{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:54:43Z","timestamp":1791248083507,"version":"4.1.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":87,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"2023 National Key R&D Program of China","award":["2023YFC2308100"],"award-info":[{"award-number":["2023YFC2308100"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"DOI":"10.1186\/s12985-026-03246-7","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:33:46Z","timestamp":1783740826000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RRM2B is associated with low-level viremia during entecavir therapy in pediatric chronic hepatitis B and promotes profibrotic signaling in vitro"],"prefix":"10.1186","volume":"23","author":[{"given":"Yuanzhen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoxue","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunan","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"issue":"2","key":"3246_CR1","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.jhep.2025.03.018","volume":"83","author":"AFTS European","year":"2025","unstructured":"European AFTS. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol. 2025;83(2):502\u201383.","journal-title":"J Hepatol"},{"issue":"26","key":"3246_CR2","doi-asserted-by":"publisher","first-page":"4182","DOI":"10.3748\/wjg.v27.i26.4182","volume":"27","author":"P Veronese","year":"2021","unstructured":"Veronese P, Dodi I, Esposito S, et al. Prevention of vertical transmission of hepatitis B virus infection[J]. World J Gastroenterol. 2021;27(26):4182\u201393.","journal-title":"World J Gastroenterol"},{"key":"3246_CR3","first-page":"101193","volume":"51","author":"Z Hui","year":"2024","unstructured":"Hui Z, Yu W, Fuzhen W, et al. New progress in HBV control and the cascade of health care for people living with HBV in China: evidence from the fourth national serological survey, 2020[J]. The Lancet regional health. Western Pac. 2024;51:101193.","journal-title":"Western Pac"},{"issue":"6","key":"3246_CR4","first-page":"1425","volume":"11","author":"H You","year":"2023","unstructured":"You H, Wang F, Li T, et al. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022)[J]. J Clin translational Hepatol. 2023;11(6):1425\u201342.","journal-title":"J Clin translational Hepatol"},{"key":"3246_CR5","doi-asserted-by":"publisher","first-page":"103400","DOI":"10.1016\/j.eclinm.2025.103400","volume":"87","author":"C Wang","year":"2025","unstructured":"Wang C, Kong F, Gao H, et al. Safety and efficacy of GST-HG141, a novel HBV capsid assembly modulator, for the treatment of chronic hepatitis B patients with low-level viremia: a randomized, double-blind, placebo-controlled, multicenter phase II study[J]. EClinicalMedicine. 2025;87:103400.","journal-title":"EClinicalMedicine"},{"issue":"6","key":"3246_CR6","first-page":"850","volume":"9","author":"Q Zhang","year":"2021","unstructured":"Zhang Q, Peng H, Liu X, et al. Chronic Hepatitis B Infection with Low Level Viremia Correlates with the Progression of the Liver Disease[J]. J Clin translational Hepatol. 2021;9(6):850\u20139.","journal-title":"J Clin translational Hepatol"},{"issue":"3","key":"3246_CR7","doi-asserted-by":"publisher","first-page":"195","DOI":"10.14218\/JCTH.2019.00047","volume":"7","author":"S Liu","year":"2019","unstructured":"Liu S, Xin Y. HBV cccDNA: The Stumbling Block for Treatment of HBV Infection[J]. J Clin translational Hepatol. 2019;7(3):195\u20136.","journal-title":"J Clin translational Hepatol"},{"issue":"1","key":"3246_CR8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3390\/biom15010062","volume":"15","author":"A Boonstra","year":"2025","unstructured":"Boonstra A, Sari G. HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication[J]. Biomolecules. 2025;15(1):62.","journal-title":"Biomolecules"},{"issue":"4","key":"3246_CR9","doi-asserted-by":"publisher","first-page":"gkag73","DOI":"10.1093\/nar\/gkag073","volume":"54","author":"D Huang","year":"2026","unstructured":"Huang D, Zheng Y, Deng E, et al. Chromatin remodeler BAF maintains HBV cccDNA transcriptional competence and represents a therapeutic target[J]. Nucleic Acids Res. 2026;54(4):gkag73.","journal-title":"Nucleic Acids Res"},{"key":"3246_CR10","doi-asserted-by":"crossref","unstructured":"Cheng X, Xia Y, Li C et al. A genome-wide siRNA screen identifies previously unknown proviral and antiviral host factors in HBV infection[J]. J Hepatol. 2026;84(5):874\u201386.","DOI":"10.1016\/j.jhep.2025.11.017"},{"issue":"2","key":"3246_CR11","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.cell.2025.11.031","volume":"189","author":"CN Tzouanas","year":"2026","unstructured":"Tzouanas CN, Shay JES, Sherman MS, et al. Hepatic adaptation to chronic metabolic stress primes tumorigenesis[J]. Cell. 2026;189(2):435\u201360.","journal-title":"Cell"},{"issue":"3","key":"3246_CR12","doi-asserted-by":"publisher","first-page":"841","DOI":"10.3350\/cmh.2024.0694","volume":"31","author":"S Cheng","year":"2025","unstructured":"Cheng S, Chen W, Deng H, et al. Glutamate dehydrogenase 1-dependent \u03b1-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome[J]. Clin Mol Hepatol. 2025;31(3):841\u201365.","journal-title":"Clin Mol Hepatol"},{"issue":"5","key":"3246_CR13","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.virs.2025.09.008","volume":"40","author":"Y Yan","year":"2025","unstructured":"Yan Y, Wei Z, Zheng M, et al. HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis[J]. Virol Sin. 2025;40(5):685\u201393.","journal-title":"Virol Sin"},{"key":"3246_CR14","doi-asserted-by":"crossref","unstructured":"Zhao Z, Wei Z, Zheng J, et al. Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways[J]. Volume 12. Emerging microbes & infections; 2023. p. 2261556. 2.","DOI":"10.1080\/22221751.2023.2261556"},{"issue":"1","key":"3246_CR15","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, Otsuka M, Funato K, et al. HBx-induced degradation of Smc5\/6 complex impairs homologous recombination-mediated repair of damaged DNA[J]. J Hepatol. 2022;76(1):53\u201362.","journal-title":"J Hepatol"},{"key":"3246_CR16","doi-asserted-by":"crossref","unstructured":"Vairetti M, Di Pasqua LG, Cagna M et al. Changes in Glutathione Content in Liver Diseases: An Update[J]. Antioxidants (Basel, Switzerland), 2021,10(3):364.","DOI":"10.3390\/antiox10030364"},{"issue":"2","key":"3246_CR17","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.ccell.2014.12.006","volume":"27","author":"L Jin","year":"2015","unstructured":"Jin L, Li D, Alesi GN, et al. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth[J]. Cancer Cell. 2015;27(2):257\u201370.","journal-title":"Cancer Cell"},{"issue":"12","key":"3246_CR18","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1111\/jgh.70090","volume":"40","author":"Q Ning","year":"2025","unstructured":"Ning Q, Yang P, Guan Y, et al. Deoxycholic Acid Promotes Persistent Low-Level Viremia in Chronic Hepatitis B via Enhancing HBV Particle Formation[J]. J Gastroenterol Hepatol. 2025;40(12):2997\u20133008.","journal-title":"J Gastroenterol Hepatol"},{"issue":"5","key":"3246_CR19","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s13139-024-00849-2","volume":"58","author":"MH Cheng","year":"2024","unstructured":"Cheng MH, Xie LJ. Synthesis and Biologic Evaluation of an Iodine-Labeled Entecavir Derivative for Anti-hepatitis B Virus Activity[J]. Nuclear Med Mol imaging. 2024;58(5):279\u201390.","journal-title":"Nuclear Med Mol imaging"},{"issue":"6773","key":"3246_CR20","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/35003506","volume":"404","author":"H Tanaka","year":"2000","unstructured":"Tanaka H, Arakawa H, Yamaguchi T, et al. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage[J]. Nature. 2000;404(6773):42\u20139.","journal-title":"Nature"},{"issue":"3","key":"3246_CR21","first-page":"4713","volume":"17","author":"K Xiang","year":"2018","unstructured":"Xiang K, Wang B. Role of the PI3K\u2013AKT\u2013mTOR pathway in hepatitis B virus infection and replication[J]. Mol Med Rep. 2018;17(3):4713\u20139.","journal-title":"Mol Med Rep"},{"issue":"6","key":"3246_CR22","doi-asserted-by":"publisher","first-page":"156","DOI":"10.3390\/v9060156","volume":"9","author":"L Allweiss","year":"2017","unstructured":"Allweiss L, Dandri M. The Role of cccDNA in HBV Maintenance[J]. Viruses. 2017;9(6):156.","journal-title":"Viruses"},{"key":"3246_CR23","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.2147\/IDR.S252994","volume":"13","author":"X Ji","year":"2020","unstructured":"Ji X, Xia M, Zhou B, et al. Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog[J]. Infect drug Resist. 2020;13:1881\u20138.","journal-title":"Infect drug Resist"},{"issue":"11","key":"3246_CR24","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1093\/hmg\/ddaf047","volume":"34","author":"B Munro","year":"2025","unstructured":"Munro B, Hines D, Mueller JS, et al. Deoxynucleoside supplementation ameliorates the disease associated phenotypes in a zebrafish model of RRM2B mtDNA depletion syndrome[J]. Hum Mol Genet. 2025;34(11):967\u201377.","journal-title":"Hum Mol Genet"},{"key":"3246_CR25","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/srep00822","volume":"2","author":"M Kuo","year":"2012","unstructured":"Kuo M, Sy AJ, Xue L, et al. RRM2B suppresses activation of the oxidative stress pathway and is up-regulated by p53 during senescence[J]. Sci Rep. 2012;2:822.","journal-title":"Sci Rep"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-026-03246-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-026-03246-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-026-03246-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:23:43Z","timestamp":1791246223000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12985-026-03246-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3246"],"URL":"https:\/\/doi.org\/10.1186\/s12985-026-03246-7","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]},"assertion":[{"value":"22 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Ethics Committee of Children\u2019s Hospital of Chongqing Medical University (No. 2025154) and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all pediatric participants. Analyses of publicly available GEO datasets did not require additional ethical approval.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"238"}}