{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:20:14Z","timestamp":1792448414701,"version":"4.5.0"},"reference-count":96,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["DP1-DO-33547, DP1-DA-046108, R01-AI-137011, R01-OD-034046"],"award-info":[{"award-number":["DP1-DO-33547, DP1-DA-046108, R01-AI-137011, R01-OD-034046"]}]},{"name":"HHS | National Institutes of Health","award":["T32 A1007447-25, F32 GM125442, K99\/R00 Al151256, R00-AI151256"],"award-info":[{"award-number":["T32 A1007447-25, F32 GM125442, K99\/R00 Al151256, R00-AI151256"]}]},{"name":"HHS | National Institutes of Health","award":["R01-HL156475"],"award-info":[{"award-number":["R01-HL156475"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Macrophages are important target cells for diverse viruses and thus represent a valuable system for studying virus biology. Isolation of primary human macrophages is done by culture of dissociated tissues or from differentiated blood monocytes, but these methods are both time consuming and result in low numbers of recovered macrophages. Here, we explore whether macrophages derived from human induced pluripotent stem cells (iPSCs)\u2014which proliferate indefinitely and potentially provide unlimited starting material\u2014could serve as a faithful model system for studying virus biology. Human iPSC-derived monocytes were differentiated into macrophages and then infected with HIV-1, dengue virus, or influenza virus as model human viruses. We show that iPSC-derived macrophages support the replication of these viruses with kinetics and phenotypes similar to human blood monocyte-derived macrophages. These iPSC-derived macrophages were virtually indistinguishable from human blood monocyte-derived macrophages based on surface marker expression (flow cytometry), transcriptomics (RNA sequencing), and chromatin accessibility profiling. iPSC lines were additionally generated from non-human primate (chimpanzee) fibroblasts. When challenged with dengue virus, human and chimpanzee iPSC-derived macrophages show differential susceptibility to infection, thus providing a valuable resource for studying the species-tropism of viruses. We also show that blood- and iPSC-derived macrophages both restrict influenza virus at a late stage of the virus lifecycle. Collectively, our results substantiate iPSC-derived macrophages as an alternative to blood monocyte-derived macrophages for the study of virus biology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Macrophages have complex relationships with viruses: while macrophages aid in the removal of pathogenic viruses from the body, macrophages are also manipulated by some viruses to serve as vessels for viral replication, dissemination, and long-term persistence. Here, we show that iPSC-derived macrophages are an excellent model that can be exploited in virology.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01563-23","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T14:00:29Z","timestamp":1707314429000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Macrophages derived from human induced pluripotent stem cells (iPSCs) serve as a high-fidelity cellular model for investigating HIV-1, dengue, and influenza viruses"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-3158","authenticated-orcid":false,"given":"Qing","family":"Yang","sequence":"first","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Barbachano-Guerrero","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence M.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teisha J.","family":"Rowland","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-9985","authenticated-orcid":false,"given":"Robin D.","family":"Dowell","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Linda Crnic Institute for Down Syndrome Boulder Branch, BioFrontiers Institute, Boulder, Colorado, USA"},{"name":"Department of Computer Science, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Allen","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Linda Crnic Institute for Down Syndrome Boulder Branch, BioFrontiers Institute, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4101-2705","authenticated-orcid":false,"given":"Cody J.","family":"Warren","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"},{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA"},{"name":"Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA"},{"name":"Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-1085","authenticated-orcid":false,"given":"Sara L.","family":"Sawyer","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA"},{"name":"Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3070"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000922"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01435"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.119010"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092821"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034339"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00514"},{"key":"e_1_3_4_9_2","volume-title":"The innate immune system","author":"Monie TP","year":"2017","unstructured":"Monie TP. 2017. Section 1 - a snapshot of the innate immune system. In The innate immune system. Academic Press."},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V54.2.485.485"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0054-y"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.017"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.05.003"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpsc.108"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151526"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2018.12.005"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.07.014"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes11050511"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38591"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2017_35"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1009673"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.646447"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.2.1657-1661.1997"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230716"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.66.4.2232-2239.1992"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.11.6338"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-9071(200004)60:4<425::aid-jmv10>3.0.co;2-a"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01310705"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000086"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.19.9877-9887.2002"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.146.1.218"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2001.65.427"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-2478(96)02620-x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/314680"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1993.48.324"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-0934(00)00215-9"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.06.006"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.2650-2657.1999"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.12.8163"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06743-11"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4665-4674.2004"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.18.1.151-156.1977"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1978.27.590"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02602-07"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344359"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004053"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00291-10"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914994107"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.10.004"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601770"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01455-15"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02200-10"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890090304"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029879"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.08.002"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0301-472x(98)00038-1"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112338099"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2023.102291"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109955"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01084"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01462"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182031"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120231"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2012.12.004"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.10.553"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-436212"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4396"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2955"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11050697"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00654-7"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134808"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07570-7"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.01.005"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v32.i6.10"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6166"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061801"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7837-3_12"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU1018-378RR"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.03.042"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3854"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.11.016"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201708-1562OC"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03190-3"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.101851"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.04.005"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061349"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1111-1_6"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185056"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt214"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv416"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00361-07"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01563-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01563-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T18:19:05Z","timestamp":1726510745000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.01563-23"}},"subtitle":[],"editor":[{"given":"Frank","family":"Kirchhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":96,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,19]]}},"alternative-id":["10.1128\/jvi.01563-23"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01563-23","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,19]]},"assertion":[{"value":"2023-10-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01563-23"}}