The identification of up-regulated ebv-miR-BHRF1-2-5p targeting MALT1 and ebv-miR-BHRF1-3 in the circulation of patients with multiple sclerosis

Wang, Y F; He, Di; Liang, Hongwei; Yang, Dan; Yue, Hui; Zhang, X M; Wang, R; Li, Bozhao; Yang, Hao; Liu, Y; Y, Chen; Duan, Yongzhong; Zhang, C Y; Chen, Xiaojia; Fu, Jin

doi:10.1111/cei.12954

Cited by 29 publications

(29 citation statements)

References 49 publications

(58 reference statements)

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“…These EBV-encoded miRNAs have also been shown to be important regulators for host-pathogen interactions and viral carcinogenesis (33). In different host cells, the expression profile of these viral miRNAs could be different and may serve as biomarkers for EBV-associated diseases (34)(35)(36)(37). Consistent with previous studies, which showed that the expression of miRNA from the miR-BHRF1 cluster was relatively restricted to lytic and latency III phases of EBV-infected B lymphoma cells (36,(38)(39)(40)(41)(42), we also observed that the miR-BHRF1 cluster is highly expressed in EBV-immortalized LCL cells and responds to LA treatment.…”

mentioning

confidence: 99%

Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth

Wei

Yin

et al. 2018

J Virol

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High plasma lactate is associated with poor prognosis of many malignancies, but its role in virally mediated cancer progression and underlying molecular mechanisms are unclear. Epstein-Barr virus (EBV), the first human oncogenic virus, causes several cancers, including B-cell lymphoma. Here, we report that lactate dehydrogenase A (LDH-A) expression and lactate production are elevated in EBV-immortalized B lymphoblastic cells, and lactic acid (LA; acidic lactate) at low concentration triggers EBV-infected B-cell adhesion, morphological changes, and proliferation and Moreover, LA-induced responses of EBV-infected B cells uniquely occurs in viral latency type III, and it is dramatically associated with the inhibition of global viral microRNAs, particularly the miR-BHRF1 cluster, and the high expression of ,, and genes. The introduction of miR-BHRF1-1 blocks the LA-induced effects of EBV-infected B cells. Thus, this may be a novel mechanism to explain EBV-immortalized B lymphoblastic cell malignancy in an LA microenvironment. The tumor microenvironment is complicated, and lactate, which is created by cell metabolism, contributes to an acidic microenvironment that facilitates cancer progression. However, how LA operates in virus-associated cancers is unclear. Thus, we studied how EBV (the first tumor virus identified in humans; it is associated with many cancers) upregulates the expression of LDH-A and lactate production in B lymphoma cells. Elevated LA induces adhesion and the growth of EBV-infected B cells by inhibiting viral microRNA transcription. Thus, we offer a novel understanding of how EBV utilizes an acidic microenvironment to promote cancer development.

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confidence: 99%

Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth

Wei

Yin

et al. 2018

J Virol

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“…miRs can have multiple targets as a result of binding not requiring 100% complementarity. 70 EBV miR-BHRF1-2-5p inhibits the MALT1 gene, which is a known regulator of immune homeostasis, 71 as well as the B-cell differentiation regulator/tumor suppressor gene PRDM1/BLIMP1, 72 but it was not previously known to bind PD-L1 or PD-L2. Using an integrated approach, we predicted and subsequently validated the interaction between EBV miR-BHRF1-2-5p with the 39UTRs of both PD-L1 and PD-L2.…”

Section: Discussionmentioning

confidence: 99%

EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2

Cristino

Nourse

West

et al. 2019

Blood

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This article reports a novel mechanism by which Epstein-Barr virus (EBV) microRNA (miRNA) plays a role to fine-tune the expression of LMP1-driven amplification of inhibitory checkpoint programmed death ligand 1 (PD-L1) and PD-L2 in EBV+ diffuse large B-cell lymphoma. Identification and understanding of the immune checkpoint regulation via miRNA may enable potential novel RNA-based therapies to emerge.

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“…Recently, EBV miR-BHRF1-2-5p has been reported to target mucosa-associated lymphoid tissue lymphoma transport protein 1 (MALT1), a key regulator of immune homeostasis (Wang et al, 2017). EBV miR-BART16 interferes with the type I IFN signaling pathway by directly targeting cAMP response element-binding protein (CREB)-binding protein (CREBBP), a key transcriptional coactivator in IFN signaling (Hooykaas et al, 2017).…”

Section: Ebv-encoded Mirnas Regulate the Immune Response By Targetingmentioning

confidence: 99%

An update: Epstein-Barr virus and immune evasion via microRNA regulation

Zuo

Yue

et al. 2017

Virol. Sin.

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Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans.To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs targeting both viral and host genes involved in the immune response. The miRNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4 + and CD8 + T cell response of infected cells. These reports strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host miRNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.

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The identification of up-regulated ebv-miR-BHRF1-2-5p targeting MALT1 and ebv-miR-BHRF1-3 in the circulation of patients with multiple sclerosis

Cited by 29 publications

References 49 publications

Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth

Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth

EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2

An update: Epstein-Barr virus and immune evasion via microRNA regulation

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