Regulation of Epstein-Barr virus life cycle and cell proliferation by histone H3K27 methyltransferase EZH2 in Akata cells

Takaya Ichikawa, Yusuke Okuno, Yoshitaka Sato, Fumi Goshima, Hironori Yoshiyama, Teru Kanda, Hiroshi Kimura, Takayuki Murata

Research output: Contribution to journalArticle

Abstract

Epigenetic modifications play a pivotal role in the expression of the genes of Epstein-Barr virus (EBV). We found that de novo EBV infection of primary B cells caused moderate induction of enhancer of zeste homolog 2 (EZH2), the major histone H3 lysine 27 (K27) methyltransferase. To investigate the role of EZH2, we knocked out the EZH2 gene in EBV-negative Akata cells by the CRISPR/Cas9 system and infected the cells with EBV, followed by selection of EBV-positive cells. During the latent state, growth of EZH2-knockout (KO) cells was significantly slower after infection compared to wild-type controls, despite similar levels of viral gene expression between cell lines. After induction of the lytic cycle by anti-IgG, KO of EZH2 caused notable induction of expression of both latent and lytic viral genes, as well as increases in both viral DNA replication and progeny production. These results demonstrate that EZH2 is crucial for the intricate epigenetic regulation of not only lytic but also latent gene expression in Akata cells.

Original languageEnglish
Article numbere00478-18
JournalmSphere
Volume3
Issue number6
DOIs
Publication statusPublished - 01-11-2018

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Life Cycle Stages
Human Herpesvirus 4
Cell Proliferation
Viral Genes
Gene Expression
Epigenomics
Clustered Regularly Interspaced Short Palindromic Repeats
Epstein-Barr Virus Infections
Viral DNA
Methyltransferases
DNA Replication
Histones
Lysine
histone methyltransferase
Enhancer of Zeste Homolog 2 Protein
B-Lymphocytes
Cell Line
Growth
Infection
Genes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Ichikawa, Takaya ; Okuno, Yusuke ; Sato, Yoshitaka ; Goshima, Fumi ; Yoshiyama, Hironori ; Kanda, Teru ; Kimura, Hiroshi ; Murata, Takayuki. / Regulation of Epstein-Barr virus life cycle and cell proliferation by histone H3K27 methyltransferase EZH2 in Akata cells. In: mSphere. 2018 ; Vol. 3, No. 6.
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Regulation of Epstein-Barr virus life cycle and cell proliferation by histone H3K27 methyltransferase EZH2 in Akata cells. / Ichikawa, Takaya; Okuno, Yusuke; Sato, Yoshitaka; Goshima, Fumi; Yoshiyama, Hironori; Kanda, Teru; Kimura, Hiroshi; Murata, Takayuki.

In: mSphere, Vol. 3, No. 6, e00478-18, 01.11.2018.

Research output: Contribution to journalArticle

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