EBV Exploits RNA m6A Modification to Promote Cell Survival and Progeny Virus Production During Lytic Cycle

Yusuke Yanagi; Takahiro Watanabe; Yuya Hara; Yoshitaka Sato; Hiroshi Kimura; Takayuki Murata

doi:10.3389/fmicb.2022.870816

EBV Exploits RNA m⁶A Modification to Promote Cell Survival and Progeny Virus Production During Lytic Cycle

Front Microbiol. 2022 Jun 15:13:870816. doi: 10.3389/fmicb.2022.870816. eCollection 2022.

Authors

Yusuke Yanagi¹, Takahiro Watanabe¹, Yuya Hara¹, Yoshitaka Sato¹, Hiroshi Kimura¹, Takayuki Murata^{1

2}

Affiliations

¹ Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Japan.

Abstract

N6-methyladenosine (m⁶A) mediates various biological processes by affecting RNA stability, splicing, and translational efficiency. The roles of m⁶A modification in Epstein-Barr virus (EBV) infection in the lytic phase are unclear. Here, knockout of the m⁶A methyltransferase, N6-methyladenosine methyltransferase-like 3 (METTL3), or inhibition of methylation by DAA or UZH1a decreased the expression of viral lytic proteins and reduced progeny virion production. Interestingly, cell growth and viability were decreased by induction of the lytic cycle in METTL3-knockout or inhibitor-treated cells. Apoptosis was induced in those conditions possibly because of a decreased level of the anti-apoptotic viral protein, BHRF1. Therefore, m⁶A shows potential as a target of lytic induction therapy for EBV-associated cancers, including Burkitt lymphoma.

Keywords: 3-deazaadenosine; EBV; METTL3; lytic cycle; m6A modification.