{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T18:26:53Z","timestamp":1786818413672,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573064"],"award-info":[{"award-number":["82573064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303137"],"award-info":[{"award-number":["82303137"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073030"],"award-info":[{"award-number":["82073030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Epstein\u2010Barr virus (EBV) is a key oncogenic driver of nasopharyngeal carcinoma (NPC) and is closely associated with cisplatin resistance, but its roles in metabolic reprogramming and chemoresistance remain unclear. This study aimed to investigate the role of EBV in polyamine metabolic reprogramming and its underlying mechanism in mediating cisplatin resistance in NPC. Metabolomic and Metabolic Flux Analysis confirmed that EBV significantly enhances polyamine anabolism in NPC cells, with ODC1, the rate\u2010limiting enzyme of polyamine biosynthesis, transcriptionally upregulated by EBV\u2010BZLF1 via direct binding to its promoter. Functional experiments revealed that the ODC1\u2010spermidine axis promotes EBV replication and cell proliferation via eIF5A hypusination by upregulating EBV\u2010EAD and host TRAF1, respectively, and induces B\u2010to\u2010Z DNA transition to attenuate cGAS\u2010STING\u2010mediated innate immune responses. Clinically, high ODC1 expression was an independent prognostic marker for poor survival in NPC patients. In vitro and in vivo, ODC1 knockdown or pharmacological inhibition with DFMO effectively restored cisplatin sensitivity in EBV\u2010positive NPC cells, likely by reducing Z\u2010DNA formation and potentiating cisplatin\u2010induced innate immune responses. Collectively, our findings identify a novel EBV\u2010ODC1\u2010polyamine regulatory axis that promotes viral replication and confers a survival advantage to cancer cells, highlighting ODC1 as a promising therapeutic target to improve cisplatin efficacy in EBV\u2010positive NPC.<\/jats:p>","DOI":"10.1002\/advs.77204","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T17:57:56Z","timestamp":1786816676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EBV\u2010Driven ODC1 Upregulation Enhances Polyamine Anabolism to Promote Viral Replication and Cisplatin Resistance in Nasopharyngeal Carcinoma"],"prefix":"10.1002","author":[{"given":"Yueshuo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology Xiangya Hospital Central South University Changsha China"},{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Hu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxing","family":"Yang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Cai","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"},{"name":"Molecular Imaging Research Center of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Cao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"},{"name":"Molecular Imaging Research Center of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4062-1065","authenticated-orcid":false,"given":"Li","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Pathology Xiangya Hospital Central South University Changsha China"},{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9118-7622","authenticated-orcid":false,"given":"Feng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathology Xiangya Hospital Central South University Changsha China"},{"name":"National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010021\u201003824\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201006889\u20105"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011934"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2981"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201021\u20101059"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.32"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.05.032"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.30941"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.02.009"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010018\u20100662\u20102"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114072"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2022.12.004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500031200"},{"issue":"1","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s12964-023-01373-0","article-title":"Polyamines: Their Significance for Maintaining Health and Contributing to Diseases","volume":"21","author":"Xuan M.","year":"2023","journal-title":"Cell Communication and Signaling"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.06.020"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031284"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010018\u20100050\u20103"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.01.032"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2013.07.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010503"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.012"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00071"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010006\u20100325\u20103"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402\u2010023\u201000870\u20101"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oor.2023.100123"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201001624\u20104"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u20100151\u20109"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002369\u20106"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010026\u201002934\u20109"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2024.101438"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010025\u201006549\u20105"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002163\u20105"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10040628"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010011\u20109265\u20108"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00491"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8ob00030a"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.01.001"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci199716"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010021\u201000153\u20108"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202200130"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci182768"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77204","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77204","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T17:57:57Z","timestamp":1786816677000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":41,"alternative-id":["10.1002\/advs.77204"],"URL":"https:\/\/doi.org\/10.1002\/advs.77204","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]},"assertion":[{"value":"2026-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77204"}}