Regulation of Epstein-Barr virus reactivation from latency.
The Epstein-Barr virus (EBV) is a human gamma-herpesvirus that is implicated in various types of proliferative diseases. Upon infection, it predominantly establishes latency in B cells and cannot ever be eradicated; it persists for the host's lifetime. Reactivation of the virus from latency depends on expression of the viral immediate-early gene, BamHI Z fragment leftward open reading frame 1 (BZLF1). The BZLF1 promoter normally exhibits only low basal activity but is activated in response to chemical or biological inducers, such as 12-O-tetradecanoylphorbol-13-acetate, calcium ionophore, histone deacetylase inhibitor, or anti-Ig. Transcription from the BZLF1 promoter is activated by myocyte enhancer factor 2, specificity protein 1, b-Zip type transcription factors and mediating epigenetic modifications of the promoter, such as histone acetylation and H3K4me3. In contrast, repression of the promoter is mediated by transcriptional suppressors, such as ZEB, ZIIR-BP, and jun dimerization protein 2, causing suppressive histone modifications like histone H3K27me3, H3K9me2/3 and H4K20me3. Interestingly, there is little CpG DNA methylation of the promoter, indicating that DNA methylation is not crucial for suppression of BZLF1. This review will focus on the molecular mechanisms by which the EBV lytic switch is controlled and discuss the physiological significance of this switching for its survival and oncogenesis.
Department of Virology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan; Division of Virology, Aichi Cancer Center Research Institute, 1-Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Takayuki
T
Murata
D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014775:Virus Activation
C063676:BZLF1 protein, Herpesvirus 4, Human; D015534:Trans-Activators
BZLF1 protein; Epstein-Barr virus; latency; reactivation