{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:24:12Z","timestamp":1772166252464,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Major Scientific and Technological Special Project during the Thirteenth Five-year Plan Period","award":["2017ZX10201201003"],"award-info":[{"award-number":["2017ZX10201201003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571949"],"award-info":[{"award-number":["81571949"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3\u00a0years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3\u00a0years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12985-021-01707-9","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T07:02:49Z","timestamp":1638169369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The dynamic changes of HBV quasispecies diversity in infancy after immunoprophylaxis failure: a prospective cohort study"],"prefix":"10.1186","volume":"18","author":[{"given":"Yi","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yarong","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangjun","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongping","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liguo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaibin","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingxiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caihong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"issue":"14","key":"1707_CR1","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1056\/NEJMra0801644","volume":"359","author":"JL Dienstag","year":"2008","unstructured":"Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359(14):1486\u2013500.","journal-title":"N Engl J Med"},{"issue":"4","key":"1707_CR2","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.jhep.2003.12.002","volume":"40","author":"CH Chen","year":"2004","unstructured":"Chen CH, et al. Hepatitis B virus transmission and hepatocarcinogenesis: a 9 year retrospective cohort of 13676 relatives with hepatocellular carcinoma. J Hepatol. 2004;40(4):653\u20139.","journal-title":"J Hepatol"},{"issue":"17","key":"1707_CR3","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1056\/NEJM199910213411702","volume":"341","author":"JL Dienstag","year":"1999","unstructured":"Dienstag JL, et al. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med. 1999;341(17):1256\u201363.","journal-title":"N Engl J Med"},{"issue":"22","key":"1707_CR4","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1056\/NEJMoa012452","volume":"346","author":"MM Jonas","year":"2002","unstructured":"Jonas MM, et al. Clinical trial of lamivudine in children with chronic hepatitis B. N Engl J Med. 2002;346(22):1706\u201313.","journal-title":"N Engl J Med"},{"issue":"3","key":"1707_CR5","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.jpeds.2004.05.046","volume":"145","author":"GE Kobak","year":"2004","unstructured":"Kobak GE, et al. Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger. J Pediatr. 2004;145(3):340\u20135.","journal-title":"J Pediatr"},{"issue":"5","key":"1707_CR6","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1002\/hep.30050","volume":"68","author":"S Wirth","year":"2018","unstructured":"Wirth S, et al. Efficacy and safety of peginterferon Alfa-2a (40KD) in children with chronic hepatitis B: the PEG-B-ACTIVE study. Hepatology. 2018;68(5):1681\u201394.","journal-title":"Hepatology"},{"issue":"1","key":"1707_CR7","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/01.mpg.0000243439.47334.4e","volume":"44","author":"BH Choe","year":"2007","unstructured":"Choe BH, et al. Long-term therapeutic efficacy of lamivudine compared with interferon-alpha in children with chronic hepatitis B: the younger the better. J Pediatr Gastroenterol Nutr. 2007;44(1):92\u20138.","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"Suppl 1","key":"1707_CR8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/jvh.13165","volume":"26","author":"H Fan","year":"2019","unstructured":"Fan H, et al. Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B. J Viral Hepat. 2019;26(Suppl 1):77\u201384.","journal-title":"J Viral Hepat"},{"issue":"Suppl 1","key":"1707_CR9","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/jvh.13154","volume":"26","author":"Y Liu","year":"2019","unstructured":"Liu Y, et al. Long-term efficacy and safety of peginterferon in the treatment of children with HBeAg-positive chronic hepatitis B. J Viral Hepat. 2019;26(Suppl 1):69\u201376.","journal-title":"J Viral Hepat"},{"issue":"2","key":"1707_CR10","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.jpeds.2005.09.020","volume":"148","author":"L D'Antiga","year":"2006","unstructured":"D\u2019Antiga L, et al. Combined lamivudine\/interferon-alpha treatment in \u201cimmunotolerant\u201d children perinatally infected with hepatitis B: a pilot study. J Pediatr. 2006;148(2):228\u201333.","journal-title":"J Pediatr"},{"issue":"5","key":"1707_CR11","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/jvh.12007","volume":"20","author":"U Poddar","year":"2013","unstructured":"Poddar U, et al. Cure for immune-tolerant hepatitis B in children: is it an achievable target with sequential combo therapy with lamivudine and interferon? J Viral Hepat. 2013;20(5):311\u20136.","journal-title":"J Viral Hepat"},{"issue":"6","key":"1707_CR12","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.jhep.2018.01.037","volume":"68","author":"S Zhu","year":"2018","unstructured":"Zhu S, et al. Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: a pilot open-label randomized study. J Hepatol. 2018;68(6):1123\u20138.","journal-title":"J Hepatol"},{"issue":"8","key":"1707_CR13","first-page":"604","volume":"27","author":"SS Zhu","year":"2019","unstructured":"Zhu SS, et al. A randomized controlled study on factors influencing the curative effect of sequential combined interferon and lamivudine therapy in children with immune-tolerant phase chronic hepatitis B. Chin J Hepatol. 2019;27(8):604\u20139.","journal-title":"Chin J Hepatol"},{"key":"1707_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.07.022","author":"S Zhu","year":"2019","unstructured":"Zhu S, et al. Early initiation of antiviral therapy contributes to a rapid and significant loss of serum HBsAg in infantile-onset hepatitis B. J Hepatol. 2019. https:\/\/doi.org\/10.1016\/j.jhep.2019.07.022.","journal-title":"J Hepatol"},{"issue":"5","key":"1707_CR15","doi-asserted-by":"publisher","first-page":"3071","DOI":"10.1128\/JVI.79.5.3071-3083.2005","volume":"79","author":"TJ Chambers","year":"2005","unstructured":"Chambers TJ, et al. Quasispecies heterogeneity within the E1\/E2 region as a pretreatment variable during pegylated interferon therapy of chronic hepatitis C virus infection. J Virol. 2005;79(5):3071\u201383.","journal-title":"J Virol"},{"issue":"5","key":"1707_CR16","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jhep.2008.12.018","volume":"50","author":"L Chen","year":"2009","unstructured":"Chen L, et al. Early changes of hepatitis B virus quasispecies during lamivudine treatment and the correlation with antiviral efficacy. J Hepatol. 2009;50(5):895\u2013905.","journal-title":"J Hepatol"},{"issue":"9","key":"1707_CR17","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1136\/gut.2010.226225","volume":"60","author":"F Liu","year":"2011","unstructured":"Liu F, et al. Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy. Gut. 2011;60(9):1269\u201377.","journal-title":"Gut"},{"issue":"5","key":"1707_CR18","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1002\/hep.21374","volume":"44","author":"NJ Shire","year":"2006","unstructured":"Shire NJ, et al. HCV kinetics, quasispecies, and clearance in treated HCV-infected and HCV\/HIV-1-coinfected patients with hemophilia. Hepatology. 2006;44(5):1146\u201357.","journal-title":"Hepatology"},{"issue":"5","key":"1707_CR19","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1136\/gutjnl-2019-318278","volume":"69","author":"Y Xiao","year":"2020","unstructured":"Xiao Y, et al. Quasispecies characteristic in \u201ca\u201d determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: a prospective nested case-control study. Gut. 2020;69(5):933\u201341.","journal-title":"Gut"},{"issue":"48 Pt B","key":"1707_CR20","doi-asserted-by":"publisher","first-page":"6627","DOI":"10.1016\/j.vaccine.2017.10.032","volume":"35","author":"Y Lu","year":"2017","unstructured":"Lu Y, et al. The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: a large prospective cohort study in China. Vaccine. 2017;35(48 Pt B):6627\u201333.","journal-title":"Vaccine"},{"issue":"4","key":"1707_CR21","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1053\/j.gastro.2006.01.011","volume":"130","author":"BF Chen","year":"2006","unstructured":"Chen BF, et al. High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases. Gastroenterology. 2006;130(4):1153\u201368.","journal-title":"Gastroenterology"},{"issue":"3","key":"1707_CR22","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.cmi.2014.10.007","volume":"21","author":"F Li","year":"2015","unstructured":"Li F, et al. Whole genome characterization of hepatitis B virus quasispecies with massively parallel pyrosequencing. Clin Microbiol Infect. 2015;21(3):280\u20137.","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"1707_CR23","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jinf.2017.04.012","volume":"75","author":"G Yang","year":"2017","unstructured":"Yang G, et al. Quasispecies characteristics in mother-to-child transmission of hepatitis B virus by next-generation sequencing. J Infect. 2017;75(1):48\u201358.","journal-title":"J Infect"},{"issue":"16","key":"1707_CR24","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.3748\/wjg.v24.i16.1708","volume":"24","author":"YM Choi","year":"2018","unstructured":"Choi YM, Lee SY, Kim BJ. Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression. World J Gastroenterol. 2018;24(16):1708\u201324.","journal-title":"World J Gastroenterol"},{"issue":"2","key":"1707_CR25","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/jgh.12831","volume":"30","author":"Q Zhang","year":"2015","unstructured":"Zhang Q, et al. Incidence of natural resistance mutations in naive chronic hepatitis B patients: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2015;30(2):252\u201361.","journal-title":"J Gastroenterol Hepatol"},{"issue":"8962","key":"1707_CR26","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1016\/S0140-6736(95)92599-6","volume":"345","author":"WF Carman","year":"1995","unstructured":"Carman WF, et al. Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA. Lancet. 1995;345(8962):1406\u20137.","journal-title":"Lancet"},{"issue":"1","key":"1707_CR27","first-page":"30","volume":"22","author":"K Koizumi","year":"1995","unstructured":"Koizumi K, et al. Diversity of quasispecies in various disease stages of chronic hepatitis C virus infection and its significance in interferon treatment. Hepatology. 1995;22(1):30\u20135.","journal-title":"Hepatology"},{"issue":"5","key":"1707_CR28","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.jhep.2004.01.019","volume":"40","author":"I Abbate","year":"2004","unstructured":"Abbate I, et al. HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin. J Hepatol. 2004;40(5):831\u20136.","journal-title":"J Hepatol"},{"issue":"3","key":"1707_CR29","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1136\/gutjnl-2016-312162","volume":"67","author":"L Allweiss","year":"2018","unstructured":"Allweiss L, et al. Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo. Gut. 2018;67(3):542\u201352.","journal-title":"Gut"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-021-01707-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-021-01707-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-021-01707-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T07:11:39Z","timestamp":1638169899000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-021-01707-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,29]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1707"],"URL":"https:\/\/doi.org\/10.1186\/s12985-021-01707-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-952457\/v1","asserted-by":"object"}]},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,29]]},"assertion":[{"value":"5 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experimental protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. This study was approved by the Ethics Committee of Peking University Health Science Center. Written informed consent was obtained from each subject.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"236"}}