Reframing Burkitt lymphoma: virology not epidemiology defines clinical variants

Rochford, Rosemary

doi:10.21037/aol-21-18

Cited by 12 publications

(6 citation statements)

References 104 publications

(155 reference statements)

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“…Burkitt lymphoma is primarily associated with a type I latency pattern, meaning EBNA1 is the main protein expressed [ 37 ]. Indeed, there is some evidence that EBNA1 may be involved in the pathogenesis of Burkitt lymphoma [ 155 ]. For example, EBNA1 knockout using the transcription activator-like effector nuclease E1TN resulted in the death of cells infected by EBV.…”

Section: Ebv and Oncogenesismentioning

confidence: 99%

EBV and Lymphomagenesis

Sausen

Basith

Muqeemuddin³

2023

Cancers

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The clinical significance of Epstein–Barr virus (EBV) cannot be understated. Not only does it infect approximately 90% of the world’s population, but it is also associated with numerous pathologies. Diseases linked to this virus include hematologic malignancies such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Burkitt lymphoma, primary CNS lymphoma, and NK/T-cell lymphoma, epithelial malignancies such as nasopharyngeal carcinoma and gastric cancer, autoimmune diseases such as multiple sclerosis, Graves’ disease, and lupus. While treatment for these disease states is ever evolving, much work remains to more fully elucidate the relationship between EBV, its associated disease states, and their treatments. This paper begins with an overview of EBV latency and latency-associated proteins. It will then review EBV’s contributions to select hematologic malignancies with a focus on the contribution of latent proteins as well as their associated management.

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Section: Ebv and Oncogenesismentioning

confidence: 99%

EBV and Lymphomagenesis

Sausen

Basith

Muqeemuddin³

2023

Cancers

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“…After initial infection, the virus enters a latent infection of B lymphocytes and persists throughout the lifetime of the host [ 2 ]. EBV is associated with a number of human cancers (e.g., Hodgkin's lymphoma [ 3 ], Burkitt lymphoma [ 2 ], and nasopharyngeal carcinoma [ 4 ]) and autoimmune disorders (e.g., systemic lupus erythematosus (SLE) and multiple sclerosis (MS)). The causal role of EBV in autoimmune disease has become clearer with recent molecular and epidemiological studies [ 5 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome

Viel,

Parameswaran,

Donmez

et al. 2024

BMC Genomics

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Background There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. Results In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. Conclusions This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.

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“…BL presents within the abdominal region, lymph nodes, and can also be extranodal. The third variant is HIV-associated BL (ID-BL), which is diagnosed at the early stage of HIV infection and prior to CD4+ T-cell decreases [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…Most endemic BLs are associated with EBV, which suggests that the virus has a direct role in lymphoma pathogenesis. About 95% of eBL detect EBV [ 28 ], whereas only about 10–30% of EBV is detected in sBL [ 21 ], and 20–40% of EBV positives are detected in ID-BL [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Worldwide Prevalence of Epstein–Barr Virus in Patients with Burkitt Lymphoma: A Systematic Review and Meta-Analysis

et al. 2023

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Burkitt lymphoma (BL) is a form of B-cell malignancy that progresses aggressively and is most often seen in children. While Epstein–Barr virus (EBV) is a double-stranded DNA virus that has been linked to a variety of cancers, it can transform B lymphocytes into immortalized cells, as shown in BL. Therefore, the estimated prevalence of EBV in a population may assist in the prediction of whether this population has a high risk of increased BL cases. This systematic review and meta-analysis aimed to estimate the prevalence of Epstein–Barr virus in patients with Burkitt lymphoma. Using the appropriate keywords, four electronic databases were searched. The quality of the included studies was assessed using the Joanna Briggs Institute’s critical appraisal tool. The results were reported as percentages with a 95% confidence interval using a random-effects model (CI). PROSPERO was used to register the protocol (CRD42022372293), and 135 studies were included. The prevalence of Epstein–Barr virus in patients with Burkitt lymphoma was 57.5% (95% CI: 51.5 to 63.4, n = 4837). The sensitivity analyses demonstrated consistent results, and 65.2% of studies were of high quality. Egger’s test revealed that there was a significant publication bias. EBV was found in a significantly high proportion of BL patients (more than 50% of BL patients). This study recommends EBV testing as an alternative for predictions and the assessment of the clinical disease status of BL.

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Reframing Burkitt lymphoma: virology not epidemiology defines clinical variants

Cited by 12 publications

References 104 publications

EBV and Lymphomagenesis

EBV and Lymphomagenesis

Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome

Worldwide Prevalence of Epstein–Barr Virus in Patients with Burkitt Lymphoma: A Systematic Review and Meta-Analysis

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