Regulation of Epstein-Barr Virus Life Cycle and Cell Proliferation by Histone H3K27 Methyltransferase EZH2 in Akata Cells

Author:

Ichikawa Takaya1,Okuno Yusuke23,Sato Yoshitaka1ORCID,Goshima Fumi1,Yoshiyama Hironori4,Kanda Teru5,Kimura Hiroshi1ORCID,Murata Takayuki16

Affiliation:

1. Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

4. Department of Microbiology, Shimane University Faculty of Medicine, Izumo, Japan

5. Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

6. Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Japan

Abstract

The life cycle of EBV is regulated by epigenetic modifications, such as CpG methylation and histone modifications. Here, we found that the expression of EZH2, which encodes a histone H3K27 methyltransferase, was induced by EBV infection; therefore, we generated EZH2-KO cells to investigate the role of EZH2 in EBV-infected Akata B cells. Disruption of EZH2 resulted in increased expression of EBV genes during the lytic phase and, therefore, efficient viral replication and progeny production. Our results shed light on the mechanisms underlying reactivation from an epigenetic point of view and further suggest a role for EZH2 as a form of innate immunity that restricts viral replication in infected cells.

Funder

Takeda Science Foundation

Japan Agency for Medical Research and Development

Ministry of Education, Culture, Sports, Science and Technology

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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