient\u00edfico y Tecnol\u00f3gico de Excelencia Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Santiago 8580702, Chile"},{"name":"Facultad de Ciencias, Universidad San Sebasti\u00e1n, Santiago 7510602, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1093\/clinids\/4.5.916","article-title":"A successful eradication campaign. Global eradication of smallpox","volume":"4","author":"Fenner","year":"1982","journal-title":"Rev. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1177\/0141076815605211","article-title":"Lessons from a modern review of the smallpox eradication files","volume":"108","author":"Metzger","year":"2015","journal-title":"J. R. Soc. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S1470-2045(12)70176-6","article-title":"Global burden of infection-related cancer revisited","volume":"13","author":"Danaei","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mui, U., Haley, C., and Tyring, S. (2017). Viral Oncology: Molecular Biology and Pathogenesis. J. Clin. Med., 6.","DOI":"10.3390\/jcm6120111"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2009.06.001","article-title":"The search for infectious causes of human cancers: Where and why","volume":"392","author":"Hausen","year":"2009","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S1470-2045(09)70096-8","article-title":"WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens\u2014Part B: Biological agents","volume":"10","author":"Bouvard","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Capasso, M., Cossiga, V., Guarino, M., Ranieri, L., and Morisco, F. (2024). The Role of Hepatitis Viruses as Drivers of Hepatocancerogenesis. Cancers, 16.","DOI":"10.3390\/cancers16081505"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Asandem, D., Segbefia, S., Kusi, K., and Bonney, J. (2024). Hepatitis B Virus Infection: A Mini Review. Viruses, 16.","DOI":"10.3390\/v16050724"},{"key":"ref_9","unstructured":"WHO (2021, June 15). Global Hepatitis Report, 2017. Available online: https:\/\/www.who.int\/hepatitis\/publications\/global-hepatitis-report2017\/en\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/s41575-020-0296-6","article-title":"The evolution and clinical impact of hepatitis B virus genome diversity","volume":"17","author":"Revill","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.virol.2015.02.031","article-title":"Molecular biology of hepatitis B virus infection","volume":"479\u2013480","author":"Seeger","year":"2015","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wei, L., and Ploss, A. (2021). Mechanism of Hepatitis B Virus cccDNA Formation. Viruses, 13.","DOI":"10.3390\/v13081463"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jhep.2016.01.027","article-title":"Overview of hepatitis B viral replication and genetic variability","volume":"64","author":"Tong","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.clinre.2020.04.018","article-title":"Hepatitis B virus American genotypes: Pathogenic variants?","volume":"44","author":"Pujol","year":"2020","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.3748\/wjg.v19.i33.5446","article-title":"HBV endemicity in Mexico is associated with HBV genotypes H and G","volume":"19","author":"Roman","year":"2013","journal-title":"World. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s00705-008-0231-6","article-title":"Prevalence of hepatitis B virus genotypes in chronic carriers in Santiago, Chile","volume":"153","author":"Venegas","year":"2008","journal-title":"Arch. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Villanueva, R., and Loyola, A. (2023). Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061674"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00049","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransportingpolypeptide is a functional receptor for human hepatitis B and D virus","volume":"1","author":"Yan","year":"2012","journal-title":"Elife"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Moreno, A., and Ploss, A. (2024). Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription. Viruses, 16.","DOI":"10.3390\/v16040609"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.antiviral.2017.11.015","article-title":"The diverse functions of the hepatitis B core\/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals","volume":"149","author":"Diab","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dias, J., Sarica, N., and Neuveut, C. (2021). Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation. Viruses, 13.","DOI":"10.3390\/v13050757"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bousali, M., Papatheodoridis, G., Paraskevis, D., and Karamitros, T. (2021). Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma. Microorganisms, 9.","DOI":"10.3390\/microorganisms9081787"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaan0241","DOI":"10.1126\/scitranslmed.aan0241","article-title":"RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg","volume":"9","author":"Wooddell","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Giosa, D., Lombardo, D., Musolino, C., Chines, V., Raffa, G., Tocco, F.C.d., D\u2019Aliberti, D., Caminiti, G., Saitta, C., and Alibrandi, A. (2023). Mitochondrial DNA is a target of HBV integration. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05017-4"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/hep.1840090226","article-title":"Compact organization of the hepatitis B virus genome","volume":"9","author":"Miller","year":"1989","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000024969","article-title":"Hepatitis B virus X protein: Structure, function and biology","volume":"42","author":"Murakami","year":"1999","journal-title":"Intervirology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1046\/j.1365-2893.2002.00381.x","article-title":"Regulatory elements of hepatitis B virus transcription","volume":"9","author":"Moolla","year":"2002","journal-title":"J. Viral Hepat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0042-6822(92)90163-J","article-title":"Characterization of the hepatitis B virus X- and nucleocapsid gene transcriptional regulatory elements","volume":"191","author":"Zhang","year":"1992","journal-title":"Virology"},{"key":"ref_29","first-page":"545","article-title":"Identification of a promoter element located upstream from the hepatitis B virus X gene","volume":"7","author":"Treinin","year":"1987","journal-title":"Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1128\/jvi.66.7.4382-4389.1992","article-title":"Alternate translation initiation on hepatitis B virus X mRNA produces multiple polypeptides that differentially transactivate class II and III promoters","volume":"66","author":"Kwee","year":"1992","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1046\/j.1440-1746.2003.02990.x","article-title":"Regulation of p21 and p27 expression by the hepatitis B virus X protein and the alternate initiation site X proteins, AUG2 and AUG3","volume":"18","author":"Leach","year":"2003","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/0006-291X(91)90379-L","article-title":"Full-length and truncated versions of the hepatitis B virus (HBV) X protein (pX) transactivate the cmyc protooncogene at the transcriptional level","volume":"176","author":"Balsano","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22593","DOI":"10.1016\/S0021-9258(17)31687-3","article-title":"Novel short transcripts of hepatitis B virus X gene derived from intragenic promoter","volume":"269","author":"Zheng","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s005350170027","article-title":"Hepatitis B virus X protein: A multifunctional viral regulator","volume":"36","author":"Murakami","year":"2001","journal-title":"J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, D., Hamadalnil, Y., and Tu, T. (2024). Hepatitis B Viral Protein HBx: Roles in Viral Replication and Hepatocarcinogenesis. Viruses, 16.","DOI":"10.3390\/v16091361"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"a021402","DOI":"10.1101\/cshperspect.a021402","article-title":"Hepatitis B Virus X and Regulation of Viral Gene Expression","volume":"6","author":"Slagle","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1128\/JVI.72.3.1737-1743.1998","article-title":"Cloning and characterization of a novel hepatitis B virus x binding protein that inhibits viral replication","volume":"72","author":"Melegari","year":"1998","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1126\/science.294.5550.2376","article-title":"Calcium signaling by HBx protein in hepatitis B virus DNA replication","volume":"294","author":"Bouchard","year":"2001","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1128\/JVI.79.7.4238-4245.2005","article-title":"Hepatitis B virus X protein stimulates viral genome replication via a DDB1-dependent pathway distinct from that leading to cell death","volume":"79","author":"Leupin","year":"2005","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1128\/JVI.02020-06","article-title":"Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo","volume":"81","author":"Keasler","year":"2007","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.jhep.2011.02.015","article-title":"Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection","volume":"55","author":"Lucifora","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.virol.2009.05.001","article-title":"Hepatitis B virus HBx protein localized to the nucleus restores HBx-deficient virus replication in HepG2 cells and in vivo in hydrodynamically-injected mice","volume":"390","author":"Keasler","year":"2009","journal-title":"Virology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19975","DOI":"10.1073\/pnas.0908365106","article-title":"Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function","volume":"106","author":"Belloni","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1128\/jvi.68.3.2026-2030.1994","article-title":"Woodchuck hepatitis virus X protein is required for viral infection in vivo","volume":"68","author":"Zoulim","year":"1994","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1172\/JCI200113787","article-title":"X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo","volume":"108","author":"Zhang","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/978-3-642-18932-6_12","article-title":"Hepatitis B Virus X Protein: Structure\u2013Function Relationships and Role in Viral Pathogenesis","volume":"Volume 166","author":"Kumar","year":"2004","journal-title":"Transcription Factors. Handbook of Experimental Pharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15118","DOI":"10.1016\/S0021-9258(17)36581-X","article-title":"Human hepatitis B virus X gene encodes a regulatory domain which represses transactivation of X protein","volume":"269","author":"Murakami","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/j.1349-7006.2006.00299.x","article-title":"Molecular functions and biological roles of hepatitis B virus x protein","volume":"97","author":"Tang","year":"2006","journal-title":"Cancer Sci."},{"key":"ref_49","first-page":"3566","article-title":"Hepatitis B virus X protein transcription activation domains are neither required nor sufficient for cell transformation","volume":"58","author":"Gottlob","year":"1998","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10059-012-0060-z","article-title":"Structural characterization of an intrinsically unfolded mini-HBX protein from hepatitis B virus","volume":"34","author":"Lee","year":"2012","journal-title":"Mol. Cells"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.virusres.2004.05.006","article-title":"The conserved amino-terminal region (amino acids 1\u201320) of the hepatitis B virus X protein shows a transrepression function","volume":"105","author":"Misra","year":"2004","journal-title":"Virus Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1073\/pnas.93.11.5647","article-title":"A truncated mutant (residues 58\u2013140) of the hepatitis B virus X protein retains transactivation function","volume":"93","author":"Kumar","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","first-page":"397","article-title":"Identification of three essential regions of hepatitis B virus X protein for trans-activation function","volume":"7","author":"Arii","year":"1992","journal-title":"Oncogene"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0014-5793(01)02773-9","article-title":"An internal segment (residues 58\u2013119) of the hepatitis B virus X protein is sufficient to activate MAP kinase pathways in mouse liver","volume":"504","author":"Nijhara","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1023\/A:1024491028647","article-title":"A carboxy-terminal region of the hepatitis B virus X protein promotes DNA interaction of CREB and mimics the native protein for transactivation function","volume":"26","author":"Reddi","year":"2003","journal-title":"Virus Genes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.virusres.2010.10.013","article-title":"The C-terminal region of the hepatitis B virus X protein is essential for its stability and function","volume":"155","author":"Lizzano","year":"2011","journal-title":"Virus Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1567-7249(01)00040-X","article-title":"Characterization of the mitochondrial association of hepatitis B virus X protein, HBx","volume":"1","author":"Huh","year":"2002","journal-title":"Mitochondrion"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12061","DOI":"10.1128\/JVI.00740-07","article-title":"Hepatitis B virus replication is associated with an HBx-dependent mitrochondrion-regulated increase in cytosolic calcium levels","volume":"81","author":"McClain","year":"2007","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e00248-19","DOI":"10.1128\/JVI.00248-19","article-title":"Spatiotemporal Analysis of Hepatitis B Virus X Protein in Primary Human Hepatocytes","volume":"93","author":"Kornyeyev","year":"2019","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e00250-19","DOI":"10.1128\/JVI.00250-19","article-title":"Hepatitis B Virus X Protein Function Requires Zinc Binding","volume":"93","author":"Ramakrishnan","year":"2019","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1038\/s41467-023-40225-w","article-title":"Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome","volume":"14","author":"Liu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.abb.2012.08.008","article-title":"Pro-apoptotic or anti-apoptotic property of X protein of hepatitis B virus is determined by phosphorylation at Ser31 by Akt","volume":"528","author":"Lee","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1750-9378-7-27","article-title":"The viral transactivator HBx protein exhibits a high potential for regulation via phosphorylation through an evolutionarily conserved mechanism","volume":"7","author":"Venegas","year":"2012","journal-title":"Infect. Agent. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Prieto, C., Montecinos, J., Jim\u00e9nez, G., Riquelme, C., Garrido, D., Hern\u00e1ndez, S., Loyola, A., and Villanueva, R. (2021). Phosphorylation of Phylogenetically Conserved Amino Acid Residues Confines HBx within Different Cell Compartments of Human Hepatocarcinoma Cells. Molecules, 26.","DOI":"10.3390\/molecules26051254"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nsmb.1719","article-title":"A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery","volume":"17","author":"Li","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9644","DOI":"10.1128\/JVI.00977-16","article-title":"DDB1 Stimulates Viral Transcription of Hepatitis B Virus via HBx-Independent Mechanisms","volume":"90","author":"Kim","year":"2016","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.bbrc.2014.06.042","article-title":"Structural characterization of the BH3-like motif of hepatitis B virus X protein","volume":"450","author":"Kusunoki","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1073\/pnas.1525616113","article-title":"Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx","volume":"113","author":"Jiang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5246","DOI":"10.1128\/jvi.70.8.5246-5254.1996","article-title":"Woodchuck hepatitis virus X protein is present in chronically infected woodchuck liver and woodchuck hepatocellular carcinomas which are permissive for viral replication","volume":"70","author":"Dandri","year":"1996","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1038\/sj.onc.1202867","article-title":"Hepatitis B virus X mutants, present in hepatocellular carcinoma tissue abrogate both the antiproliferative and transactivation effects of HBx","volume":"18","author":"Sirma","year":"1999","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/jmv.1067","article-title":"Subcellular localisation of the X protein in HBV infected hepatocytes","volume":"64","author":"Hoare","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1099\/0022-1317-82-4-871","article-title":"Intracellular localization of the hepatitis B virus HBx protein","volume":"82","author":"Henkler","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1099\/vir.0.009928-0","article-title":"Stimulation of hepatitis B virus genome replication by HBx is linked to both nuclear and cytoplasmic HBx expression","volume":"90","author":"Cha","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"25510","DOI":"10.1074\/jbc.273.39.25510","article-title":"HBx protein of hepatitis B virus activates Jak1-STAT signaling","volume":"273","author":"Lee","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Feitelson, M., Arzumanyan, A., Spector, I., and Medhat, A. (2022). Hepatitis B x (HBx) as a Component of a Functional Cure for Chronic Hepatitis B. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092210"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/jmv.1890360207","article-title":"Review: Hepatitis B virus X-gene product: A promiscuous transcriptional activator","volume":"36","author":"Rossner","year":"1992","journal-title":"J. Med. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7132","DOI":"10.1074\/jbc.272.11.7132","article-title":"Hepatitis B virus X protein is a transcriptional modulator that communicates with transcription factor IIB and the RNA polymerase II subunit 5","volume":"272","author":"Lin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.coviro.2018.01.007","article-title":"Role of HBx in hepatitis B virus persistence and its therapeutic implications","volume":"30","author":"Slagle","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nature17170","article-title":"Hepatitis B virus X protein identifies the Smc5\/6 complex as a host restriction factor","volume":"531","author":"Mueller","year":"2016","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wy\u017cewski, Z., \u015awitlik, W., Mielcarska, M., and Gregorczyk-Zboroch, K. (2021). The Role of Bcl-xL Protein in Viral Infections. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041956"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF01703079","article-title":"Hepatitis B Virus Genome Is Organized into Nucleosomes in the Nucleus of the Infected Cell","volume":"8","author":"Bock","year":"1994","journal-title":"Virus Genes."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1128\/jvi.69.6.3350-3357.1995","article-title":"The Covalently Closed Duplex Form of the Hepadnavirus Genome Exists In Situ as a Heterogeneous Population of Viral Minichromosomes","volume":"69","author":"Newbold","year":"1995","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e0136222","DOI":"10.1128\/jvi.01362-22","article-title":"Hepatitis B Virus Core Protein Is Not Required for Covalently Closed Circular DNA Transcriptional Regulation","volume":"96","author":"Zhong","year":"2022","journal-title":"J. Virol."},{"key":"ref_84","first-page":"341","article-title":"Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis","volume":"77","author":"Otsuka","year":"2023","journal-title":"Acta Med. Okayama"},{"key":"ref_85","first-page":"12","article-title":"Epigenetic mechanisms in hepatitis B virus-associated hepatocellular carcinoma","volume":"7","author":"Andrisani","year":"2021","journal-title":"Hepatoma Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.2147\/IDR.S240472","article-title":"cccDNA Maintenance in Chronic Hepatitis B\u2014Targeting the Matrix of Viral Replication","volume":"13","author":"Dandri","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1053\/j.gastro.2006.01.001","article-title":"Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones","volume":"130","author":"Pollicino","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Alarcon, V., Hern\u00e1ndez, S., Rubio, L., Alvarez, F., Flores, Y., Varas-Godoy, M., Ferrari, G.D., Kann, M., Villanueva, R., and Loyola, A. (2016). The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state. Sci. Rep., 6.","DOI":"10.1038\/srep25901"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.jhep.2015.06.023","article-title":"HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase","volume":"63","author":"Gerossier","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"100261","DOI":"10.1016\/j.aohep.2020.09.005","article-title":"The histone variant H3.3 regulates the transcription of the hepatitis B virus","volume":"21","author":"Garrido","year":"2021","journal-title":"Ann. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jcmgh.2022.05.007","article-title":"HIRA Supports Hepatitis B Virus Minichromosome Establishment and Transcriptional Activity in Infected Hepatocytes","volume":"14","author":"Locatelli","year":"2022","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e2085","DOI":"10.1002\/rmv.2085","article-title":"Histone deacetylases in virus-associated cancers","volume":"30","author":"Mirzaei","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1080\/22221751.2019.1666661","article-title":"Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation","volume":"8","author":"Chen","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"8362","DOI":"10.7150\/thno.57531","article-title":"HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver","volume":"11","author":"Yuan","year":"2021","journal-title":"Theranostics"},{"key":"ref_95","first-page":"161","article-title":"Intrinsic protein disorder in complete genomes","volume":"11","author":"Dunker","year":"2000","journal-title":"Genome Inform."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00018-014-1661-9","article-title":"Exceptionally abundant exceptions: Comprehensive characterization of intrinsic disorder in all domains of life","volume":"72","author":"Peng","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13260","DOI":"10.1073\/pnas.0906770106","article-title":"Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein","volume":"106","author":"Ferreon","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","first-page":"117","article-title":"Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion","volume":"141","author":"Ishiyama","year":"2010","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1515\/hsz-2011-0254","article-title":"Disorder-function relationships for the cell cycle regulatory proteins p21 and p27","volume":"393","author":"Mitrea","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Uversky, V. (2016). p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure-Function Continuum Concept. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111874"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.pbiomolbio.2008.05.007","article-title":"Intrinsic disorder in scaffold proteins: Getting more from less","volume":"98","author":"Cortese","year":"2008","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1111\/j.1742-4658.2005.04948.x","article-title":"Flexible nets. The roles of intrinsic disorder in protein interaction networks","volume":"272","author":"Dunker","year":"2005","journal-title":"FEBS J."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Khare, S., Chinchilla, P., and Baum, J. (2023). Multifaceted interactions mediated by intrinsically disordered regions play key roles in alpha synuclein aggregation. Curr. Opin. Struct. Biol., 80.","DOI":"10.1016\/j.sbi.2023.102579"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Damme, E.V., Vanhove, J., Severyn, B., Verschueren, L., and Pauwels, F. (2021). The Hepatitis B Virus Interactome: A Comprehensive Overview. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.724877"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0022-2836(02)00969-5","article-title":"Intrinsic disorder in cell-signaling and cancer-associated proteins","volume":"323","author":"Iakoucheva","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nsmb.1395","article-title":"In situ observation of protein phosphorylation by high-resolution NMR spectroscopy","volume":"15","author":"Selenko","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1007\/s00018-016-2299-6","article-title":"Mechanisms of viral mutation","volume":"73","year":"2016","journal-title":"Cell Mol. Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6880","DOI":"10.1021\/cr4005692","article-title":"Structural disorder in viral proteins","volume":"114","author":"Xue","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.tibs.2008.10.009","article-title":"Do viral proteins possess unique biophysical features?","volume":"34","author":"Tokuriki","year":"2009","journal-title":"Trends Biochem. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Dyson, H. (2023). Vital for Viruses: Intrinsically Disordered Proteins. J. Mol. Biol., 435.","DOI":"10.1016\/j.jmb.2022.167860"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Li, H., Yang, C., and Lo, S. (2021). Hepatitis C Viral Replication Complex. Viruses, 13.","DOI":"10.3390\/v13030520"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6457","DOI":"10.1128\/JVI.00008-09","article-title":"Intracellular localization of hepatitis delta virus proteins in the presence and absence of viral RNA accumulation","volume":"83","author":"Han","year":"2009","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.virol.2010.08.019","article-title":"Intrinsic disorder and oligomerization of the hepatitis delta virus antigen","volume":"407","author":"Alves","year":"2010","journal-title":"Virology"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Fusco, G., and Gianni, S. (2021). Function, Regulation, and Dysfunction of Intrinsically Disordered Proteins. Life, 11.","DOI":"10.3390\/life11020140"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2020.03.001","article-title":"Intrinsically disordered proteins of viruses: Involvement in the mechanism of cell regulation and pathogenesis","volume":"174","author":"Mishra","year":"2020","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.cbpa.2010.06.169","article-title":"Intrinsically disordered proteins are potential drug targets","volume":"14","author":"Metallo","year":"2010","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1517\/17460441.2016.1107041","article-title":"Targeting intrinsically disordered proteins in rational drug discovery","volume":"11","author":"Ambadipudi","year":"2016","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Kim, K. (2023). PPIases Par14\/Par17 Affect HBV Replication in Multiple Ways. Viruses, 15.","DOI":"10.3390\/v15020457"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e01840-18","DOI":"10.1128\/JVI.01840-18","article-title":"Parvulin 14 and Parvulin 17 Bind to HBx and cccDNA and Upregulate Hepatitis B Virus Replication from cccDNA to Virion in an HBx-Dependent Manner","volume":"93","author":"Saeed","year":"2019","journal-title":"J. Virol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4161\/cam.5.2.14773","article-title":"Cortactin: A multifunctional regulator of cellular invasiveness","volume":"5","author":"Kirkbride","year":"2011","journal-title":"Cell Adhes. Migr."},{"key":"ref_121","first-page":"143","article-title":"HBV X protein interacts with cytoskeletal signaling proteins through SH3 binding","volume":"2","author":"Feng","year":"2010","journal-title":"Front Biosci. (Elite Ed.)"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/s41419-019-1650-x","article-title":"The HBx-CTTN interaction promotes cell proliferation and migration of hepatocellular carcinoma via CREB1","volume":"10","author":"Li","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Obsilova, V., and Obsil, T. (2022). Structural insights into the functional roles of 14-3-3 proteins. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1016071"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1111\/jcmm.16490","article-title":"The role of 14-3-3 proteins in cell signalling pathways and virus infection","volume":"25","author":"Liu","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1002\/cam4.1512","article-title":"14-3-3\u03b6 binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma cells","volume":"7","author":"Tang","year":"2018","journal-title":"Cancer Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kiliti, A., Sharif, G., Martin, M., Wellstein, A., and Riegel, A. (2023). AIB1\/SRC-3\/NCOA3 function in estrogen receptor alpha positive breast cancer. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1250218"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3892\/ol.2012.803","article-title":"The role of AIB1 in breast cancer","volume":"4","author":"Chang","year":"2012","journal-title":"Oncol. Lett."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.bbrc.2012.05.021","article-title":"The interaction between hepatitis B virus X protein and AIB1 oncogene is required for the activation of NF\u03baB signal transduction","volume":"423","author":"Hong","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/hep.25751","article-title":"Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness","volume":"56","author":"Liu","year":"2012","journal-title":"Hepatology"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Kanna, M., Nakatsu, Y., Yamamotoya, T., Encinas, J., Ito, H., Okabe, T., Asano, T., and Sakaguchi, T. (2022). Roles of peptidyl prolyl isomerase Pin1 in viral propagation. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1005325"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Lee, Y., Teoh, D., Yeung, K., and Liou, Y. (2022). The kingdom of the prolyl-isomerase Pin1: The structural and functional convergence and divergence of Pin1. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.956071"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1053\/j.gastro.2006.12.030","article-title":"Pin1 interacts with a specific serine-proline motif of hepatitis B virus X-protein to enhance hepatocarcinogenesis","volume":"132","author":"Pang","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1053\/j.gastro.2007.06.033","article-title":"Pin1-HBx interaction: A step toward understanding the significance of hepatitis B virus genotypes in hepatocarcinogenesis","volume":"133","author":"Datta","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Chien, R., and Liaw, Y. (2022). Current Trend in Antiviral Therapy for Chronic Hepatitis B. Viruses, 14.","DOI":"10.3390\/v14020434"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Songtanin, B., Chaisrimaneepan, N., Mend\u00f3za, R., and Nugent, K. (2024). Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections. Viruses, 16.","DOI":"10.3390\/v16040618"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.cld.2023.05.005","article-title":"Are the New Nucleos(t)ide Analogs Better than the Old Nucleos(t)ide Analogs?","volume":"27","author":"Choi","year":"2023","journal-title":"Clin. Liver Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"105782","DOI":"10.1016\/j.antiviral.2023.105782","article-title":"Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy","volume":"221","author":"Zhao","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"593","DOI":"10.5009\/gnl240023","article-title":"Toward a Functional Cure for Hepatitis B","volume":"18","author":"Lok","year":"2024","journal-title":"Gut Liver"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.jhep.2021.11.024","article-title":"How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development?","volume":"76","author":"Wong","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"24066","DOI":"10.1021\/acsomega.2c02216","article-title":"HBV cccDNA-A Culprit and Stumbling Block for the Hepatitis B Virus Infection: Its Presence in Hepatocytes Perplexed the Possible Mission for a Functional Cure","volume":"7","author":"Bhat","year":"2022","journal-title":"ACS Omega"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11901-020-00534-w","article-title":"Targeting Viral cccDNA for Cure of Chronic Hepatitis B","volume":"19","author":"Ligat","year":"2020","journal-title":"Curr. Hepatol. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"110438","DOI":"10.1016\/j.virol.2025.110438","article-title":"HBx protein as a therapeutic target for functional cure of hepatitis B virus infection","volume":"604","author":"Kumar","year":"2025","journal-title":"Virology"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"He, W., Zheng, Z., Zhao, Q., Zhang, R., and Zheng, H. (2024). Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B. Pathogens, 13.","DOI":"10.3390\/pathogens13121100"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"S238","DOI":"10.1093\/cid\/ciad344","article-title":"Direct-Acting Antiviral Therapy for Treatment of Acute and Recent Hepatitis C Virus Infection: A Narrative Review","volume":"77","author":"Martinello","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"a037093","DOI":"10.1101\/cshperspect.a037093","article-title":"Hepatitis C Virus Replication","volume":"10","author":"Tabata","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_146","first-page":"0921","article-title":"Hepatitis C (chronic)","volume":"2015","author":"Yau","year":"2015","journal-title":"BMJ Clin. Evid."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Alazard-Dany, N., Denolly, S., Boson, B., and Cosset, F. (2019). Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets. Viruses, 11.","DOI":"10.3390\/v11010030"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.3748\/wjg.v29.i13.2015","article-title":"Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era","volume":"29","author":"Rzymski","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1080\/14656566.2024.2396024","article-title":"Cutting-edge pharmacotherapy for hepatitis C virus infection: A comprehensive review","volume":"25","author":"Liu","year":"2024","journal-title":"Expert. Opin. 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