Epigenetic Dysregulation of Epstein-Barr Virus Latency and Development of Autoimmune Disease

Niller, Hans Helmut; Wolf, Hans; Ay, Eva; Minárovits, János

doi:10.1007/978-1-4419-8216-2_7

Cited by 68 publications

(41 citation statements)

References 177 publications

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“…It is currently being correlated to autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren’s syndrome; these are complex disorders with a genetic background and the involvement of environmental factors, including viruses [7,8]. …”

Section: Introductionmentioning

confidence: 99%

Detection of a Specific Biomarker for Epstein-Barr Virus Using a Polymer-Based Genosensor

Balvedi

Castro

Madurro

et al. 2014

IJMS

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This paper describes methodology for direct and indirect detections of a specific oligonucleotide for Epstein-Barr virus (EBV) using electrochemical techniques. The sequence of oligonucleotide probe (EBV1) revealed a high sequence identity (100%) with the EBV genome. For the development of the genosensor, EBV1 was grafted to the platform sensitized with poly(4-aminothiophenol). After that, the hybridization reaction was carried out with the complementary target (EBV2) on the modified electrode surface using ethidium bromide as DNA intercalator. The oxidation peak currents of ethidium bromide increased linearly with the values of the concentration of the complementary sequences in the range from 3.78 to 756 μmol·L−1. In nonstringent experimental conditions, this genosensor can detect 17.32 nmol·L−1 (three independent experiments) of oligonucleotide target, discriminating between complementary and non-complementary oligonucleotides, as well as differentiating one-base mismatch, as required for detection of genetic diseases caused by point mutations. The biosensor also displayed high specificity to the EBV target with elimination of interference from mix (alanine, glucose, uric acid, ascorbic acid, bovine serum albumin (BSA), glutamate and glycine) and good stability (120 days). In addition, it was possible to observe differences between hybridized and non-hybridized surfaces through atomic force microscopy.

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Section: Introductionmentioning

confidence: 99%

Detection of a Specific Biomarker for Epstein-Barr Virus Using a Polymer-Based Genosensor

Balvedi

Castro

Madurro

et al. 2014

IJMS

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“…Several lines of evidence suggest that EBV infection also plays an important role in the pathophysiology of SLE, possibly by antigenic cross-reactivity between viral antigens and self-antigens, and/or the rescue of preexisting autoreactive B cells from apoptosis (15,34). LMP-1 mRNA is the most frequently detected latent EBV product in the increased population of EBVinfected memory B cells in the blood of SLE patients, although it is never detected in the blood of healthy individuals (13).…”

mentioning

confidence: 99%

Latency Type-Dependent Modulation of Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Expression by Type I Interferons in B Cells

Salamon

Ádori

Ujvári

et al. 2012

J Virol

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bWe report that type I interferons (IFNs) upregulate latent membrane protein 1 (LMP-1) expression by direct activation of the ED-L1 promoter in several Epstein-Barr virus (EBV)-carrying Burkitt's lymphoma lines. In EBV-infected primary B cells, IFN-␣ transiently upregulates LMP-1 mRNA, but not protein levels, followed by downregulation of both, suggesting a novel antiproliferative mechanism of type I IFNs. Furthermore, our results may explain the expression of LMP-1 in memory B cells of systemic lupus erythematosus patients. Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with a wide variety of neoplasms, including Burkitt's lymphoma (BL), nasopharyngeal carcinoma, posttransplant lymphoproliferative disease, and Hodgkin's disease. Only a subset of viral genes is transcribed from latent episomal EBV genomes in lymphoblastoid cell lines (LCLs) and in EBV-associated neoplasms. Besides EBV-encoded RNAs (EBERs) and BamHI-A transcripts, in type I latency only EBV nuclear antigen 1 (EBNA-1) is expressed, while in type III latency all six EBNAs and three EBVencoded latent membrane proteins (LMPs) are expressed. In type II latency, which is observed in Hodgkin T cell and NK cell lymphomas, in the lymphoid tissues of healthy virus carriers and infectious mononucleosis patients one or all of the LMPs are expressed in addition to the type I latency gene products (39). LMP-1 plays a central role in EBV biology, since it acts in part as a constitutively active CD40 receptor analog and is essential for B cell proliferation and transformation by EBV (24). In type III latency, EBNA-2 is the major transactivator of the LMP promoters, while in type II latency, depending on the cellular context, different cytokines , are responsible for the activation of LMP-1 transcription (20,26,27,28).Type I interferons (IFNs) are produced in relatively large amounts in response to pathogen sensing by the innate immune system (46). In addition to their direct antiviral activities, these proteins also have antiproliferative and immunomodulatory properties. Consequently, type I IFNs find diverse clinical application in the treatment of certain forms of cancer, as well as in the therapy of viral infections or immunological disorders (31). On the other hand, type I IFNs have a major pathophysiological role in human diseases, such as systemic lupus erythematosus (SLE), with characteristic high IFN-␣ levels (46). Several interactions have been described between EBV and the type I IFN system. EBV virions and/or EBER1 (secreted in complex with lupus erythematosus-associated antigen or added exogenously in an in vitro-synthesized form) induces type I IFN production in several cell types, including B cells and plasmacytoid dendritic cells (21,25,38) For initial experiments, we chose the highly IFN-␣-sensitive, EBV-positive BL line Daudi (29), in which IFN-␣ treatment inhibits cell proliferation and concomitantly induces plasmacytoid differentiation (8). Daudi cells were treated with different concentrations of IFN-␣, IFN-␤, and IFN-␥...

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“…Among environmental factors considerable evidence has linked past EpsteinBarr virus (EBV) infection to an increased risk of MS, and, since a complete silencing of the EBV genome in memory B cells is under epigenetic control via DNA methylation and histone tail modifi cations, some authors have suggested that an epigenetic dysregulation of the EBV latency might contribute to the development of MS and other autoimmune diseases (Niller et al 2011 ).…”

Section: Epigenetics Of Multiple Sclerosismentioning

confidence: 99%

Epigenetics of Autoimmune Diseases

Coppedè

Migliore

2014

Molecular Mechanisms and Physiology of Disease

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This chapter provides several examples of epigenetic deregulation in autoimmune diseases, a heterogeneous group of human conditions characterized by a deregulated immune response against the body own organs and tissues. Early studies based on the candidate gene approach have been flanked by genomewide screenings in the last few years, revealing global changes in DNA methylation or histone tail modifications, as well as deregulated methylation and/or expression of hundreds of genes and microRNAs in cells from patients affected by those disorders. This chapter will focus on epigenetic deregulations observed in systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, psoriasis, multiple sclerosis, systemic sclerosis, and autoimmune thyroid diseases, even though epigenetic modifications are increasingly being observed in many other autoimmune diseases. By contrast, only a few environmental factors have been shown or suspected to induce the observed epigenetic changes. Epigenetic drugs and RNA silencing experiments have often reversed autoimmune disease-like phenotypes in rodents or cell cultures, leading researchers to debate on their potential use in the treatment of these human conditions

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Epigenetic Dysregulation of Epstein-Barr Virus Latency and Development of Autoimmune Disease

Cited by 68 publications

References 177 publications

Detection of a Specific Biomarker for Epstein-Barr Virus Using a Polymer-Based Genosensor

Detection of a Specific Biomarker for Epstein-Barr Virus Using a Polymer-Based Genosensor

Latency Type-Dependent Modulation of Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Expression by Type I Interferons in B Cells

Epigenetics of Autoimmune Diseases

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