{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:48:32Z","timestamp":1791215312912,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T00:00:00Z","timestamp":1459123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>During Epstein\u2013Barr virus (EBV) latency, the EBV genome is largely silenced by methylation. This silencing is overturned during the switch to the lytic cycle. A key event is the production of the viral protein Zta which binds to three Zta\u2010response elements (ZRE) from the Rta promoter (Rp), two of which (ZRE2 and ZRE3) include three CpG motifs methylated in the latent genome. The bisulphite pyrosequencing reaction was used to quantify the methylation of ZRE2, ZRE3a, and ZRE3b in EBV\u2010positive cell lines and in ex vivo samples of EBV\u2010related diseases, in order to assess whether the level of methylation in these ZREs could provide additional information to viral DNA load and serology in the characterization of EBV\u2010associated diseases. In PBMC from two patients with infectious mononucleosis, over time Rp became increasingly methylated whereas EBV load decreased. In tonsil from patients with chronic tonsillitis, the methylation was less than in EBV\u2010associated tumors, regardless of the viral load. This was even more striking when only the ZRE3a and ZRE3b were considered since some samples presented unbalanced profiles on ZRE2. EBV reactivation in cell culture showed that the reduction in the overall level of methylation was closely related to the production of unmethylated virions. Thus, an assessment of the level of methylation may help to better characterize EBV replication in PBMC and in biopsies with high EBV load, during infectious mononucleosis and EBV\u2010associated cancers. <jats:bold><jats:italic>J. Med. 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Grenoble Alpes UMI 3265 UJF\u2010CNRS EMBL, UVHCI Grenoble France"},{"name":"Department of Virology Grenoble Alpes University Hospital Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Lupo","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes UMI 3265 UJF\u2010CNRS EMBL, UVHCI Grenoble France"},{"name":"Department of Virology Grenoble Alpes University Hospital Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Touyana","family":"Semenova","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes UMI 3265 UJF\u2010CNRS EMBL, UVHCI Grenoble France"},{"name":"Department of Virology Grenoble Alpes University Hospital Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Grossi","sequence":"additional","affiliation":[{"name":"Univ. 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