{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:34:50Z","timestamp":1787495690483,"version":"build-2736575974"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2019,3,23]],"date-time":"2019-03-23T00:00:00Z","timestamp":1553299200000},"content-version":"am","delay-in-days":290,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T00:00:00Z","timestamp":1528243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T00:00:00Z","timestamp":1528243200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n                    Chimeric urokinase type plasminogen activator (uPA)\/severely severe combined immunodeficiency (SCID) mice reconstituted with humanized livers are useful for studying hepatitis B virus (HBV) infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in\u2010depth mechanistic studies in this\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    HBV infection model is lacking. To characterize HBV kinetics post\u2010inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p.i. Total intrahepatic HBV DNA, HBV covalently closed circular DNA (cccDNA), and HBV RNA was measured in a subset of mice at 2, 4, 6, 10, and 13 weeks p.i. HBV half\u2010life (t\n                    <jats:sub>1\/2<\/jats:sub>\n                    ) was estimated using a linear mixed\u2010effects model. During the first 6 hours p.i., serum HBV declined in repopulated uPA\/SCID mice with a t\n                    <jats:sub>1\/2<\/jats:sub>\n                    = 62 minutes (95% confidence interval [CI] = 59\u201067). Thereafter, viral decline slowed followed by a 2\u2010day lower plateau. Subsequent viral amplification was multiphasic with an initial mean doubling time of t\n                    <jats:sub>2<\/jats:sub>\n                    = 8 \u00b1 3 hours followed by an interim plateau before prolonged amplification (t\n                    <jats:sub>2<\/jats:sub>\n                    = 2 \u00b1 0.5 days) to a final HBV steady state of 9.3 \u00b1 0.3 log copies (cps)\/mL. Serum HBV and intrahepatic HBV DNA were positively correlated (R\n                    <jats:sup>2<\/jats:sup>\n                    = 0.98).\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    HBV infection in uPA\/SCID chimeric mice is highly dynamic despite the absence of an adaptive immune response. Serum HBV t\n                    <jats:sub>1\/2<\/jats:sub>\n                    in humanized uPA\/SCID mice was estimated to be \u223c1 hour regardless of inoculum size. The HBV acute infection kinetics presented here is an important step in characterizing this experimental model system so that it can be effectively used to elucidate the dynamics of the HBV life cycle and thus possibly reveal effective antiviral drug targets. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018).\n                  <\/jats:p>","DOI":"10.1002\/hep.29891","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T22:33:08Z","timestamp":1521844388000},"page":"473-484","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":44,"title":["Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics"],"prefix":"10.1097","volume":"68","author":[{"given":"Yuji","family":"Ishida","sequence":"first","affiliation":[{"name":"PhoenixBio Co., Ltd.,Hiroshima,Japan"},{"name":"Liver Research Project Center,Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tje Lin","family":"Chung","sequence":"additional","affiliation":[{"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine,Loyola University Medical Center,Maywood,IL"},{"name":"Institute of Biostatistics and Mathematical Modeling, Department of Medicine,Goethe University,Frankfurt,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Imamura","sequence":"additional","affiliation":[{"name":"Liver Research Project Center,Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Hiraga","sequence":"additional","affiliation":[{"name":"Liver Research Project Center,Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suranjana","family":"Sen","sequence":"additional","affiliation":[{"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine,Loyola University Medical Center,Maywood,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yokomichi","sequence":"additional","affiliation":[{"name":"PhoenixBio Co., Ltd.,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chise","family":"Tateno","sequence":"additional","affiliation":[{"name":"PhoenixBio Co., Ltd.,Hiroshima,Japan"},{"name":"Liver Research Project Center,Hiroshima University,Hiroshima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Canini","sequence":"additional","affiliation":[{"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine,Loyola University Medical Center,Maywood,IL"},{"name":"Centre for Immunity, Infection and Evolution,University of Edinburgh,Edinburgh,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics,Los Alamos National Laboratory,Los Alamos,NM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan 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