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Review
. 2022 Jun;106(12):4413-4426.
doi: 10.1007/s00253-022-12029-3. Epub 2022 Jun 28.

The roles of DNA methylation on the promotor of the Epstein-Barr virus (EBV) gene and the genome in patients with EBV-associated diseases

Linlin Zhang  1   2 , Ran Wang  3   4 , Zhengde Xie  5   6
Affiliations
Review

The roles of DNA methylation on the promotor of the Epstein-Barr virus (EBV) gene and the genome in patients with EBV-associated diseases

Linlin Zhang et al. Appl Microbiol Biotechnol. 2022 Jun.

Erratum in

Abstract

Epstein-Barr virus (EBV) is an oncogenic virus that is closely associated with several malignant and lymphoproliferative diseases. Studies have shown that the typical characteristic of EBV-associated diseases is aberrant methylation of viral DNA and the host genome. EBV gene methylation helps EBV escape from immune monitoring and persist in host cells. EBV controls viral gene promoter methylation by hijacking host epigenetic machinery to regulate the expression of viral genes. EBV proteins also interact with host epigenetic regulatory factors to mediate the methylation of the host's important tumour suppressor gene promoters, thereby participating in the occurrence of tumorigenesis. Since epigenetic modifications, including DNA methylation, are reversible in nature, drugs that target DNA methylation can be developed for epigenetic therapy against EBV-associated tumours. Various methylation modes in the host and EBV genomes may also be of diagnostic and prognostic value. This review summarizes the regulatory roles of DNA methylation on the promotor of EBV gene and host genome in EBV-associated diseases, proposes the application prospect of DNA methylation in early clinical diagnosis and treatment, and provides insight into methylation-based strategies against EBV-associated diseases. KEY POINTS: • Methylation of both the host and EBV genomes plays an important role in EBV-associated diseases. • The functions of methylation of the host and EBV genomes in the occurrence and development of EBV-associated diseases are diverse. • Methylation may be a therapeutic target or biomarker in EBV-associated diseases.

Keywords: DNA methylation; EBV-associated diseases; Epigenetics; Epstein–Barr virus.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Epigenetic markers of EBV gene promoters. The EBV circular episome genome is shown with viral promoters (left). Promoter usage and expression during latent and lytic infection depend on DNA methylation (right). Symbols: arrow, directions of the encoding; solid squares, active promoters; dotted squares, silent promoters
Fig. 2
Fig. 2
Schematic presentation of EBV regulation of host genome methylation in EBV-associated neoplasms
See this image and copyright information in PMC

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