Is the Epstein–Barr virus EBNA-1 protein an oncogen?

Schulz, Thomas F.; Cordes, Susann

doi:10.1073/pnas.0812575106

Cited by 22 publications

(21 citation statements)

References 19 publications

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“…[13] In cases where LMP-1 is absent, the loss of A20 may be an alternative mechanism of NFκB pathway activation as has been recently described in a subset of AIDS-related lymphomas. [14]…”

Section: Ebv and Lymphomagenesismentioning

confidence: 99%

EBV-associated lymphomas in adults

Roschewski

Wilson

2012

Best Practice & Research Clinical Haematology

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Epstein-Barr virus (EBV) is a ubiquitous γ-herpes virus that infects most people but results in life-threatening diseases in only a small subset. Persons who are unable to maintain the virus in its latent state can develop uncontrolled EBV-driven lymphoproliferative disorders and lymphomas. EBV-associated lymphomas are well-characterized in patients with known defects in cellular immunity as occurs post-transplantation or HIV/AIDS but are increasingly recognized in patients without overt immunodeficiencies. Improved understanding of the biology of these lymphomas and the role EBV plays in lymphomagenesis offers the opportunity for improved therapies targeted at important signaling pathways and immunotherapy specific against EBV viral antigens.

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“…[13] In cases where LMP-1 is absent, the loss of A20 may be an alternative mechanism of NFκB pathway activation as has been recently described in a subset of AIDS-related lymphomas. [14]…”

Section: Ebv and Lymphomagenesismentioning

confidence: 99%

EBV-associated lymphomas in adults

Roschewski

Wilson

2012

Best Practice & Research Clinical Haematology

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“…Interestingly, Fp is activated during the lytic cycle (2). EBNA-1 is essential for replication and stable persistence of episomes in EBV-infected proliferating cells and it is the only EBV encoded antigen that is consistently expressed in all EBV-associated tumors (9). EBNA-1 contains two major functional domains - a C-terminal viral DNA binding domain at OriP, and an N-terminal host-chromosome tethering domain.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, EBNA-1 expression increases metastasis in nude mice through blocking the activity of metastasis suppressor protein, Nm23-H1 (13). In addition, mice carrying an EBNA-1 trans-gene under control of the Ig heavy chain enhancer develop lymphomas (9). Furthermore, EBNA-1 may modulate its anti-apoptotic function by interacting with the host deubiquitinating enzyme HAUSP (14).…”

Section: Introductionmentioning

confidence: 99%

“…However, in EBV infected cells EBNA-1 can efficiently block the interaction between HAUSP and p53 resulting in ubiquitin-proteasome mediated degradation of p53 (5, 14). It should be noted that the effects of EBNA-1 on apoptosis are not only restricted to the regulation of p53 expression levels but also disrupts PML nuclear bodies in NPC cells (15), and leads to genomic instability by activating the recombinase-activating genes RAG-1 and RAG-2 (9). Although, it has long been thought that EBNA-1 expressing cells escape from cell-mediated immune system by blocking the MHC class I-restricted presentation, recent studies show that EBNA-1 can be presented to both CD4 and CD8-positive T cells.…”

Section: Introductionmentioning

confidence: 99%

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Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes

Saha

Robertson²

2011

Clinical Cancer Research

130

129

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Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus that establishes a life-long asymptomatic infection in immunocompetent hosts. It is also found to be frequently associated with a broad spectrum of B-cell lymphomas predominantly seen in immunodeficient patients. In spite of many resemblances, these EBV-linked lymphoproliferative disorders display heterogeneity at the clinical as well as the molecular level. Moreover, EBV-associated lymphoproliferative diseases differ in their differential expression patterns of the EBV-encoded latent antigens which are directly related to their interactions with the host. EBV-driven primary B-cell immortalization is linked to the cooperative functions of these latent proteins that are critical for perturbing many important cell-signaling pathways maintaining B-cell proliferation. Additionally, it is used as a surrogate model to explore the underlying mechanisms involved in the development of B-cell neoplasms. Recent discoveries have revealed that a number of sophisticated mechanisms exploited by EBV during cancer progression. This will be instrumental in the design of novel approaches for therapeutic interventions against EBV associated B-cell lymphomas. This review limits the discussion to the biology and pathogenesis of EBV associated B-cell lymphomas and the related clinical implications.

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“…Epstein-Barr virus, the causative agent of infectious mononucleosis, is associated with the occurrence of malignancies such as Burkitt's lymphoma and nasopharyngeal carcinoma, 4 and its EBNA 1 protein has been strongly implicated as a contributing factor to such events. 5 By contrast, episomal vector systems based on chromosomal elements have been developed, in which the incorporation of a scaffold matrix attachment region (S/MAR) replaces the need for any virally encoded protein to ensure episomal replication and maintenance. S/MARs are DNA sequences, which bind chromatin to the nuclear matrix.…”

Section: Introductionmentioning

confidence: 99%

Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage

et al. 2010

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Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage SP Wong, O Argyros, C Coutelle and RP HarbottleThe ideal gene therapy vector should enable persistent expression without the limitations of safety and reproducibility. We previously reported that a prototype plasmid vector, containing a scaffold matrix attachment region (S/MAR) domain and the luciferase reporter gene, showed transgene expression for at least 6 months following a single administration to MF1 mice. Following partial hepatectomy of the animals, however, we found no detectable vector replication and subsequent propagation in vivo. To overcome this drawback, we have now developed an in vivo liver selection strategy by which liver cells transfected with an S/MAR plasmid are provided with a survival advantage over non-transfected cells. This allows an enrichment of vectors that are capable of replicating and establishing themselves as extra-chromosomal entities in the liver. Accordingly, a novel S/MAR plasmid encoding the Bcl-2 gene was constructed; Bcl-2 expression confers resistance against apoptosis-mediated challenges by the Fas-activating antibody Jo2. Following hydrodynamic delivery to the livers of mice and frequent Jo2 administrations, we demonstrate that this Bcl-luciferase S/MAR plasmid is indeed capable of providing sustained luciferase reporter gene expression for over 3 months and that this plasmid replicates as an episomal entity in vivo. These results provide proof-of-principle that S/MAR vectors are capable of preventing transgene silencing, are resistant to integration and are able to confer mitotic stability in vivo when provided with a selective advantage.

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Is the Epstein–Barr virus EBNA-1 protein an oncogen?

Cited by 22 publications

References 19 publications

EBV-associated lymphomas in adults

EBV-associated lymphomas in adults

Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes

Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage

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