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

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

doi:10.3389/fmicb.2022.870816

Cited by 14 publications

(8 citation statements)

References 36 publications

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“…The proteins encoded by the m 6 A peaks of the PRV transcripts were involved in nearly every progression of the PRV life cycle, such as viral entry and intercellular diffusion (Pomeranz et al, 2005), DNA replication, repair and recombination (Ben-Porat et al, 1983), assembly of viral particles (Kopp et al, 2002), viral nuclear export (Wagenaar et al, 1995), capsid assembly and maturation (Pomeranz et al, 2005), among others. Similar to EBV (Xia et al, 2021;Yanagi et al, 2022) and KSHV (Baquero-Perez et al, 2019), which belonged to the Herpesviridae family, the majority of m 6 A peaks were distributed on the CDS of viral mRNAs, especially the 3′ end, suggesting that m 6 A modification might regulate viral gene transcription or translation and play a role in viral assembly and replication.…”

Section: Discussionmentioning

confidence: 97%

Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication

Cao

et al. 2023

Front. Microbiol.

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IntroductionPseudorabies virus (PRV) is the pathogenic virus of porcine pseudorabies (PR), belonging to the Herpesviridae family. PRV has a wide range of hosts and in recent years has also been reported to infect humans. N6-methyladenosine (m6A) modification is the major pathway of RNA post-transcriptional modification. Whether m6A modification participates in the regulation of PRV replication is unknown.MethodsHere, we investigated that the m6A modification was abundant in the PRV transcripts and PRV infection affected the epitranscriptome of host cells. Knockdown of cellular m6A methyltransferases METTL3 and METTL14 and the specific binding proteins YTHDF2 and YTHDF3 inhibited PRV replication, while silencing of demethylase ALKBH5 promoted PRV output. The overexpression of METTL14 induced more efficient virus proliferation in PRV-infected PK15 cells. Inhibition of m6A modification by 3-deazaadenosine (3-DAA), a m6A modification inhibitor, could significantly reduce viral replication.Results and DiscussionTaken together, m6A modification played a positive role in the regulation of PRV replication and gene expression. Our research revealed m6A modification sites in PRV transcripts and determined that m6A modification dynamically mediated the interaction between PRV and host.

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Section: Discussionmentioning

confidence: 97%

Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication

Cao

et al. 2023

Front. Microbiol.

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“…HEK293T and HEK293T/EBV cells were grown in DMEM (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% FBS. Akata(-) cells, Akata/EBV-EGFP [ 53 ], and LCLs established by recombinant EBV infection were maintained in RPMI 1640 supplemented with 10%-15% FBS. AGS/EBV-EGFP cells (kindly gifted by Hironori Yoshiyama) [ 54 ] were grown in RPMI 1640 medium containing 10% FBS and 750 μg/mL G418 [ 55 ].…”

Section: Methodsmentioning

confidence: 99%

Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation

Sagou,

Sato,

Okuno

et al. 2024

PLoS Pathog

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Epstein-Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus that is causally associated with several malignancies. In addition to latent factors, lytic replication contributes to cancer development. In this study, we examined whether the lytic gene BNRF1, which is conserved among gamma-herpesviruses, has an important role in lymphomagenesis. We found that lymphoblastoid cell lines (LCLs) established by BNRF1-knockout EBV exhibited remarkably lower pathogenicity in a mice xenograft model than LCLs produced by wild-type EBV (LCLs-WT). RNA-seq analyses revealed that BNRF1 elicited the expression of interferon-inducible protein 27 (IFI27), which promotes cell proliferation. IFI27 knockdown in LCLs-WT resulted in excessive production of reactive oxygen species, leading to cell death and significantly decreased their pathogenicity in vivo. We also confirmed that IFI27 was upregulated during primary infection in B-cells. Our findings revealed that BNRF1 promoted robust proliferation of the B-cells that were transformed by EBV latent infection via IFI27 upregulation both in vitro and in vivo.

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“…Treatment for tumors generally comprises surgery, hormonal therapy, Chemo/Target therapy, immunotherapy, radiotherapy, viruses/bacteria ( Yanagi et al, 2022 ), and more recently personalized therapy ( Beck et al, 2021 ; Inoue et al, 2021 ). The first-line treatment for low-grade hormone receptor-positive metastatic endometrial cancer includes platinum-based chemotherapy and hormonal therapy, and there is no standard follow-up treatment.…”

Section: Therapeutic Precismentioning

confidence: 99%

“…Apart from surgery, hormonal therapy, and radiotherapy, we introduced Chemo/Target therapy and immunotherapy associated with m6A. Above all, we collected the small molecule inhibitors that targeted m6A related proteins, which included ( Figure 3 ): 1 m6A modification, which could be inhibited by neplanocin A (NPC), Cycloleucine, and 3-Deazaadenosine ( Cayir, 2022 ); 2 METTL3, which was effectively repressed by STM2457 ( Yankova et al, 2021 ) and UZH1a ( Yanagi et al, 2022 ); 3 S-Adenosylhomocysteine (SAH), Antiviral agent 23/24 and STM2120 ( Yankova et al, 2021 ) was identified to inhibit the activity of METTL3/14 complex; 4 FB23 ( Huang et al, 2019 ), Rhein, Meclofenamic acid (MA) ( Huang et al, 2015 ), and Entacapone sodium salt could effectively repress FTO; 5 ALKBH5, whose potential inhibitor was IOX1 ( Li et al, 2016 ); 6 DC-Y3 and DC-Y13-27 were for YTHDF2 ( Wang et al, 2023 ); 7 SND1 was corresponding to Thymidine 3′,5′-disphosphate ( Jariwala et al, 2017 ); 8 IGF2BP2, which was restrained by CWI1-2 ( Weng et al, 2022 ); 9 MSI2, whose inhibitor was Romidepsin (FK228) ( Cayir, 2022 ; Zhu et al, 2022 ). …”

Section: Therapeutic Precismentioning

confidence: 99%

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Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review

Jin,

Sheng,

et al. 2023

Front. Genet.

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RNA modifications are mostly dynamically reversible post-transcriptional modifications, of which m6A is the most prevalent in eukaryotic mRNAs. A growing number of studies indicate that RNA modification can finely tune gene expression and modulate RNA metabolic homeostasis, which in turn affects the self-renewal, proliferation, apoptosis, migration, and invasion of tumor cells. Endometrial carcinoma (EC) is the most common gynecologic tumor in developed countries. Although it can be diagnosed early in the onset and have a preferable prognosis, some cases might develop and become metastatic or recurrent, with a worse prognosis. Fortunately, immunotherapy and targeted therapy are promising methods of treating endometrial cancer patients. Gene modifications may also contribute to these treatments, as is especially the case with recent developments of new targeted therapeutic genes and diagnostic biomarkers for EC, even though current findings on the relationship between RNA modification and EC are still very limited, especially m6A. For example, what is the elaborate mechanism by which RNA modification affects EC progression? Taking m6A modification as an example, what is the conversion mode of methylation and demethylation for RNAs, and how to achieve selective recognition of specific RNA? Understanding how they cope with various stimuli as part of in vivo and in vitro biological development, disease or tumor occurrence and development, and other processes is valuable and RNA modifications provide a distinctive insight into genetic information. The roles of these processes in coping with various stimuli, biological development, disease, or tumor development in vivo and in vitro are self-evident and may become a new direction for cancer in the future. In this review, we summarize the category, characteristics, and therapeutic precis of RNA modification, m6A in particular, with the purpose of seeking the systematic regulation axis related to RNA modification to provide a better solution for the treatment of EC.

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

Cited by 14 publications

References 36 publications

Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication

Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication

Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation

Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review

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