Epstein–Barr virus in the multiple sclerosis brain: a controversial issue—report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria

Recent epidemiological and immunological studies provide evidence for an association between Epstein–Barr virus infection and multiple sclerosis, suggesting a role of Epstein–Barr virus infection in disease induction and pathogenesis. A key question in this context is whether Epstein–Barr virus-infected B lymphocytes are present within the central nervous system and the lesions of patients with multiple sclerosis. Previous studies on this topic provided highly controversial results, showing Epstein–Barr virus reactivity in B cells in the vast majority of multiple sclerosis cases and lesions, or only exceptional Epstein–Barr virus-positive B cells in rare cases. In an attempt to explain the reasons for these divergent results, a workshop was organized under the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which is presented here. This report summarizes the current knowledge of Epstein–Barr virus biology and shows that Epstein–Barr virus infection is highly complex. There are still major controversies, how to unequivocally identify Epstein–Barr virus infection in pathological tissues, particularly in situations other than Epstein–Barr virus-driven lymphomas or acute Epstein–Barr virus infections. It further highlights that unequivocal proof of Epstein–Barr virus infection in multiple sclerosis lesions is still lacking, due to issues related to the sensitivity and specificity of the detection methods

Epstein-Barr Virus Infection and Sporadic Breast Cancer Risk: A Meta-Analysis

BACKGROUND: A large number of epidemiological studies have evaluated the association between Epstein-Barr virus infection and breast carcinoma risk but results have been inconsistent. METHODOLOGY: Research using the polymerase chain reaction technique for detecting the Epstein-Barr virus was selected; 24 studies and 1535 cases were reviewed. Information on the study populations, sample types, publication calendar period and histological types of breast carcinoma were collected. An unconditional logistic regression model was used to analyze potential parameters related to the Epstein-Barr virus prevalence. A Kappa test was used to evaluate the consistency in detecting different Epstein-Barr virus DNA regions. Nine studies that included control groups and 1045 breast cancer cases were adopted in this meta-analysis. CONCLUSIONS: We found that 29.32% of the patients with breast carcinoma were infected with the Epstein-Barr virus. The prevalence of Epstein-Barr was highest in Asia (35.25%) and lowest in the USA (18.27%). Statistical analysis revealed a trend that showed lobular breast carcinoma might have the strongest association with Epstein-Barr virus infection. This meta-analysis showed a significant increase in breast malignancy risk in patients testing positive for the Epstein-Barr virus (OR = 6.29, 95% CI = 2.13-18.59). This result suggests that an Epstein-Barr virus infection is statistically associated with increased breast carcinoma risk

Low prevalence of Epstein–Barr virus in incident gastric adenocarcinomas from the United Kingdom

Epstein–Barr virus has been associated with a proportion of typical gastric adenocarcinomas. Here we report that the prevalence of Epstein–Barr virus in gastric adenocarcinomas from the United Kingdom is one of the lowest in the World. Gastric adenocarcinoma is another tumour whose association with Epstein–Barr virus varies with the population studied

Profil Imunopositivitas Protein Ebv Pada Penderita Karsinoma Nasofaring Dan Individu Sehat Berisiko

Latar Belakang: Analisis immunoblot digunakan untuk mendeteksi protein Epstein –Barr pada serum darah penderita karsinoma nasofaring dan individu sehat berisiko.Tujuan: Mengetahui perbedaan imunopositivitas protein Epstein-Barr Virus antara penderita karsinoma nasofaring dengan individu sehat berisiko.Metode: Penelitian observasional dengan case-control design, menggunakan sampel darah 20 penderita karsinoma nasofaring dan kontrol yang terdiri dari 20 individu sehat berisiko. Imunopositivitas Protein Epstein-Barr dianalisis denganimmunoblot.Hasil: Uji Mann-Whitney menghasilkan imunopositivitas protein-protein yang memberikan perbedaan bermakna secara statistik, yaitu : VCA-p18 (p=0.041), VCA-p40 (p=0.035) dan EA-p47/54 (p=0.009) dan tidak bermakna secara statistikyaitu : ZEBRA(0.140) , EBNA1 (0.540), TK(0.713), dan DNAse (0.740)Kesimpulan: Terdapat perbedaan imunopositivitas protein VCA-p18, VCA-p40 dan EA-p47/54 Epstein-Barr Virus dan tidak terdapat perbedaan imunopositivitas protein ZEBRA, EBNA1, TK, dan DNAse Epstein-Barr Virus antara penderitakarsinoma nasofaring dengan individu sehat berisiko

Epstein-barr Virus Infection And Gastric Carcinoma In São Paulo, Brazil

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and most people have serological evidence of previous viral infection at adult age. EBV is associated with infectious mononucleosis and human cancers, including some lymphomas and gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like gastric carcinoma, the virus was also found in conventional adenocarcinomas. In the present study, 53 gastric carcinomas diagnosed in São Paulo State, Brazil, were evaluated for EBV infection by non-isotopic in situ hybridization with a biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA) directed to the viral transcript EBER-I, which is actively expressed in EBV latently infected cells. EBV infection was found in 6 of 53 (11.32%) gastric carcinomas, mostly from male patients (66.7%), with a mean age of 59 years old. Most EBV-positive tumors were in gastric antrum. Two EBV-positive tumors (33.3%) were conventional adenocarcinomas, whereas four (66.7%) were classified as lymphoepithelioma-like carcinomas. EBV infection in gastric carcinomas was reported elsewhere in frequencies that range from 5.6% (Korea) up to 18% (Germany). In Brazil, a previous work found EBV infection in 4 of 80 (5%) gastric carcinomas, whereas another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of Brazilians of Japanese origin or not, respectively. 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Interleukin-10 Promotes cell proliferation in Epstein-Barr infected B cells through activation of Ras/ERK and phosphorylation of c-Myc

Epstein-Barr virus is a human herpes virus that in conjunction with Malaria is responsible for endemic Burkitt's lymphoma, a B-cell cancer. The main distinguishing characteristic of Burkitt's lymphoma is a constitutively active c-Myc protein. The transcription factor c-Myc is considered to be a proto-oncogene, which is responsible for cell proliferation and differentiation. The activation of c-Myc leads to the production of cyclin D1 and Cdk4, which promote the G1 to S transition of the cell cycle. The activation of c-Myc is dependent on the Ras/ERK pathway, which can be activated by extracellular signals in the form of cytokines. Interleukin-10 is a cytokine that is produced by Burkitt's lymphoma cells and may act as an autocrine growth factor for the cancer. It may be possible that the Ras/ERK pathway can be activated by interleukin-10 in Epstein-Barr virus infected B-cells. This may lead to the phosphorylation of c-Myc and thus the promotion of the cell cycle and mitotic events in Epstein-Barr infected cells. A further understanding of the role of interleukin-10, the Ras/ERK pathway and c-Myc activation may lead to novel therapeutic interventions for Burkitt's lymphoma pathogenesis in Epstein-Barr virus infected B cells. This study was accomplished by treating Burkitt's lymphoma cells, Epstein-Barr virus infected non-Burkitt's lymphoma cells, and non-infected, non-Burkitt's lymphoma cells with interleukin-10 and assessing the effects of interleukin-10 on the Ras/ERK pathway, c-Myc activation and Cyclin D1 production. Phosphorylation of ERK, total c-Myc and Cylclin D1 levels were significantly increased (p<0.05) in Epstein-Barr virus infected cells, where as IL-10 treatment decreased the viability of B cells lacking an Epstein-Barr infection. Ultimately leading to the conclusion, that IL-10 increases proliferation of Epstein-Barr virus infected B-lymphocytes

Epstein-Barr Virus Encephalitis: A Case Report

How to Cite This Article: Hashemian S, Ashrafzadeh F, Akhondian J, Beiraghi Toosi M. Epstein-Barr Virus Encephalitis: A Case Report. Iran J Child Neurol. 2015 Winter;9(1):107-110.  Abstract Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. EBV encephalitis is rare and is indicated as a wide range of clinical manifestations. We report a 10-year-old girl presented with fever, gait disturbance, and bizarre behavior for one week. The results of the physical examination were unremarkable. The diagnosis of EBV encephalitis was made by changes in titers of EBV specific antibodies and MRI findings. A cranial MRI demonstrated abnormal high signal intensities in the basal ganglia and the striatal body, especially in the putamen and caudate nucleus. EBV infection should be considered when lesions are localized to the basal ganglia.ReferencesFujimoto H, Asaoka K, Imiazumi T, Ayabe M, Shoji H, Kaji M. Epstein-Barr virus Infections of the Central Nervous System. Intern Med 2003; 42:33-40.Mathew AG, Parvez Y. Fulminant Epstein Barr virus encephalitis. Indian Pediatrics 2013; 50:418-419Kalita J, Maurya PK, Kumar B, Misra UK. Epstein Barr virus encephalitis: Clinical diversity and radiological similarity. Neurol India 2011; 59:605-7Baskin HJ, Hedlund G. Neuroimaging of Herpes Virus Infections in Children. Pediatr Radiol 2007; 37:949-63.Weinberg A, Li SH, Palmer M, Tyler K .Quantitative CSF PCR in Epstein-Barr Virus Infections of the Central Nervous System. Ann Neurol 2002; 52:543-8.Ono J, Shimizu K, Harada k, Mano T, Okada S. Characteristic MR Features of Encephalitis Caused by Epstein-Barr virus. Pediatr Radiol 1998; 28:569-70.Hausler M, Raamaekers T, Doenges M, Shweizer K ,Ritter K. Neurological Complications of Acute and Persistent Epstein-Barr Virus Infection in Pediatric Patients. Journal of Medical Virology 2002; 68:253-63.Young JY, Hyang LK. Transient Asymptomatic White Matter Lesions Following Epstein-Barr virus Encephalitis. Korean pediatric society 2011; 54:389- 93.Doja A, Bitnun A, Jones EL, Richardson S, Tellier R, Petric M, et al. Pediatric Epstein-Barr Virus-Associated Encephalitis:10-Year Review. Child Neurol 2006; 21:385-91.Kou K, Itoh M, Kawano Y. A Case Report of EB Virus- Induced Meningoencephalitis Associated with Brain MRI Abnormalities (basal ganglia). J Japan Peditr Sos 1994; 98:2052-9.Kunlong H, Hung-Tsai L, Minlan T. Epstein-Barr Virus Encephalitis in Children. Acta Pediatrica Taiwanica 2000; 3:140-6

Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.

Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted

EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS – TWO HERPES VIRUSES WITH ORAL MANIFESTATIONS.

Diseases caused by cytomegalovirus and Epstein-Barr virus are reported with increasing frequency. Epstein-Barr virus damages usually are due to reactivation of latent infection. while cytomegalovirus disease result from primary or reactivated infection in susceptible hosts. The booth infections can have oral manifestations

On the crossroad between tolerance and posttransplant lymphoma.

The role of the Epstein-Barr virus in the development of post-transplant lymphomas is well established. However, not all lymphomas that arise in these patients contain Epstein-Barr virus, suggesting that other cofactors are involved in tumor pathogenesis. We propose that immunologic interactions that result from the introduction of immunocompetent donor cells during transplantation contribute to a lymphomagenic environment in the host. Murine models of lymphoma that arises following transfer of allogeneic hematopoietic cells are discussed and are related to the transplant setting. One contemporary viewpoint of transplantation immunology holds that interactions between the host and donor components of the immune system determine the ultimate degree of tolerance or reciprocal immunoreactivity (eg, rejection, graft-versus-host disease) within the transplant patient. We conclude that host-donor immunologic microchimerism may also be an over-looked factor in the development of posttransplant lymphomas