{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:07:07Z","timestamp":1789697227168,"version":"4.0.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100023885","name":"All of Us Research Program","doi-asserted-by":"crossref","award":["R01AI144112 and R01AI146917"],"award-info":[{"award-number":["R01AI144112 and R01AI146917"]}],"id":[{"id":"10.13039\/100023885","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17KK0194"],"award-info":[{"award-number":["17KK0194"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["fk0310513h0001, JP20fk0310109h0004"],"award-info":[{"award-number":["fk0310513h0001, JP20fk0310109h0004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Chronic hepatitis B virus (HBV) infection poses a significant global health threat, causing severe liver diseases including cirrhosis and hepatocellular carcinoma. We characterized HBV DNA kinetics in primary human hepatocytes (PHHs) over 32 days post-inoculation (p.i.) and modified our\n                      <jats:italic toggle=\"yes\">in-vivo<\/jats:italic>\n                      agent-based modeling (ABM) to gain insights into the HBV lifecycle and spread\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Parallel PHH cultures were mock-treated or treated with HBV entry inhibitor Myr-preS1 (6.25 \u00b5g\/mL) was initiated 24 h p.i. In untreated PHH, three viral DNA kinetic patterns were identified: (i) an initial decline, followed by (ii) rapid amplification and (iii) slower amplification\/accumulation. In the presence of Myr-preS1, viral DNA and infected cell numbers in phase 3 were effectively blocked, with minimal to no increase. This suggests that phase 2 represents viral amplification in initially infected cells, while phase 3 corresponds to viral spread to na\u00efve cells. The ABM reproduced well the HBV kinetic patterns observed and predicted that the viral eclipse phase lasts between 18 and 38 h. After the eclipse phase, the viral production rate increased over time, starting with a slow production cycle of 1 virion per day, which gradually accelerated to 1 virion per hour after 3 days. Approximately 4 days later, virion production reached a steady state production rate of 4 virions\/h. The estimated median efficacy of Myr-preS1 in blocking HBV spread was 91% (range: 90\u201392%). The HBV kinetics and the predicted estimates of the HBV eclipse phase duration and HBV production cycles in PHH are similar to those predicted in uPA\/SCID mice with human livers.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        While primary human hepatocytes (PHHs) are the most physiologically relevant culture system for studying HBV infection\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        , a comprehensive understanding of HBV infection kinetics and spread in PHH is lacking. In this study, we characterize HBV viral kinetics and modify our\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        agent-based modeling (ABM) to provide quantitative insights into the HBV production cycle and viral spread in PHH. The ABM provides an estimate of the HBV eclipse phase duration, HBV production cycles, and Myr-preS1 efficacy in blocking HBV spread in PHH. The results resemble those predicted in uPA\/SCID mice with human livers, demonstrating that estimated HBV infection kinetic parameters in PHH\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        mirror those observed in the\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        HBV infection chimeric mouse model.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00927-25","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T13:00:21Z","timestamp":1754312421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Modeling of hepatitis B virus infection spread in primary human hepatocytes"],"prefix":"10.1128","volume":"99","author":[{"given":"Zhenzhen","family":"Shi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0075gfd51","id-type":"ROR","asserted-by":"publisher"}],"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago","place":["Maywood, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7591-8287","authenticated-orcid":false,"given":"Masataka","family":"Tsuge","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0075gfd51","id-type":"ROR","asserted-by":"publisher"}],"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago","place":["Maywood, USA"]},{"id":[{"id":"https:\/\/ror.org\/038dg9e86","id-type":"ROR","asserted-by":"publisher"}],"name":"Liver Center, Hiroshima University Hospital","place":["Hiroshima, Japan"]},{"name":"Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholson","family":"Collier","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04b6x2g63","id-type":"ROR","asserted-by":"publisher"}],"name":"Consortium for Advanced Science and Engineering, University of Chicago","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/05gvnxz63","id-type":"ROR","asserted-by":"publisher"}],"name":"Decision and Infrastructure Sciences, Argonne National Laboratory","place":["Lemont, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasue","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine","place":["Ichikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Uchida","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01nyv7k26","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Travel Medicine and Health, Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University","place":["Yufu, Japan"]},{"name":"Department of Gastroenterology, Faculty of Medicine, Oita University","place":["Yufu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn M.","family":"Rutter","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Hutchinson Institute for Cancer Outcomes Research, Biostatistics Program, Public Health Sciences Division","place":["Seattle, 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