{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:45:22Z","timestamp":1785545122731,"version":"3.56.0"},"reference-count":100,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI137337"],"award-info":[{"award-number":["AI137337"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["CA228700"],"award-info":[{"award-number":["CA228700"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009784","name":"Starr Foundation","doi-asserted-by":"publisher","award":["I11-0043"],"award-info":[{"award-number":["I11-0043"]}],"id":[{"id":"10.13039\/100009784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>Epstein-Barr virus (EBV) was discovered as the first human tumor virus in endemic Burkitt lymphoma, the most common childhood cancer in sub-Saharan Africa. In Burkitt lymphoma and in 200,000 EBV-associated cancers per year, epigenetic mechanisms maintain viral latency, during which lytic cycle factors are silenced. This property complicated EBV\u2019s discovery and facilitates tumor immunoevasion. DNA methylation and chromatin-based mechanisms contribute to lytic gene silencing. Here, we identified histone chaperones CAF1 and HIRA, which have key roles in host DNA replication-dependent and replication-independent pathways, respectively, as important for EBV latency. EBV strongly upregulates CAF1 in newly infected B-cells, where viral genomes acquire histone 3.1 and 3.3 variants prior to the first mitosis. Since histone chaperones ATRX and DAXX also function in maintenance of EBV latency, our results suggest that EBV coopts multiple histone pathways to reprogram viral genomes and highlight targets for lytic induction therapeutic strategies.<\/jats:p>","DOI":"10.1128\/mbio.01063-20","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T09:08:43Z","timestamp":1603703323000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Histone Loaders CAF1 and HIRA Restrict Epstein-Barr Virus B-Cell Lytic Reactivation"],"prefix":"10.1128","volume":"11","author":[{"given":"Yuchen","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Trudeau","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8867-3669","authenticated-orcid":false,"given":"Yohei","family":"Narita","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8612-5597","authenticated-orcid":false,"given":"Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8536-8941","authenticated-orcid":false,"given":"Mingxiang","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-3418","authenticated-orcid":false,"given":"Benjamin E.","family":"Gewurz","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"},{"name":"Harvard Graduate Program in Virology, Harvard University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Fields virology","author":"Longnecker R","year":"2013","unstructured":"Longnecker R, Kieff E, Cohen J. 2013. Epstein-Barr virus. In Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, Racaniello VR, Roizman B (ed), Fields virology, 6th ed (electronic). Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-013023"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-22822-8_8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0249-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.04.008"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-110615-042358"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-020-00792-2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2018.08.012"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00238-19"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02247-18"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01723-19"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.11.004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008030"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.01.002"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-22834-1_8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.11.009"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2015.05.009"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00572-19"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112326"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.09008.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601853"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026567"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01895-14"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002376"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.03.025"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3437"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2461"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.5.2548-2565.2006"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02989-13"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06537-11"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.062"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81326-4"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80661-3"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1199082"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13941"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00226-19"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901314116"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01069-12"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004656"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510612103"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.2.397"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02264-08"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.037"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422580112"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321704111"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317608110"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.08.026"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04059"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007667"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx771"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01276-08"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01220-16"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01920-10"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.68.9.6069-6073.1994"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05158-11"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03189-14"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a013029"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005718"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90028-1"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001114"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12707"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.81153-0"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020181"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512775112"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz858"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001048"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06768-11"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06334-11"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.22.12308-12319.2004"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00116-08"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00478-18"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0724-y"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003695"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40228"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi051333h"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.159"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.12.005"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03208-z"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.10.004"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03568-13"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.11.5612-5626.2002"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085703"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085712"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab1803"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407320101"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.20.10427-10436.2002"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01419-16"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.3390\/v5071758"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2010.01.012"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2009.12.001"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000496"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-024703"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02487-09"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004890"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.04.005"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232381299"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01063-20","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01063-20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T22:02:48Z","timestamp":1646690568000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.01063-20"}},"subtitle":[],"editor":[{"given":"Blossom","family":"Damania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":100,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,10,27]]}},"alternative-id":["10.1128\/mBio.01063-20"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01063-20","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.28.067371","asserted-by":"object"}]},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,27]]},"assertion":[{"value":"2020-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01063-20"}}