{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T04:24:22Z","timestamp":1793075062209,"version":"4.5.0"},"reference-count":114,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["302128021"],"award-info":[{"award-number":["302128021"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Research Priority Program UZH"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Macrophages conduct first-in-line defense against pathogens, including human adenovirus (AdV). AdVs cause respiratory disease, persist in immune cells, and, upon reactivation, are life-threatening to immunocompromised individuals. Here, our single-cell, single-virus experiments showed that AdV-type-C5 entry into human induced-pluripotent stem cell-derived macrophages is attenuated at cell binding and endosomal escape. A significant fraction (~30%) of the double-stranded viral DNA (vDNA) reaches the cell nucleus; however, it failed to efficiently express the immediate-early viral epigenetic regulator E1A. E1A transcription of silenced vDNA was rescued by E1A expression from a heterologous promoter of a superinfecting AdV, and allowed for full viral replication and progeny formation, even days post-infection, indicating long-lived infectivity of dormant vDNA. Bulk RNA-seq analyses showed that attenuated single AdV-C5 infections upregulated signaling, defense, and proinflammatory genes, whereas productive coinfections upregulated DNA replication and signaling pathways. Together, our data demonstrate that macrophages are a Trojan horse for AdV, notably independent of interferon, raising the possibility that macrophages function as a reservoir for AdV\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and reactivate dormant virus via epigenetic signals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      AdV are widespread, cause severe respiratory disease, persist in immune cells, and, upon reactivation, cause life-threatening conditions in immunocompromised individuals. Here, we show that human macrophages are either protected or susceptible to AdV, depending on the cell state, notably in an interferon-independent manner. The decisive cell state switch is the viral immediate-early transcription modulator E1A, which turns a repressive state into a permissive one and allows for the transactivation of dormant AdV-C5 genomes and viral progeny production. The data raise the possibility that macrophages are a hub for AdV persistence and epigenetic reactivation\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , in line with the notion that these cells resist immune clearance and serve as reservoirs for HIV, herpesvirus, SARS-CoV-2, or rubella virus infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00392-26","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:59:49Z","timestamp":1777906789000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional transactivation turns human iPSC-derived macrophages into an adenovirus-producing cell state"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-3008","authenticated-orcid":true,"given":"Maarit","family":"Suomalainen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Life Sciences, University of Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walther","family":"Haenseler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Life Sciences, University of Zurich","place":["Zurich, Switzerland"]},{"name":"Department of Biology, Institute of Molecular Systems Biology, ETH Zurich","place":["Zurich, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"URPP Adaptive Brain Circuits in Development and Learning, University of Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Kolibius","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4191-5306","authenticated-orcid":true,"given":"Andreas","family":"Pl\u00fcckthun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0400-1660","authenticated-orcid":true,"given":"Patrick","family":"Hearing","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-120X","authenticated-orcid":true,"given":"Urs F.","family":"Greber","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Life Sciences, University of Zurich","place":["Zurich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.08.006"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12050492"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13696"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000694"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01661-4"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01349-3"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.70063"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(84)90175-2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(01)00512-1"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.488"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-110615-042226"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37249-4"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1584923"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13576"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25441"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19497-0"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(78)90048-7"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209040"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.10.004"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00805-18"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13697"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11020141"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155546"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00104-08"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2023114162"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.252544"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005415"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00442-22"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15844-2"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00454-24"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00562-10"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01825-24"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1997.tb00587.x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.20.9655-9667.2000"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1391"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00670-17"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236008"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004696"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw499"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.12.013"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071098"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.05.017"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.05.018"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01833-13"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006914"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-092818-015550"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.07.006"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.09.004"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.4.1992-2000.2005"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.006"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006455"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.064"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-6-174"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.06.057"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-02-0121"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1201-1092"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02639-14"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.08.010"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2015794118"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl7150"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.68.3.1597-1604.1994"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.2217\/fon.11.81"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14071407"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.5.11.3214-3221.1985"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.20.120186.000401"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm827"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2023.121"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13694"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3324"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00848-y"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.7.4502-4508.1996"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15072-8"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44298-025-00110-3"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14909"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2014-0303"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.65.9.5084-5087.1991"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/20.24.6555"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2003.09.005"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180628"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.3.1224-1233.2000"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.12.005"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00225-9"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90534-V"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01265-10"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101365"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0438"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14050888"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.12.017"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.173"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09393-1"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60534-6"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.01.013"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09362-3"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04319-0"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2840"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302058"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83142-0"},{"key":"e_1_3_4_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90382-z"},{"key":"e_1_3_4_100_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1406"},{"key":"e_1_3_4_101_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00525.x"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2003.08.014"},{"key":"e_1_3_4_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.01.002"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1002"},{"key":"e_1_3_4_105_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06181-11"},{"key":"e_1_3_4_106_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-10-r100"},{"key":"e_1_3_4_107_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_4_108_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1104-8"},{"key":"e_1_3_4_109_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_3_4_110_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1087"},{"key":"e_1_3_4_111_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_112_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxt026"},{"key":"e_1_3_4_113_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_4_114_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_3_4_115_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00392-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00392-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:47:12Z","timestamp":1783514832000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00392-26"}},"subtitle":[],"editor":[{"given":"Karl","family":"M\u00fcnger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":114,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,23]]}},"alternative-id":["10.1128\/jvi.00392-26"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00392-26","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"assertion":[{"value":"2026-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00392-26"}}