{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:32:15Z","timestamp":1791415935815,"version":"4.3.3"},"reference-count":83,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI45862"],"award-info":[{"award-number":["AI45862"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD87689"],"award-info":[{"award-number":["HD87689"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32-HL066987"],"award-info":[{"award-number":["T32-HL066987"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001245","name":"Jeffrey Modell Foundation","doi-asserted-by":"publisher","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}],"id":[{"id":"10.13039\/100001245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,11,23]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Natural killer cells (NK) defend against viruses. Decidual NK (dNK), which comprise \u223c70% of decidual leukocytes during early pregnancy, are poorly cytotoxic but promote placentation. Zika virus (ZIKV) can cause fetal loss and birth defects. A strong dNK-mediated antiviral defense could provide a barrier to placental infections. Here, we show that ZIKV infection transforms immune-tolerated trophoblasts into dNK targets because ZIKV replicates in the endoplasmic reticulum (ER) and causes ER stress, which triggers NK killing. Unlike in the case of other viral infections, dNK release their granules and kill ZIKV-infected trophoblasts. In a trophoblast-like cell line, human primary extravillous trophoblasts, 3D villous explants, and\n                    <jats:italic>\n                      Ifnar1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    pregnant mice, dNK reduce placental and fetal viral loads and protect against fetal loss.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2115410118","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T16:40:14Z","timestamp":1637080814000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Decidual NK cells kill Zika virus\u2013infected trophoblasts"],"prefix":"10.1073","volume":"118","author":[{"given":"Sumit","family":"Sen Santara","sequence":"first","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c2ngela C.","family":"Crespo","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Mulik","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Ovies","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"Boulenouar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-8415","authenticated-orcid":false,"given":"Jack L.","family":"Strominger","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6200-4715","authenticated-orcid":false,"given":"Judy","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.07.002"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.01.004"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.004"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.03019.x"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2008.02.012"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507977112"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1897"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100003"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1452"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.10.016"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1260149"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0698-6"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.03.001"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.11.006"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0965539515000066"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.12.007"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05749-11"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002804"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617927114"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2016.08.001"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(90)90128-E"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507835102"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.607669"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.019"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.522047"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.008"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707513114"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10110649"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00214"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-00379-8"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200086"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gan018"},{"key":"e_1_3_5_33_2","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.4049\/jimmunol.154.8.3771","article-title":"Human placental HLA-G expression is restricted to differentiated cytotrophoblasts","volume":"154","author":"McMaster M. T.","year":"1995","unstructured":"M. T. McMaster , Human placental HLA-G expression is restricted to differentiated cytotrophoblasts. J. Immunol. 154, 3771\u20133778 (1995).","journal-title":"J. Immunol."},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2003.01161.x"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00785-17"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2017.11.008"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix552"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101174"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.12.013"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-10-10"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.014"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-020-0618-6"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34979-2"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101902"},{"key":"e_1_3_5_45_2","article-title":"The NK receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells","author":"Sen Santara S.","year":"2021","unstructured":"S. Sen Santara , The NK receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells. bioRxiv 2021.10.31.466654. https:\/\/doi.org\/10.1101\/2021.10.31.466654 (2 November 2021).","journal-title":"bioRxiv"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201642627"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10110598"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aao1680"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18952"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13288"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.7.1093"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01151-07"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4068"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071193"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.12.008"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2008.11.003"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142364"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0038-4"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2010.12.002"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb5390"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0446-y"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00094"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16754-z"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30203"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02146"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200649"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16072-3"},{"key":"e_1_3_5_68_2","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1242\/dev.143768","article-title":"Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage","volume":"143","author":"Shao Q.","year":"2016","unstructured":"Q. Shao , Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage. Development 143, 4127\u20134136 (2016).","journal-title":"Development"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122678"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphereDirect.00120-18"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009132"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.6.2937"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901289"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109107"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05458-0"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00900-17"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb2154"},{"key":"e_1_3_5_78_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01977"},{"key":"e_1_3_5_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.12.010"},{"key":"e_1_3_5_80_2","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12185"},{"key":"e_1_3_5_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2016.48"},{"key":"e_1_3_5_82_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7120"},{"key":"e_1_3_5_83_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003257"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2115410118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2115410118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T05:34:00Z","timestamp":1726119240000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2115410118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":83,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2021,11,23]]}},"alternative-id":["10.1073\/pnas.2115410118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2115410118","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.741199821.793590425","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]},"assertion":[{"value":"2021-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2115410118"}}