{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:29:33Z","timestamp":1791221373825,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1006404","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000}}],"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T00:00:00Z","timestamp":1497484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA22443"],"award-info":[{"award-number":["P01 CA22443"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE023939"],"award-info":[{"award-number":["R01 DE023939"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA14520"],"award-info":[{"award-number":["P30 CA14520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 CA009135"],"award-info":[{"award-number":["T32 CA009135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 GM104940"],"award-info":[{"award-number":["U54 GM104940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1006404","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T21:26:25Z","timestamp":1497561985000},"page":"e1006404","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":83,"title":["Hypoxia-inducible factor-1\u03b1 plays roles in Epstein-Barr virus\u2019s natural life cycle and tumorigenesis by inducing lytic infection through direct binding to the immediate-early BZLF1 gene promoter"],"prefix":"10.1371","volume":"13","author":[{"given":"Richard J.","family":"Kraus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2186-3062","authenticated-orcid":true,"given":"Xianming","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blue-leaf A.","family":"Cordes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7270","authenticated-orcid":true,"given":"Saraniya","family":"Sathiamoorthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-4894","authenticated-orcid":true,"given":"Tawin","family":"Iempridee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjay M.","family":"Nawandar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shidong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-0568","authenticated-orcid":true,"given":"James C.","family":"Romero-Masters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle G.","family":"McChesney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen R.","family":"Makielski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis L.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Johannsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon C.","family":"Kenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4754-7594","authenticated-orcid":true,"given":"Janet E.","family":"Mertz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,6,15]]},"reference":[{"key":"ref1","article-title":"Fields Virology","author":"RM Longnecker","year":"2013"},{"key":"ref2","first-page":"151","article-title":"EBV Persistence\u2014Introducing the Virus","volume":"390","author":"DA Thorley-Lawson","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1038\/emm.2014.84","article-title":"Epstein-Barr virus latent genes","volume":"47","author":"M-S Kang","year":"2015","journal-title":"Exp Mol Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev.pathol.1.110304.100209","article-title":"Spectrum of Epstein-Barr virus-associated diseases","volume":"1","author":"JL Kutok","year":"2006","journal-title":"Annu Rev Pathol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.semcancer.2014.04.004","article-title":"Co-infections, inflammation and oncogenesis: future directions for EBV research","volume":"26","author":"AB Rickinson","year":"2014","journal-title":"Semin Cancer Biol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.biochi.2011.12.001","article-title":"The periodontal pathogen Porphyromonas gingivalis induces the Epstein-Barr virus lytic switch transactivator ZEBRA by histone modification","volume":"94","author":"K Imai","year":"2012","journal-title":"Biochimie"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"8028","DOI":"10.1128\/JVI.00722-14","article-title":"Activation and repression of Epstein-Barr Virus and Kaposi\u2019s sarcoma-associated herpesvirus lytic cycles by short- and medium-chain fatty acids","volume":"88","author":"KL Gorres","year":"2014","journal-title":"J Virol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"5810","DOI":"10.1128\/JVI.74.13.5810-5818.2000","article-title":"Transforming growth factor beta 1 stimulates expression of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA by an indirect mechanism which requires the MAPK kinase pathway","volume":"74","author":"H Fahmi","year":"2000","journal-title":"J Virol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"7836","DOI":"10.1128\/JVI.01197-10","article-title":"Transforming growth factor beta-induced reactivation of Epstein-Barr virus involves multiple Smad-binding elements cooperatively activating expression of the latent-lytic switch BZLF1 gene","volume":"85","author":"T Iempridee","year":"2011","journal-title":"J Virol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"16544","DOI":"10.1073\/pnas.1400818111","article-title":"Efficient replication of Epstein-Barr virus in stratified epithelium in vitro","volume":"111","author":"RM Temple","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1128\/JVI.61.12.3672-3679.1987","article-title":"Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency","volume":"61","author":"J Countryman","year":"1987","journal-title":"J Virol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.1073\/pnas.93.17.9194","article-title":"Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism","volume":"93","author":"S Zalani","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1128\/JVI.01790-12","article-title":"Viral genome methylation differentially affects the ability of BZLF1 versus BRLF1 to activate Epstein-Barr virus lytic gene expression and viral replication","volume":"87","author":"CK Wille","year":"2013","journal-title":"J Virol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1128\/JVI.64.3.1227-1232.1990","article-title":"Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1","volume":"64","author":"E Flemington","year":"1990","journal-title":"J Virol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"7978","DOI":"10.1128\/JVI.72.10.7978-7984.1998","article-title":"The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes","volume":"72","author":"T Ragoczy","year":"1998","journal-title":"J Virol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.semcancer.2014.01.002","article-title":"Regulation of the latent-lytic switch in Epstein-Barr virus","volume":"26","author":"SC Kenney","year":"2014","journal-title":"Semin Cancer Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.gde.2009.10.009","article-title":"HIF-1: upstream and downstream of cancer metabolism","volume":"20","author":"GL Semenza","year":"2010","journal-title":"Curr Opin Genet Dev"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc3183","article-title":"HIF1\u03b1 and HIF2\u03b1: sibling rivalry in hypoxic tumour growth and progression","volume":"12","author":"B Keith","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1053\/j.semnuclmed.2014.11.002","article-title":"The clinical significance of hypoxia in human cancers","volume":"45","author":"N Dhani","year":"2015","journal-title":"Semin Nucl Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-inducible factors and the response to hypoxic stress","volume":"40","author":"AJ Majmundar","year":"2010","journal-title":"Mol Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1146\/annurev-physiol-021909-135922","article-title":"Mammalian Per-Arnt-Sim proteins in environmental adaptation","volume":"72","author":"BE McIntosh","year":"2010","journal-title":"Annu Rev Physiol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.virol.2013.06.018","article-title":"Oxygen tension level and human viral infections","volume":"444","author":"F Morinet","year":"2013","journal-title":"Virology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.virol.2014.02.027","article-title":"Hypoxia-inducible factor 1 and its role in viral carcinogenesis","volume":"456\u2013457","author":"S Cuninghame","year":"2014","journal-title":"Virology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jcv.2006.06.013","article-title":"Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle","volume":"37","author":"J-H Jiang","year":"2006","journal-title":"J Clin Virol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"10148","DOI":"10.1128\/JVI.01002-13","article-title":"Contribution of myocyte enhancer factor 2 family transcription factors to BZLF1 expression in Epstein-Barr virus reactivation from latency","volume":"87","author":"T Murata","year":"2013","journal-title":"J Virol"},{"key":"ref26","first-page":"969","article-title":"Switching viral latency to viral lysis: a novel therapeutic approach for Epstein-Barr virus-associated neoplasia","volume":"56","author":"MI Guti\u00e9rrez","year":"1996","journal-title":"Cancer Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1128\/JVI.78.4.1893-1902.2004","article-title":"Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas","volume":"78","author":"W Feng","year":"2004","journal-title":"J Virol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/ijc.10515","article-title":"The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro","volume":"100","author":"PMJ Clement","year":"2002","journal-title":"Int J Cancer J Int Cancer"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"150018","DOI":"10.1098\/rsob.150018","article-title":"Ubiquitylation, neddylation and the DNA damage response","volume":"5","author":"JS Brown","year":"2015","journal-title":"Open Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e1003341","DOI":"10.1371\/journal.ppat.1003341","article-title":"Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity: implications for possible immune adjuvant therapy","volume":"9","author":"MJ Strong","year":"2013","journal-title":"PLoS Pathog"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e1005158","DOI":"10.1371\/journal.ppat.1005158","article-title":"Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma","volume":"11","author":"F Abate","year":"2015","journal-title":"PLoS Pathog"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"6761","DOI":"10.1128\/JVI.77.12.6761-6768.2003","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia","volume":"77","author":"M Haque","year":"2003","journal-title":"J Virol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"7965","DOI":"10.1128\/JVI.00689-06","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus latent protein LANA interacts with HIF-1 alpha to upregulate RTA expression during hypoxia: Latency control under low oxygen conditions","volume":"80","author":"Q Cai","year":"2006","journal-title":"J Virol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"8230","DOI":"10.1128\/JVI.72.10.8230-8239.1998","article-title":"Identification of a negative cis element within the ZII domain of the Epstein-Barr virus lytic switch BZLF1 gene promoter","volume":"72","author":"P Liu","year":"1998","journal-title":"J Virol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1128\/JVI.02615-10","article-title":"The ZIIR element of the Epstein-Barr virus BZLF1 promoter plays a central role in establishment and maintenance of viral latency","volume":"85","author":"X Yu","year":"2011","journal-title":"J Virol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"8245","DOI":"10.1073\/pnas.95.14.8245","article-title":"Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells","volume":"95","author":"HJ Delecluse","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref37","first-page":"1467","article-title":"The hypoxia-inducible miR-429 regulates hypoxia-inducible factor-1\u03b1 expression in human endothelial cells through a negative feedback loop","volume":"29","author":"S Bartoszewska","year":"2015","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"7892","DOI":"10.1128\/JVI.00379-10","article-title":"Differential expression of the miR-200 family microRNAs in epithelial and B cells and regulation of Epstein-Barr virus reactivation by the miR-200 family member miR-429","volume":"84","author":"Z Lin","year":"2010","journal-title":"J Virol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"10329","DOI":"10.1128\/JVI.00923-10","article-title":"Cellular microRNAs 200b and 429 regulate the Epstein-Barr virus switch between latency and lytic replication","volume":"84","author":"AL Ellis-Connell","year":"2010","journal-title":"J Virol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1128\/JVI.02781-14","article-title":"Cellular differentiation regulator BLIMP1 induces Epstein-Barr virus lytic reactivation in epithelial and B cells by activating transcription from both the R and Z promoters","volume":"89","author":"JA Reusch","year":"2015","journal-title":"J Virol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"7363","DOI":"10.1128\/JVI.00154-07","article-title":"X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D","volume":"81","author":"PM Bhende","year":"2007","journal-title":"J Virol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"13566","DOI":"10.1128\/JVI.01055-07","article-title":"Plasma cell-specific transcription factor XBP-1s binds to and transactivates the Epstein-Barr virus BZLF1 promoter","volume":"81","author":"CC Sun","year":"2007","journal-title":"J Virol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1371\/journal.ppat.0030194","article-title":"ZEB1 regulates the latent-lytic switch in infection by Epstein-Barr virus","volume":"3","author":"X Yu","year":"2007","journal-title":"PLoS Pathog"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"6139","DOI":"10.1128\/JVI.02706-09","article-title":"Either ZEB1 or ZEB2\/SIP1 can play a central role in regulating the Epstein-Barr virus latent-lytic switch in a cell-type-specific manner","volume":"84","author":"AL Ellis","year":"2010","journal-title":"J Virol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e1005195","DOI":"10.1371\/journal.ppat.1005195","article-title":"Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells","volume":"11","author":"DM Nawandar","year":"2015","journal-title":"PLoS Pathog"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1172\/JCI76357","article-title":"LMP1-deficient Epstein-Barr virus mutant requires T cells for lymphomagenesis","volume":"125","author":"S-D Ma","year":"2015","journal-title":"J Clin Invest"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.7150\/ijbs.16564","article-title":"Epstein-Barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis","volume":"12","author":"H Li","year":"2016","journal-title":"Int J Biol Sci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1128\/JVI.05167-11","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus latency-associated nuclear antigen induction by hypoxia and hypoxia-inducible factors","volume":"86","author":"RP Veeranna","year":"2012","journal-title":"J Virol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1182\/blood.V92.7.2260","article-title":"Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha","volume":"92","author":"MS Wiesener","year":"1998","journal-title":"Blood"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.canlet.2007.01.012","article-title":"Genome-wide expression analysis using microarray identified complex signaling pathways modulated by hypoxia in nasopharyngeal carcinoma","volume":"253","author":"FL Sung","year":"2007","journal-title":"Cancer Lett"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"7037","DOI":"10.1128\/JVI.00553-06","article-title":"Genetic Organization and Hypoxic Activation of the Kaposi\u2019s Sarcoma-Associated Herpesvirus ORF34-37 Gene Cluster","volume":"80","author":"M Haque","year":"2006","journal-title":"J Virol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"e1003750","DOI":"10.1371\/journal.ppat.1003750","article-title":"A unique SUMO-2-interacting motif within LANA is essential for KSHV latency","volume":"9","author":"Q Cai","year":"2013","journal-title":"PLoS Pathog"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"e42072","DOI":"10.1371\/journal.pone.0042072","article-title":"Epstein-Barr virus immortalization of human B-cells leads to stabilization of hypoxia-induced factor 1 alpha, congruent with the Warburg effect","volume":"7","author":"S Darekar","year":"2012","journal-title":"PloS One"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.1128\/MCB.24.12.5223-5234.2004","article-title":"Epstein-Barr virus latent membrane protein 1 induces synthesis of hypoxia-inducible factor 1 alpha","volume":"24","author":"N Wakisaka","year":"2004","journal-title":"Mol Cell Biol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"9870","DOI":"10.1158\/0008-5472.CAN-06-1679","article-title":"EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells","volume":"66","author":"S Kondo","year":"2006","journal-title":"Cancer Res"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1099\/vir.0.2008\/003392-0","article-title":"Epstein\u2013Barr virus-encoded EBNA1 modulates the AP-1 transcription factor pathway in nasopharyngeal carcinoma cells and enhances angiogenesis in vitro","volume":"89","author":"JD O\u2019Neil","year":"2008","journal-title":"J Gen Virol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"e1002516","DOI":"10.1371\/journal.ppat.1002516","article-title":"The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1","volume":"8","author":"AR Robinson","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"8053","DOI":"10.1128\/JVI.00546-13","article-title":"The B-cell-specific transcription factor and master regulator Pax5 promotes Epstein-Barr virus latency by negatively regulating the viral immediate early protein BZLF1","volume":"87","author":"RM Raver","year":"2013","journal-title":"J Virol"},{"key":"ref59","first-page":"2595","article-title":"Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival","volume":"8","author":"EP Hui","year":"2002","journal-title":"Clin Cancer Res Off J Am Assoc Cancer Res"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/hed.21877","article-title":"Targeting tumor hypoxia in nasopharyngeal carcinoma","volume":"35","author":"B Hong","year":"2013","journal-title":"Head Neck"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"9429","DOI":"10.1128\/JVI.00511-14","article-title":"Modulation of Kaposi\u2019s sarcoma-associated herpesvirus interleukin-6 function by hypoxia-upregulated protein 1","volume":"88","author":"L Giffin","year":"2014","journal-title":"J Virol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"3","author":"B Muz","year":"2015","journal-title":"Hypoxia Auckl NZ"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2147\/TCRM.S47434","article-title":"Therapeutic implications of Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma","volume":"10","author":"SH Hutajulu","year":"2014","journal-title":"Ther Clin Risk Manag"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1128\/JVI.02487-09","article-title":"The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production","volume":"84","author":"Q Meng","year":"2010","journal-title":"J Virol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev.med.60.041807.123243","article-title":"Oral iron chelators","volume":"60","author":"MD Cappellini","year":"2009","journal-title":"Annu Rev Med"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.freeradbiomed.2013.01.017","article-title":"Targeting dysregulation of brain iron homeostasis in Parkinson\u2019s disease by iron chelators","volume":"62","author":"O Weinreb","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1128\/JVI.03003-12","article-title":"Different patterns of Epstein-Barr virus latency in endemic Burkitt lymphoma (BL) lead to distinct variants within the BL-associated gene expression signature","volume":"87","author":"GL Kelly","year":"2013","journal-title":"J Virol"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.virol.2003.12.005","article-title":"A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer","volume":"320","author":"ST Oh","year":"2004","journal-title":"Virology"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"10113","DOI":"10.1128\/JVI.00692-07","article-title":"ZEB1 and c-Jun levels contribute to the establishment of highly lytic Epstein-Barr virus infection in gastric AGS cells","volume":"81","author":"W Feng","year":"2007","journal-title":"J Virol"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"14723","DOI":"10.1073\/pnas.95.25.14723","article-title":"Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization","volume":"95","author":"CM Counter","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1128\/MCB.01514-06","article-title":"The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo","volume":"27","author":"Q Yan","year":"2007","journal-title":"Mol Cell Biol"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1021\/bi970891w","article-title":"Ah receptor nuclear translocator protein heterogeneity is altered after heterodimerization with the Ah receptor","volume":"36","author":"JC Tsai","year":"1997","journal-title":"Biochemistry (Mosc)"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1128\/JVI.77.1.199-207.2003","article-title":"ZEB negatively regulates the lytic-switch BZLF1 gene promoter of Epstein-Barr virus","volume":"77","author":"RJ Kraus","year":"2003","journal-title":"J Virol"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1158\/1541-7786.MCR-06-0227","article-title":"Estrogen-related receptor alpha1 transcriptional activities are regulated in part via the ErbB2\/HER2 signaling pathway","volume":"5","author":"EA Ariazi","year":"2007","journal-title":"Mol Cancer Res MCR"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"8340","DOI":"10.1128\/JVI.70.12.8340-8347.1996","article-title":"A replication function associated with the activation domain of the Epstein-Barr virus Zta transactivator","volume":"70","author":"RT Sarisky","year":"1996","journal-title":"J Virol"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1128\/JVI.00573-10","article-title":"Epstein-Barr virus LF2 protein regulates viral replication by altering Rta subcellular localization","volume":"84","author":"AMF Heilmann","year":"2010","journal-title":"J Virol"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.celrep.2013.09.012","article-title":"Spontaneous lytic replication and epitheliotropism define an Epstein-Barr virus strain found in carcinomas","volume":"5","author":"M-H Tsai","year":"2013","journal-title":"Cell Rep"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1128\/JVI.01512-10","article-title":"A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas","volume":"85","author":"S-D Ma","year":"2011","journal-title":"J Virol"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"7976","DOI":"10.1128\/JVI.00770-12","article-title":"An Epstein-Barr Virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model","volume":"86","author":"S-D Ma","year":"2012","journal-title":"J Virol"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2144\/000112096","article-title":"Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli","volume":"40","author":"BK Tischer","year":"2006","journal-title":"BioTechniques"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/0092-8674(86)90803-2","article-title":"The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation","volume":"47","author":"N Raab-Traub","year":"1986","journal-title":"Cell"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinforma Oxf Engl"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"A McKenna","year":"2010","journal-title":"Genome Res"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"MA DePristo","year":"2011","journal-title":"Nat Genet"},{"key":"ref86","first-page":"11.10.1","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"GA Van der Auwera","year":"2013","journal-title":"Curr Protoc Bioinforma Ed Board Andreas Baxevanis Al"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrg3117","article-title":"Repetitive DNA and next-generation sequencing: computational challenges and solutions","volume":"13","author":"TJ Treangen","year":"2012","journal-title":"Nat Rev Genet"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"10696","DOI":"10.1128\/JVI.01457-14","article-title":"Comprehensive high-throughput RNA sequencing analysis reveals contamination of multiple nasopharyngeal carcinoma cell lines with HeLa cell genomes","volume":"88","author":"MJ Strong","year":"2014","journal-title":"J Virol"},{"key":"ref89","first-page":"7595","article-title":"CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells","volume":"182","author":"G Caron","year":"2009","journal-title":"J Immunol Baltim Md 1950"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1182\/blood-2009-07-235960","article-title":"An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization","volume":"114","author":"M Jourdan","year":"2009","journal-title":"Blood"},{"key":"ref91","first-page":"3931","article-title":"Characterization of a transitional preplasmablast population in the process of human B cell to plasma cell differentiation","volume":"187","author":"M Jourdan","year":"2011","journal-title":"J Immunol Baltim Md 1950"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1038\/leu.2014.61","article-title":"IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors","volume":"28","author":"M Jourdan","year":"2014","journal-title":"Leukemia"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"e1004077","DOI":"10.1371\/journal.pcbi.1004077","article-title":"GenomicScape: an easy-to-use web tool for gene expression data analysis. Application to investigate the molecular events in the differentiation of B cells into plasma cells","volume":"11","author":"A Kassambara","year":"2015","journal-title":"PLoS Comput Biol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1006404","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1006404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T07:01:01Z","timestamp":1602313261000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1006404"}},"subtitle":[],"editor":[{"given":"Paul D.","family":"Ling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,6,15]]},"references-count":93,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1006404","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1006404","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,15]]}}}