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Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation.
J Med Virol 2016; 88(10):1814-20JM

Abstract

During Epstein-Barr 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-response 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-positive cell lines and in ex vivo samples of EBV-related 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-associated 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-associated 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-associated cancers. J. Med. Virol. 88:1814-1820, 2016. © 2016 Wiley Periodicals, Inc.

Authors+Show Affiliations

Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France. Department of Virology, Grenoble Alpes University Hospital, Grenoble, France.Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France. Department of Virology, Grenoble Alpes University Hospital, Grenoble, France.Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France. Department of Virology, Grenoble Alpes University Hospital, Grenoble, France.Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France. Department of Virology, Grenoble Alpes University Hospital, Grenoble, France.Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France.Department of Cancer Clinical Chemistry, Grenoble Alpes University Hospital, Grenoble, France.Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France. Department of Infectious Diseases, Grenoble Alpes University Hospital, Grenoble, France.Department of Cancer Clinical Chemistry, Grenoble Alpes University Hospital, Grenoble, France.Univ. Grenoble Alpes UMI 3265 UJF-CNRS EMBL, UVHCI, Grenoble, France. Department of Virology, Grenoble Alpes University Hospital, Grenoble, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26990870

Citation

Germi, Raphaële, et al. "Methylation of Epstein-Barr Virus Rta Promoter in EBV Primary Infection, Reactivation and Lymphoproliferation." Journal of Medical Virology, vol. 88, no. 10, 2016, pp. 1814-20.
Germi R, Guigue N, Lupo J, et al. Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation. J Med Virol. 2016;88(10):1814-20.
Germi, R., Guigue, N., Lupo, J., Semenova, T., Grossi, L., Vermeulen, O., ... Morand, P. (2016). Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation. Journal of Medical Virology, 88(10), pp. 1814-20. doi:10.1002/jmv.24524.
Germi R, et al. Methylation of Epstein-Barr Virus Rta Promoter in EBV Primary Infection, Reactivation and Lymphoproliferation. J Med Virol. 2016;88(10):1814-20. PubMed PMID: 26990870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation. AU - Germi,Raphaële, AU - Guigue,Nicolas, AU - Lupo,Julien, AU - Semenova,Touyana, AU - Grossi,Laurence, AU - Vermeulen,Odile, AU - Epaulard,Olivier, AU - de Fraipont,Florence, AU - Morand,Patrice, Y1 - 2016/03/28/ PY - 2016/03/15/accepted PY - 2016/3/19/entrez PY - 2016/3/19/pubmed PY - 2017/8/2/medline KW - EBV-associated cancers KW - Rta promoter KW - infectious mononucleosis KW - methylation KW - pyrosequencing SP - 1814 EP - 20 JF - Journal of medical virology JO - J. Med. Virol. VL - 88 IS - 10 N2 - During Epstein-Barr 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-response 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-positive cell lines and in ex vivo samples of EBV-related 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-associated 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-associated 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-associated cancers. J. Med. Virol. 88:1814-1820, 2016. © 2016 Wiley Periodicals, Inc. SN - 1096-9071 UR - https://www.unboundmedicine.com/medline/citation/26990870/Methylation_of_Epstein_Barr_virus_Rta_promoter_in_EBV_primary_infection_reactivation_and_lymphoproliferation_ L2 - https://doi.org/10.1002/jmv.24524 DB - PRIME DP - Unbound Medicine ER -