Epstein-Barr virus noncoding small RNA (EBER1) induces cell proliferation by up-regulating cellular mitochondrial activity and calcium influx

Ahmed, Waqar; Hassan, Zubaida; Abdelmowla, Yasmeen; Philip, Pretty S.; Shmygol, Anatoly; Khan, Gulfaraz

doi:10.1016/j.virusres.2021.198550

Cited by 4 publications

(6 citation statements)

References 67 publications

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“…Furthermore, following the G1/S transition, we observed a significant increase in the expression of S-phase markers in the wildtype EBER1 cells. This supports our earlier report that wildtype EBER1 prolongs S-phase in the lymphoid cells [13]. Abnormal gene expression is an initial trigger of cell cycle disorders, which eventually could lead to malignancies [47].…”

Section: Discussionsupporting

confidence: 91%

“…The direct impact of EBERs on enhancing growth potential was observed both in vitro in soft agar and in vivo in SCID mice [12]. Similarly, we have also demonstrated that EBER1 alone is capable of inducing cell growth in lymphoid cell lines [13].…”

Section: Introductionsupporting

confidence: 70%

“…Despite both direct and indirect evidence that EBERs could induce cell proliferation, which in turn could contribute to EBV-associated tumorigenesis [7,9,[11][12][13][14][15], the molecular mechanism remains poorly understood. Some of the proposed mechanisms of EBERsinduced cell proliferation suggest rather indirect mechanisms, such as inhibiting the activity of protein kinase R (PKR) [12].…”

Section: Introductionmentioning

confidence: 99%

“…Some of the proposed mechanisms of EBERsinduced cell proliferation suggest rather indirect mechanisms, such as inhibiting the activity of protein kinase R (PKR) [12]. Likewise, pathways involving mitochondrial activity and intracellular Ca 2+ have been suggested [13]. While most of the efforts to understand the mechanism of action of EBERs have focused on cellular dynamics, very few studies have examined the impact of the structure of EBERs on their function.…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Deleting Stem-Loop 1 of Epstein–Barr Virus-Encoded RNA 1 on Cell Proliferation

Hassan

Philip

Khan

2022

Viruses

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Epstein–Barr virus-encoded RNAs (EBERs) are two small, noncoding, structurally conserved transcripts, constitutively expressed at >106 copies per EBV-infected cell. They have been shown to drive cell growth. However, the mechanism(s) involved in EBER-induced proliferation is not clear. In this study, we investigated the molecular mechanisms and structural impact of EBER1. Sequences of EBER1 stem-loops (SL) 1, 3, and 4 were deleted, creating three mutants: ∆SL1, ∆SL3, and ∆SL4. These mutants were cloned into pHebo plasmids and expressed in Jurkat cell lines. Cells transfected with wildtype EBER1 and pHebo were used as controls. Cell proliferation was monitored by microscopy and flow cytometry. Microarray, qPCR, and Western blotting were used to investigate the cell cycle markers. We found significantly higher cell proliferation in wildtype EBER1 cells compared to pHebo, ∆SL1, and ∆SL3, but not ∆SL4 mutants. There was also significant upregulation of S-phase and G2/M phase markers in wildtype EBER1 and ∆SL4 mutant. Furthermore, CDT1, a factor for DNA replication, was upregulated in wildtype EBER1 and ∆SL4 mutant. However, in ∆SL1 mutant, CDT1 was significantly downregulated and translocated to the cytoplasm. These data indicate that the structure of EBER1 is important in cell proliferation.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Impact of Deleting Stem-Loop 1 of Epstein–Barr Virus-Encoded RNA 1 on Cell Proliferation

Hassan

Philip

Khan

2022

Viruses

Self Cite

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“…Building upon the foundation of this complex web of interactions, an in vitro study aimed to untangle the involvement of EBER1 and EBER2 by investigating the role and mechanism of EBER1-induced cell proliferation ( 56 ). Using cellular models, the researchers noted that EBER1 instigates cellular proliferation through the augmentation of mitochondrial activity and the influx of calcium ions ( Figure 1 ).…”

Section: The Elusive Escape Artist: Unraveling Ebv’s Art Of Immune Ev...mentioning

confidence: 99%

Epstein-Barr virus: the mastermind of immune chaos

Silva,

Alves,

Pontes

2024

Front. Immunol.

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The Epstein-Barr virus (EBV) is a ubiquitous human pathogen linked to various diseases, including infectious mononucleosis and multiple types of cancer. To control and eliminate EBV, the host’s immune system deploys its most potent defenses, including pattern recognition receptors, Natural Killer cells, CD8+ and CD4+ T cells, among others. The interaction between EBV and the human immune system is complex and multifaceted. EBV employs a variety of strategies to evade detection and elimination by both the innate and adaptive immune systems. This demonstrates EBV’s mastery of navigating the complexities of the immunological landscape. Further investigation into these complex mechanisms is imperative to advance the development of enhanced therapeutic approaches with heightened efficacy. This review provides a comprehensive overview of various mechanisms known to date, employed by the EBV to elude the immune response, while establishing enduring latent infections or instigate its lytic replication.

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Epstein–Barr virus noncoding RNA EBER1 promotes the expression of a ribosomal protein paralog to boost oxidative phosphorylation

Paudel,

Lee

2024

Journal of Medical Virology

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Epstein–Barr virus (EBV) is a highly successful pathogen that infects ~95% of the adult population and is associated with diverse cancers and autoimmune diseases. The most abundant viral factor in latently infected cells is not a protein but a noncoding RNA called EBV‐encoded RNA 1 (EBER1). Even though EBER1 is highly abundant and was discovered over forty years ago, the function of EBER1 has remained elusive. EBER1 interacts with the ribosomal protein L22, which normally suppresses the expression of its paralog L22‐like 1 (L22L1). Here we show that when L22 binds EBER1, it cannot suppress L22L1, resulting in L22L1 being expressed and incorporated into ribosomes. We further show that L22L1‐containing ribosomes preferentially translate mRNAs involved in the oxidative phosphorylation pathway. Moreover, upregulation of L22L1 is indispensable for growth transformation and immortalization of resting B cells upon EBV infection. Taken together, our results suggest that the function of EBER1 is to modulate host gene expression at the translational level, thus bypassing the need for dysregulating host gene transcription.

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Epstein-Barr virus noncoding small RNA (EBER1) induces cell proliferation by up-regulating cellular mitochondrial activity and calcium influx

Cited by 4 publications

References 67 publications

The Impact of Deleting Stem-Loop 1 of Epstein–Barr Virus-Encoded RNA 1 on Cell Proliferation

The Impact of Deleting Stem-Loop 1 of Epstein–Barr Virus-Encoded RNA 1 on Cell Proliferation

Epstein-Barr virus: the mastermind of immune chaos

Epstein–Barr virus noncoding RNA EBER1 promotes the expression of a ribosomal protein paralog to boost oxidative phosphorylation

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