Epstein–Barr virus particles induce centrosome amplification and chromosomal instability

Shumilov, Anatoliy; Tsai, Ming Han; Schlosser, Yvonne T; Kratz, Anne Sophie; Bernhardt, Katharina; Fink, Susanne; Mizani, Tuba; Lin, Xiaochen; Jauch, Anna; Mautner, Josef; Kopp‐Schneider, Annette; Feederle, Regina; Hoffmann, Ingrid; Delecluse, Henri Jacques

doi:10.1038/ncomms14257

Cited by 71 publications

(73 citation statements)

References 68 publications

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“…LMP1-associated genomic instability may also result from telomerase activation and DNA damage response (DDR) inhibition [69, 77]. Intriguingly, EBV tegument protein BNRF1 could also induce centrosome amplification and further chromosome instability during lytic infection, suggesting that EBV viral particles may be sufficient to modify host chromosome without the establishment of latent infection [78]. …”

Section: Molecular Biology Of Ebv-mediated B-cell Lymphomasmentioning

confidence: 99%

Current Progress in EBV-Associated B-Cell Lymphomas

Pei

Lewis

2017

Advances in Experimental Medicine and Biology

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Epstein-Barr virus (EBV) was the first human tumor virus discovered more than 50 years ago. EBV-associated lymphomagenesis is still a significant viral-associated disease as it involves a diverse range of pathologies, especially B-cell lymphomas. Recent development of high-throughput next-generation sequencing technologies and in vivo mouse models have significantly promoted our understanding of the fundamental molecular mechanisms which drive these cancers and allowed for the development of therapeutic intervention strategies. This review will highlight the current advances in EBV-associated B-cell lymphomas, focusing on transcriptional regulation, chromosome aberrations, in vivo studies of EBV-mediated lymphomagenesis, as well as the treatment strategies to target viral-associated lymphomas.

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Section: Molecular Biology Of Ebv-mediated B-cell Lymphomasmentioning

confidence: 99%

Current Progress in EBV-Associated B-Cell Lymphomas

Pei

Lewis

2017

Advances in Experimental Medicine and Biology

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“…EBV‐infected cells express viral oncogenes that induce cell transformation. EBV latent and lytic genes can cause chromosomal instability . As seen in many cancers, multiple genetic alterations are present in NPC.…”

Section: Introductionmentioning

confidence: 99%

“…EBV latent and lytic genes can cause chromosomal instability. [2][3][4][5][6] As seen in many cancers, multiple genetic alterations are present in NPC. Early studies identified the losses of chromosomes 3p and 9p as early events in the development of NPC.…”

Section: Introductionmentioning

confidence: 99%

Targeted sequencing of cancer‐related genes in nasopharyngeal carcinoma identifies mutations in the TGF‐β pathway

et al. 2019

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Approximately, 25% of nasopharyngeal carcinoma (NPC) patients develop recurrent disease. NPC may involve relatively few genomic alterations compared to other cancers due to its association with Epstein‐Barr virus (EBV). We envisioned that in‐depth sequencing of tumor tissues might provide new insights into the genetic alterations of this cancer. Thirty‐three NPC paired tumor/adjacent normal or peripheral blood mononuclear cell samples were deep‐sequenced (>1000×) with respect to a panel of 409 cancer‐related genes. Newly identified mutations and its correlation with clinical outcomes were evaluated. Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF‐κB, and TGF‐β pathways. In addition, patients harbored CNV among 409 cancer‐related genes and missense mutations in TGF‐β/SMAD signaling were associated with poor overall survival and poor recurrence‐free survival, respectively. The CNV events were correlated with plasma EBV copies, while mutations in TGFBR2 and SMAD4 abrogate SMAD‐dependent TGF‐β signaling. Functional analysis revealed that the new TGFBR2 kinase domain mutants were incapable of transducing the signal, leading to failure of phosphorylation of SMAD2/3 and activation of downstream TGF‐β‐mediated cell growth arrest. This study provides evidence supporting CNV and dysregulated TGF‐β signaling contributes to exacerbating the NPC pathogenesis.

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“…Also, EBV lytic genes BZLF1 , BGLF4 and BGLF5 can induce genome instability. Most notably, one latest research reported EBV lytic replication had a marked influence on the genetic stability and identified a new mechanism in EBV induced cancer . EBV virions that generate in the process of lytic replication can induce aneuploidy and centrosome amplification, associated with chromosomal instability, thereby conferring a risk to non‐replicating cells and for development of tumors.…”

Section: Oxidative Stress and Ebv Lytic Reactivationmentioning

confidence: 99%

The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications

Luo

et al. 2017

Intl Journal of Cancer

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Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a "double-edged sword" to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers.

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Epstein–Barr virus particles induce centrosome amplification and chromosomal instability

Cited by 71 publications

References 68 publications

Current Progress in EBV-Associated B-Cell Lymphomas

Current Progress in EBV-Associated B-Cell Lymphomas

Targeted sequencing of cancer‐related genes in nasopharyngeal carcinoma identifies mutations in the TGF‐β pathway

The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications

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