{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:31:25Z","timestamp":1787877085725,"version":"build-2784847793"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000121","name":"Division of Mathematical Sciences","doi-asserted-by":"publisher","award":["1813011"],"award-info":[{"award-number":["1813011"]}],"id":[{"id":"10.13039\/100000121","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000121","name":"Division of Mathematical Sciences","doi-asserted-by":"publisher","award":["2051820"],"award-info":[{"award-number":["2051820"]}],"id":[{"id":"10.13039\/100000121","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH NIGMS","award":["R01GM152743"],"award-info":[{"award-number":["R01GM152743"]}]},{"name":"National Institute of Health","award":["01AI144112"],"award-info":[{"award-number":["01AI144112"]}]},{"name":"National Institute Health","award":["01AI158666"],"award-info":[{"award-number":["01AI158666"]}]},{"name":"National Institute of Health","award":["R01AI146917"],"award-info":[{"award-number":["R01AI146917"]}]},{"name":"National Institute of Health","award":["01AI138797"],"award-info":[{"award-number":["01AI138797"]}]},{"name":"National Institute of Health","award":["R01AI153236"],"award-info":[{"award-number":["R01AI153236"]}]},{"name":"National Institute of Health","award":["R01AI146917"],"award-info":[{"award-number":["R01AI146917"]}]},{"name":"National Institute of Health","award":["R01AI168048"],"award-info":[{"award-number":["R01AI168048"]}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-15-048-01-MPC"],"award-info":[{"award-number":["RSG-15-048-01-MPC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bull Math Biol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP\/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP\/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to <jats:inline-formula><jats:alternatives><jats:tex-math>$$99\\%$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:mrow>\n                    <mml:mn>99<\/mml:mn>\n                    <mml:mo>%<\/mml:mo>\n                  <\/mml:mrow>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula> viral production 1\u20133 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss.<\/jats:p>","DOI":"10.1007\/s11538-024-01284-2","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T19:01:32Z","timestamp":1712689292000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mathematical Models of Early Hepatitis B Virus Dynamics in Humanized Mice"],"prefix":"10.1007","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5386-6946","authenticated-orcid":false,"given":"Stanca M.","family":"Ciupe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3357-1817","authenticated-orcid":false,"given":"Harel","family":"Dahari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9322-7252","authenticated-orcid":false,"given":"Alexander","family":"Ploss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"issue":"19","key":"1284_CR1","doi-asserted-by":"publisher","first-page":"9652","DOI":"10.1128\/JVI.00867-09","volume":"83","author":"Shinichi Asabe","year":"2009","unstructured":"Asabe Shinichi, Wieland Stefan F, Chattopadhyay Pratip K, Roederer Mario, Engle Ronald E, Purcell Robert H, Chisari Francis V (2009) The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol 83(19):9652\u20139662","journal-title":"J Virol"},{"issue":"6","key":"1284_CR2","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1099\/vir.0.81920-0","volume":"87","author":"Antonio Bertoletti","year":"2006","unstructured":"Bertoletti Antonio, Gehring Adam J (2006) The immune response during hepatitis B virus infection. J Gen Virol 87(6):1439\u20131449","journal-title":"J Gen Virol"},{"issue":"2","key":"1284_CR3","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.jhep.2016.04.022","volume":"65","author":"Eva Billerbeck","year":"2016","unstructured":"Billerbeck Eva, Mommersteeg Michiel C, Shlomai Amir, Xiao Jing W, Andrus Linda, Bhatta Ankit, Vercauteren Koen, Michailidis Eleftherios, Dorner Marcus, Krishnan Anuradha et al (2016) Humanized mice efficiently engrafted with fetal hepatoblasts and syngeneic immune cells develop human monocytes and NK cells. J Hepatol 65(2):334\u2013343","journal-title":"J Hepatol"},{"issue":"3","key":"1284_CR4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/jmv.10291","volume":"69","author":"Vladimir P Chulanov","year":"2003","unstructured":"Chulanov Vladimir P, Shipulin German A, Schaefer Stephan, Gerlich Wolfram H (2003) Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without coinfection by other hepatitis viruses. J Med Virol 69(3):313\u2013323","journal-title":"J Med Virol"},{"issue":"1","key":"1284_CR5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/imr.12686","volume":"285","author":"Stanca M Ciupe","year":"2018","unstructured":"Ciupe Stanca M (2018) Modeling the dynamics of hepatitis B infection, immunity, and drug therapy. Immunol Rev 285(1):38\u201354","journal-title":"Immunol Rev"},{"issue":"12","key":"1284_CR6","doi-asserted-by":"publisher","first-page":"5050","DOI":"10.1073\/pnas.0603626104","volume":"104","author":"Stanca M Ciupe","year":"2007","unstructured":"Ciupe Stanca M, Ribeiro Ruy M, Nelson Patrick W, Dusheiko Geoffrey, Perelson Alan S (2007) The role of cells refractory to productive infection in acute hepatitis B viral dynamics. Proc Natl Acad Sci 104(12):5050\u20135055","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"1284_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jtbi.2007.02.017","volume":"247","author":"Stanca M Ciupe","year":"2007","unstructured":"Ciupe Stanca M, Ribeiro Ruy M, Nelson Patrick W, Perelson Alan S (2007) Modeling the mechanisms of acute hepatitis B virus infection. J Theor Biol 247(1):23\u201335","journal-title":"J Theor Biol"},{"issue":"7","key":"1284_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003730","volume":"10","author":"Stanca M Ciupe","year":"2014","unstructured":"Ciupe Stanca M, Ribeiro Ruy M, Perelson Alan S (2014) Antibody responses during hepatitis B viral infection. PLoS Comput Biol 10(7):e1003730","journal-title":"PLoS Comput Biol"},{"issue":"1944","key":"1284_CR9","doi-asserted-by":"publisher","first-page":"20202715","DOI":"10.1098\/rspb.2020.2715","volume":"288","author":"Stanca M Ciupe","year":"2021","unstructured":"Ciupe Stanca M, Vaidya Naveen K, Forde Jonathan E (2021) Early events in hepatitis B infection: the role of inoculum dose. Proc R Soc B 288(1944):20202715","journal-title":"Proc R Soc B"},{"issue":"4","key":"1284_CR10","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1053\/j.gastro.2005.01.049","volume":"128","author":"Harel Dahari","year":"2005","unstructured":"Dahari Harel, Major Marian, Zhang Xinan, Mihalik Kathleen, Rice Charles M, Perelson Alan S, Feinstone Stephen M, Neumann Avidan U (2005) Mathematical modeling of primary hepatitis C infection: noncytolytic clearance and early blockage of virion production. Gastroenterology 128(4):1056\u20131066","journal-title":"Gastroenterology"},{"issue":"6","key":"1284_CR11","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1053\/j.gastro.2017.08.034","volume":"153","author":"Mathilde Duss\u00e9aux","year":"2017","unstructured":"Duss\u00e9aux Mathilde, Masse-Ranson Guillemette, Darche Sylvie, Ahodantin James, Li Yan, Fiquet Oriane, Beaumont Elodie, Moreau Pierrick, Rivi\u00e8re Lise, Neuveut Christine et al (2017) Viral load affects the immune response to HBV in mice with humanized immune system and liver. Gastroenterology 153(6):1647\u20131661","journal-title":"Gastroenterology"},{"issue":"10","key":"1284_CR12","doi-asserted-by":"publisher","first-page":"4873","DOI":"10.4049\/jimmunol.1501362","volume":"195","author":"Zhong Fang","year":"2015","unstructured":"Fang Zhong, Li Jin, Xiaoyu Yu, Zhang Dandan, Ren Guangxu, Shi Bisheng, Wang Cong, Kosinska Anna D, Wang Sen, Zhou Xiaohui et al (2015) Polarization of monocytic myeloid-derived suppressor cells by hepatitis B surface antigen is mediated via ERK\/IL-6\/STAT3 signaling feedback and restrains the activation of T cells in chronic hepatitis B virus infection. J Immunol 195(10):4873\u20134883","journal-title":"J Immunol"},{"issue":"10","key":"1284_CR13","first-page":"3442","volume":"145","author":"CARLO Ferrari","year":"1990","unstructured":"Ferrari CARLO, Penna A, Bertoletti A, Valli A, Delgi Antoni A, Giuberti TIZIANA, Cavalli ALBERTINA, ANNE Petit MARIE (1990) Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Invest Med 145(10):3442\u20133449","journal-title":"J Invest Med"},{"issue":"8","key":"1284_CR14","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3390\/app6080219","volume":"6","author":"Jonathan E Forde","year":"2016","unstructured":"Forde Jonathan E, Ciupe Stanca M, Cintron-Arias Ariel, Lenhart Suzanne (2016) Optimal control of drug therapy in a hepatitis B model. Appl Sci 6(8):219","journal-title":"Appl Sci"},{"issue":"4","key":"1284_CR15","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1128\/JVI.01934-08","volume":"83","author":"Dieter Glebe","year":"2009","unstructured":"Glebe Dieter, Lorenz Heike, Gerlich Wolfram H, Butler Scott D, Tochkov Ilia A, Tennant BudC, Cote Paul, Menne Stephan (2009) Correlation of virus and host response markers with circulating immune complexes during acute and chronic woodchuck hepatitis virus infection. J Virol 83(4):1579\u20131591","journal-title":"J Virol"},{"issue":"1","key":"1284_CR16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1074-7613(00)80295-2","volume":"4","author":"Luca G Guidotti","year":"1996","unstructured":"Guidotti Luca G, Ishikawa Tetsuya, Hobbs Monte V, Matzke Brent, Schreiber Robert, Chisari Francis V (1996) Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4(1):25\u201336","journal-title":"Immunity"},{"issue":"5415","key":"1284_CR17","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1126\/science.284.5415.825","volume":"284","author":"Luca G Guidotti","year":"1999","unstructured":"Guidotti Luca G, Rochford Rosemary, Chung Josan, Shapiro Max, Purcell Robert, Chisari Francis V (1999) Viral clearance without destruction of infected cells during acute HBV infection. Science 284(5415):825\u2013829","journal-title":"Science"},{"issue":"1","key":"1284_CR18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ajpath.2013.09.008","volume":"184","author":"Tanuja L Gutti","year":"2014","unstructured":"Gutti Tanuja L, Knibbe Jaclyn S, Makarov Edward, Zhang Jinjin, Yannam Govardhana R, Gorantla Santhi, Sun Yimin, Mercer David F, Suemizu Hiroshi, Wisecarver James L et al (2014) Human hepatocytes and hematolymphoid dual reconstitution in treosulfan-conditioned uPA-NOG mice. Am J Pathol 184(1):101\u2013109","journal-title":"Am J Pathol"},{"issue":"8","key":"1284_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1011309","volume":"19","author":"Atesmachew Hailegiorgis","year":"2023","unstructured":"Hailegiorgis Atesmachew, Ishida Yuji, Collier Nicholson, Imamura Michio, Shi Zhenzhen, Reinharz Vladimir, Tsuge Masataka, Barash Danny, Hiraga Nobuhiko, Yokomichi Hiroshi et al (2023) Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics. PLoS Comput Biol 19(8):e1011309","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"1284_CR20","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000205","volume":"7","author":"Leeor Hershkovich","year":"2023","unstructured":"Hershkovich Leeor, Shekhtman Louis, Bazinet Michel, P\u00e2ntea Victor, Placinta Gheorge, Cotler Scott J, Vaillant Andrew, Dahari Harel (2023) Rapid monophasic HBsAg decline during nucleic-acid polymer-based therapy predicts functional cure. Hepatol Commun 7(8):e0205","journal-title":"Hepatol Commun"},{"issue":"7","key":"1284_CR21","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28930","volume":"95","author":"Glenn Hogan","year":"2023","unstructured":"Hogan Glenn, Winer Benjamin Y, Ahodantin James, Sellau Julie, Huang Tiffany, Douam Florian, Funaki Masaya, Chiriboga Luis, Lishan Su, Ploss Alexander (2023) Persistent hepatitis B virus and HIV coinfections in dually humanized mice engrafted with human liver and immune system. J Med Virol 95(7):e28930","journal-title":"J Med Virol"},{"issue":"2","key":"1284_CR22","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/hep.29891","volume":"68","author":"Yuji Ishida","year":"2018","unstructured":"Ishida Yuji, Chung Tje Lin, Imamura Michio, Hiraga Nobuhiko, Sen Suranjana, Yokomichi Hiroshi, Tateno Chise, Canini Laetitia, Perelson Alan S, Uprichard Susan L et al (2018) Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics. Hepatology 68(2):473\u2013484","journal-title":"Hepatology"},{"issue":"1","key":"1284_CR23","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41598-020-80594-6","volume":"11","author":"Sarah Kadelka","year":"2021","unstructured":"Kadelka Sarah, Dahari Harel, Ciupe Stanca M (2021) Understanding the antiviral effects of rnai-based therapy in HBeAg-positive chronic hepatitis B infection. Sci Rep 11(1):200","journal-title":"Sci Rep"},{"issue":"1","key":"1284_CR24","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1038\/s41598-020-58870-2","volume":"10","author":"Jin Hyang Kim","year":"2020","unstructured":"Kim Jin Hyang, Ghosh Alip, Ayithan Natarajan, Romani Sara, Khanam Arshi, Park Jang-June, Rijnbrand Rene, Tang Lydia, Sofia Michael J, Kottilil Shyam et al (2020) Circulating serum hbsag level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients. Sci Rep 10(1):1835","journal-title":"Sci Rep"},{"issue":"5","key":"1284_CR25","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1128\/JVI.74.5.2255-2264.2000","volume":"74","author":"Heike McClary","year":"2000","unstructured":"McClary Heike, Koch Rick, Chisari Francis V, Guidotti Luca G (2000) Relative sensitivity of hepatitis B virus and other hepatotropic viruses to the antiviral effects of cytokines. J Virol 74(5):2255\u20132264","journal-title":"J Virol"},{"key":"1284_CR26","unstructured":"Monolix version 2019r2. Antony, France: Lixoft SAS, (2019)"},{"issue":"5","key":"1284_CR27","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/hep.21364","volume":"44","author":"John M Murray","year":"2006","unstructured":"Murray John M, Purcell Robert H, Wieland Stefan F (2006) The half-life of hepatitis B virions. Hepatology 44(5):1117\u20131121","journal-title":"Hepatology"},{"issue":"49","key":"1284_CR28","doi-asserted-by":"publisher","first-page":"17780","DOI":"10.1073\/pnas.0508913102","volume":"102","author":"John M Murray","year":"2005","unstructured":"Murray John M, Wieland Stefan F, Purcell Robert H, Chisari Francis V (2005) Dynamics of hepatitis B virus clearance in chimpanzees. Proc Natl Acad Sci 102(49):17780\u201317785","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"1284_CR29","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1002\/hep.23778","volume":"52","author":"Avidan U Neumann","year":"2010","unstructured":"Neumann Avidan U, Phillips Sandra, Levine Idit, Ijaz Samreen, Dahari Harel, Eren Rachel, Dagan Shlomo, Naoumov Nikolai V (2010) Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells. Hepatology 52(3):875\u2013885","journal-title":"Hepatology"},{"issue":"1","key":"1284_CR30","first-page":"164","volume":"72","author":"S Rath","year":"1988","unstructured":"Rath S, Devey Madeleine E (1988) IgG subclass composition of antibodies to hbsag in circulating immune complexes from patients with hepatitis B virus infections. Clin Exp Immunol 72(1):164","journal-title":"Clin Exp Immunol"},{"key":"1284_CR31","doi-asserted-by":"publisher","first-page":"S508","DOI":"10.1016\/S0168-8278(18)31264-9","volume":"68","author":"L Shekhtman","year":"2018","unstructured":"Shekhtman L, Borochov N, Cotler S, Hershkovich L, Uprichard S, Al-Mahtab M, Bazinet M, Vaillant A, Dahari H (2018) Modeling serum HBsAg, HBV DNA and transaminase kinetics during REP 2139 monotherapy in chronic HBeAg+ HBV infection. J Hepatol 68:S508","journal-title":"J Hepatol"},{"issue":"1","key":"1284_CR32","doi-asserted-by":"publisher","first-page":"7837","DOI":"10.1038\/s41598-020-64122-0","volume":"10","author":"Louis Shekhtman","year":"2020","unstructured":"Shekhtman Louis, Cotler Scott J, Hershkovich Leeor, Uprichard Susan L, Bazinet Michel, Pantea Victor, Cebotarescu Valentin, Cojuhari Lilia, Jimbei Pavlina, Krawczyk Adalbert et al (2020) Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg. Sci Rep 10(1):7837","journal-title":"Sci Rep"},{"issue":"20","key":"1284_CR33","doi-asserted-by":"publisher","first-page":"11652","DOI":"10.1073\/pnas.1635109100","volume":"100","author":"Jesse Summers","year":"2003","unstructured":"Summers Jesse, Jilbert Allison R, Yang Wengang, Aldrich Carol E, Saputelli Jeffry, Litwin Samuel, Toll Eugene, Mason William S (2003) Hepatocyte turnover during resolution of a transient hepadnaviral infection. Proc Natl Acad Sci 100(20):11652\u201311659","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"1284_CR34","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1128\/JVI.77.1.68-76.2003","volume":"77","author":"Robert Thimme","year":"2003","unstructured":"Thimme Robert, Wieland Stefan, Steiger Carola, Ghrayeb John, Reimann Keith A, Purcell Robert H, Chisari Francis V (2003) CD8+ T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol 77(1):68\u201376","journal-title":"J Virol"},{"issue":"7","key":"1284_CR35","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1084\/jem.193.7.847","volume":"193","author":"Simon A Whalley","year":"2001","unstructured":"Whalley Simon A, Murray John M, Brown Dave, Webster George JM, Emery Vincent C, Dusheiko Geoffrey M, Perelson Alan S (2001) Kinetics of acute hepatitis B virus infection in humans. J Exp Med 193(7):847\u2013854","journal-title":"J Exp Med"},{"issue":"7","key":"1284_CR36","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1073\/pnas.0308478100","volume":"101","author":"Stefan F Wieland","year":"2004","unstructured":"Wieland Stefan F, Spangenberg Hans Christian, Thimme Robert, Purcell Robert H, Chisari Francis V (2004) Expansion and contraction of the hepatitis B virus transcriptional template in infected chimpanzees. Proc Natl Acad Sci 101(7):2129\u20132134","journal-title":"Proc Natl Acad Sci"}],"container-title":["Bulletin of Mathematical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-024-01284-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11538-024-01284-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-024-01284-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T06:19:35Z","timestamp":1714371575000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11538-024-01284-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,9]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["1284"],"URL":"https:\/\/doi.org\/10.1007\/s11538-024-01284-2","relation":{},"ISSN":["0092-8240","1522-9602"],"issn-type":[{"value":"0092-8240","type":"print"},{"value":"1522-9602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,9]]},"assertion":[{"value":"25 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"53"}}