{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:05:13Z","timestamp":1781831113032,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006734","name":"Princeton University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006734","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), remains a major medical problem. HBV has a high propensity for progressing to chronicity and can result in severe liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma. CHB patients frequently present with viral coinfection, including human immunodeficiency virus type (HIV) and hepatitis delta virus. About 10% of chronic HIV carriers are also persistently infected with HBV, which can result in more exacerbated liver disease. Mechanistic studies of HBV\u2010induced immune responses and pathogenesis, which could be significantly influenced by HIV infection, have been hampered by the scarcity of immunocompetent animal models. Here, we demonstrate that humanized mice dually engrafted with components of a human immune system and a human liver supported HBV infection, which was partially controlled by human immune cells, as evidenced by lower levels of serum viremia and HBV replication intermediates in the liver. HBV infection resulted in priming and expansion of human HLA\u2010restricted CD8+ T cells, which acquired an activated phenotype. Notably, our dually humanized mice support persistent coinfections with HBV and HIV, which opens opportunities for analyzing immune dysregulation during HBV and HIV coinfection, and preclinical testing of novel immunotherapeutics.<\/jats:p>","DOI":"10.1002\/jmv.28930","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T05:12:50Z","timestamp":1688533970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Persistent hepatitis B virus and HIV coinfections in dually humanized mice engrafted with human liver and immune system"],"prefix":"10.1002","volume":"95","author":[{"given":"Glenn","family":"Hogan","sequence":"first","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology Princeton University  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Y.","family":"Winer","sequence":"additional","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology Princeton University  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Ahodantin","sequence":"additional","affiliation":[{"name":"Division of Virology, Pathogenesis and Cancer, Institute of Human Virology, Departments of Pharmacology, Microbiology and Immunology University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Sellau","sequence":"additional","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology Princeton University  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Huang","sequence":"additional","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology Princeton University  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Douam","sequence":"additional","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology Princeton University  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Funaki","sequence":"additional","affiliation":[{"name":"Division of Virology, Pathogenesis and Cancer, Institute of Human Virology, Departments of Pharmacology, Microbiology and Immunology University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Chiriboga","sequence":"additional","affiliation":[{"name":"Department of Pathology New York University Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishan","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Virology, Pathogenesis and Cancer, Institute of Human Virology, Departments of Pharmacology, Microbiology and Immunology University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9322-7252","authenticated-orcid":false,"given":"Alexander","family":"Ploss","sequence":"additional","affiliation":[{"name":"Lewis Thomas Laboratory, Department of Molecular Biology Princeton University  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30190-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31694-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14364"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0085-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13217"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11901-020-00541-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-11-310"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200108150-00002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.53.2503"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.11.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/520752"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01023"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa340"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20657"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40094"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077298"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.10.040"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.09.008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.08.034"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.04.022"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004032"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3791\/58645"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00817"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000475107"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081720"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007251"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07478-2"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2016.12.017"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2014.08.006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23314"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.005"},{"issue":"8","key":"e_1_2_9_33_1","first-page":"511","article-title":"Immune tolerant hepatitis B: a clinical dilemma","volume":"7","author":"Tran TT","year":"2011","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1615"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.152738"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94366"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30815"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000142"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/605675"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103020200"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.42"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.1.68-76.2003"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02844-06"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24249"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00219"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93024"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-052016-100332"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxs045"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201518"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2573"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091474"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91709"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.28930","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:26:25Z","timestamp":1696397185000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.28930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/jmv.28930"],"URL":"https:\/\/doi.org\/10.1002\/jmv.28930","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.13.540563","asserted-by":"object"}]},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"2023-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e28930"}}