trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1.

Reisman, David; Sugden, Bill

doi:10.1128/mcb.6.11.3838

Cited by 349 publications

(298 citation statements)

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“…This may be due to enhanced transcription of oriP-containing DNA by EBNA-1. 17,18 The activation of viral gene transcription by EBNA-1 is the third advantage of the EBV replicon vector. Thus, high expression of a transgene in an EBV replicon vector in rodent cells may be mediated both by nuclear retention of the gene and by transcription activation.…”

Section: Discussionmentioning

confidence: 99%

Sustained transgene expression in vitro and in vivo using an Epstein–Barr virus replicon vector system combined with HVJ liposomes

et al. 1998

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For long-term gene expression in tissues, we constructed chromosomally in BHK-21 cells. In human cells, transforman Epstein-Barr virus (EBV) replicon-based plasmid, pEB, ation was five to 20 times more efficient with pEBc than containing the latent viral DNA replication origin (oriP) and with pcDNA3, and 18-35% of the introduced EBV replicon EBV nuclear antigen-1 (EBNA-1). When pEB was transplasmid was replicated autonomously. The luciferase gene ferred to human cells (HeLa-S3, HEK 293 and FS 3) and or lacZ gene was introduced into mouse liver using HVJrodent cells (BHK-21) using HVJ-cationic liposomes, AVE liposomes. Luciferase gene expression was observed luciferase expression was observed in those cells for at for at least 35 days in cells transfected with pEBActLuc, least 10 days. Luciferase activity was two to 10 times whereas it was not detected on day 14 in cells transfected higher in those cell lines on and after day 3 post-transfecwith pActLuc, which lacks the EBV sequence. By the transtion of pEBActLuc compared with plasmids without the fer of pEBActNlacF, the lacZ gene expression rate in hepa-EBV replicon sequence. Southern blot analysis showed tocytes was approximately 35 and 12% on days 7 and that the pEB vector luciferase gene was maintained extra-35, respectively.

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Section: Discussionmentioning

confidence: 99%

Sustained transgene expression in vitro and in vivo using an Epstein–Barr virus replicon vector system combined with HVJ liposomes

et al. 1998

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“…Therefore, immunosuppressive therapy [13], hereditary immunodeficiencies [14] or immunocompromising HIV-infection [15] may lead to uncontrolled EBV reactivation and disease. EBV nuclear antigen 1 (EBNA-1) is a latent antigen that is invariably expressed in all EBV-infected proliferating cells [16] and associated malignancies [17], being crucial for viral persistence by acting as replication and transcription factor [18], without viral particle formation. EBNA-1 is an immunodominant latent target of EBVspecific CD4 1 T cells [19,20].…”

Section: Introductionmentioning

confidence: 99%

Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets

Guerreiro

Letsch

et al. 2010

Eur J Immunol

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EBV infection leads to life-long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease-free as a result of effective control by T cells. EBV-specific IFN-c-producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN-c alone is insufficient to assess the quantity and quality of a T-cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF-1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV-reactive T cells in healthy virus carriers are indeed IL-2-and/or TNF-producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV-specific CD4 1 and CD8 1 T cells retained a CC-chemokine receptor 7 (CCR7)-positive memory phenotype. Based on their cytokine profiles, six different EBV-specific T-cell subsets could be distinguished with TNF-single or TNF/IL-2-double producing cells expressing the highest CCR7 levels resembling earlydifferentiated memory T cells. Our study delineates the memory T-cell profile of a protective immune response and provides a basis for analyzing T-cell responses in EBVassociated diseases.Key words: BM . EBV . Immune monitoring . Multifunctional T cells . T-cell memory IntroductionEBV is a human gamma herpesvirus that is widespread in all human populations. Following oral transmission, EBV replicates in the oropharyngeal epithelial cells and infects mucosal B cells, leading to a life-long persistence in the memory B-cell pool [1,2]. The primary infection occurs usually during childhood and is often asymptomatic; however, infection is manifested as acute infectious mononucleosis in a subset of patients [3]. Despite the relatively benign course in most carriers, EBV reactivation is considered as a risk-factor both for malignant transformation and autoimmune diseases. The ability of the EBV encoded protein 1566LMP-1 to induce T-cell-independent immunoglobulin class switch DNA recombination and BAFF, a B-cell activating factor, that rescues self-reactive T cells, is considered to play an important role in the pathogenesis of EBV-related autoimmune and lymphoproliferative disease [4]. EBV is causatively linked to nasopharyngeal carcinoma and B-cell malignant diseases such as endemic Burkitt's lymphoma, Hodgkin's lymphoma and posttransplant lymphoproliferative diseases (PTLD) [5][6][7]. Recent data suggest that EBV is associated with various autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and primary Sjögren's syndrome [8,9]. Chronic active EBV infection can also cause Chronic Fatigue Syndrome, which is frequently associated with autoimmune thyreoiditis [10].The EBV cycle has two distinct stages, the latent infection where the genome is maintained at a constant copy number per cell and limited regions of the genome are expressed and the lytic cycle w...

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“…Initial genetic dissections of EBV identified one viral protein, Epstein-Barr Nuclear Antigen 1 (EBNA1), and one region of the viral genome, termed oriP, as being necessary and sufficient for replication of the viral plasmid (Yates, Warren et al 1984) (Lupton and Levine 1985;Reisman, Yates et al 1985), (Reisman and Sugden 1986). oriP is composed of two separable cis elements, the Family of Repeats (FR) and the Dyad Symmetry element (DS) (Baer, Bankier et al 1984;Reisman, Yates et al 1985), which both contain binding sites for EBNA1 in vitro (Rawlins, Milman et al 1985) (Harrison, Fisenne et al 1994), and in vivo (Hsieh, Camiolo et al 1993), (Niller, Glaser et al 1995) (Figure 1).…”

Section: Cis Elements Of Ebv That Contribute To Dna Replicationmentioning

confidence: 99%

“…FR is composed of 21 imperfect copies of a 30bp repeat and contains 20 high affinity EBNA1-binding sites (Figure 1). When FR is bound by EBNA1, it both serves as a transcriptional enhancer of promoters in cis up to 10kb away (Reisman and Sugden 1986), (Yates 1988), (Sugden and Warren 1989), (Wysokenski and Yates 1989), (Gahn and Sugden 1995), (Kennedy and Sugden 2003;Altmann, Pich et al 2006), and contributes to the nuclear retention and faithful maintenance of FR-containing plasmids (Langle-Rouault, Patzel et al 1998), (Kirchmaier and Sugden 1995), (Wang, Lindner et al 2006) (Nanbo, Sugden et al submitted). The efficient partitioning of oriP plasmids is also likely attributable to FR.…”

Section: Cis Elements Of Ebv That Contribute To Dna Replicationmentioning

confidence: 99%

The plasmid replicon of Epstein–Barr virus: Mechanistic insights into efficient, licensed, extrachromosomal replication in human cells

Lindner

Sugden

2007

Plasmid

103

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The genome of Epstein-Barr Virus (EBV) and plasmid derivatives of it are among the most efficient extrachromosomal replicons in mammalian cells. The latent origin of plasmid replication (oriP), when supplied with the viral Epstein-Barr Nuclear Antigen 1 (EBNA1) in trans, provides efficient duplication, partitioning and maintenance of plasmids bearing it. In this review, we detail what is known about the viral cis and trans elements required for plasmid replication. In addition, we describe how the cellular factors that EBV usurps are used to complement the functions of the viral constituents. Finally, we propose a model for the sequential assembly of an EBNA1-dependent origin of DNA synthesis into a pre-Replicative Complex (pre-RC), which functions by making use only of cellular enzymatic activities to carry out the replication of the viral plasmid. KeywordsoriP; EBNA1; EBV; origin; DS; Rep* General BackgroundEpstein-Barr Virus (EBV), a member of the herpesvirus family, is a surprisingly successful parasite, as are other human members of this family of viruses. It establishes a persistent, lifelong infection in greater than 90% of the world's population (Fields, Knipe et al. 2006). Primary infection by EBV causes infectious mononucleosis in some, usually adolescent people (Evans, Niederman et al. 1968). The latent cycle of the virus that follows infection is usually asymptomatic in the host, however in a small fraction of infected people, EBV contributes to several cancers including Burkitt's lymphoma, some T-cell lymphomas, Hodgkin's disease, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma, and gastric carcinoma. EBV was the first human virus to be classified as a tumor virus (reviewed in Chapter 75 of (Fields, Knipe et al. 2006)) and has been studied because of its association with these diseases. EBV, in addition, has also served as a model to study DNA replication in human cells because of it's ability both to maintain its genome as an extrachromosomal replicon in infected B-cells, and to appropriate the cellular DNA replication machinery needed for its licensed replication.* To whom correspondence should be addressed: 1400 University Ave, Madison, WI 53706, Phone: 608.262.6697, Fax: 608.262.2824, Email: sugden@oncology.wisc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Cis Elements of EBV that Contribute to DNA ReplicationThe genome of EBV is approximately 165kbp (Bloss and Sugden 1994) and resides as a nucleosome-coated nuclear plasmid in infected cells (Wensing and Farrell 2000), (Shaw, Levinger et al. 1979)...

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trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1.

Cited by 349 publications

References 47 publications

Sustained transgene expression in vitro and in vivo using an Epstein–Barr virus replicon vector system combined with HVJ liposomes

Sustained transgene expression in vitro and in vivo using an Epstein–Barr virus replicon vector system combined with HVJ liposomes

Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets

The plasmid replicon of Epstein–Barr virus: Mechanistic insights into efficient, licensed, extrachromosomal replication in human cells

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