{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:47:43Z","timestamp":1788515263259,"version":"build-2803163510"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R21HD087496, R01HD109252, R01HD098866"],"award-info":[{"award-number":["R21HD087496, R01HD109252, R01HD098866"]}]},{"DOI":"10.13039\/100021836","name":"Minnesota Masonic Charities","doi-asserted-by":"crossref","award":["Masonic Cross-Departmental Grant in Children's Health Research"],"award-info":[{"award-number":["Masonic Cross-Departmental Grant in Children's Health Research"]}],"id":[{"id":"10.13039\/100021836","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs), syncytiotrophoblasts (STBs), and organoids, and this study assessed the utility of TSCs as a model of HCMV infection in the first-trimester placenta. HCMV was found to non-productively infect TSCs, EVTs, and STBs. Immunofluorescence assays and flow cytometry experiments further revealed that infected TSCs frequently only express immediate early viral gene products. Similarly, RNA sequencing found that viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts. Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation, and Wingless\/Integrated signaling. Thus, while HCMV does not replicate in TSCs, infection may perturb trophoblast differentiation in ways that could interfere with placental function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Placental infection plays a central role in human cytomegalovirus (HCMV) pathogenesis during pregnancy, but the species specificity of HCMV and the limited availability and lifespan of primary trophoblasts have been persistent barriers to understanding how infection impacts this vital organ. Human trophoblast stem cells (TSCs) represent a new approach to modeling viral infection early in placental development. This study reveals that TSCs, like other stem cell types, restrict HCMV replication. However, infection perturbs the expression of genes involved in differentiation and cell fate determination, pointing to a mechanism by which HCMV could cause placental injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01935-23","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T09:00:45Z","timestamp":1709802045000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Human trophoblast stem cells restrict human cytomegalovirus replication"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7194-1540","authenticated-orcid":false,"given":"Tyler B.","family":"Rollman","sequence":"first","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9318-7470","authenticated-orcid":false,"given":"Zachary W.","family":"Berkebile","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-5063","authenticated-orcid":false,"given":"Hiroaki","family":"Okae","sequence":"additional","affiliation":[{"name":"Department of Informative Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian J.","family":"Bardwell","sequence":"additional","affiliation":[{"name":"Developmental Biology Center, Department of Genetics, Cell Biology and Development and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-1930","authenticated-orcid":false,"given":"Micah D.","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women\u2019s Health, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-7409","authenticated-orcid":false,"given":"Craig J.","family":"Bierle","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2034"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.20736"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4004(89)90002-7"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(92)90290-j"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu019"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.07.016"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.15.6808-6820.2000"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199203053261003"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2000.107110"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2005.09.015"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy1128"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00610-y"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1304718110"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.008"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707513114"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.07.060"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01606887"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6031346"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew077"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03674-14"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aao1680"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00087.2021"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis186"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14102145"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2012.683899"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.06.023"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01905-16"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.79794"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.156273"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.008"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.11.004"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.04.004"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916019116"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199749"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02442-10"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83286-0"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2020.06.005"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00803-14"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijns10010001"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.536150"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06337.x"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110653"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10120704"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.025"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-018-0409-2"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39823"},{"key":"e_1_3_4_50_2","first-page":"14549","article-title":"PRAME induces apoptosis and inhibits proliferation of leukemic cells in vitro and in vivo","volume":"8","author":"Xu Y","year":"2015","unstructured":"Xu Y, Yue Q, Wei H, Pan G. 2015. PRAME induces apoptosis and inhibits proliferation of leukemic cells in vitro and in vivo. Int J Clin Exp Pathol 8:14549\u201314555.","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007811"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.803244"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-021-00725-y"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0190"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199840"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.78.6.2831-2840.2004"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1077"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.7598-7602.1998"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.686"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78829"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1203\/pdr.0b013e318045be6d"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.6.4970-4979.1998"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.163428"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.01.006"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-015-0411-4"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049700"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00298-13"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41158-0"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0753-3"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.05.006"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002959"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515076112"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.071415"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc14e03s18"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2017.06.002"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.08.005"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_82_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.01935-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01935-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T19:16:33Z","timestamp":1715800593000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.01935-23"}},"subtitle":[],"editor":[{"given":"Anna Ruth","family":"Cliffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":80,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,16]]}},"alternative-id":["10.1128\/jvi.01935-23"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01935-23","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.12.13.571456","asserted-by":"object"}]},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]},"assertion":[{"value":"2023-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01935-23"}}