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  1. Epstein-Barr virus test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003513.htm Epstein-Barr virus antibody test To use the sharing features on this page, please enable JavaScript. Epstein-Barr virus antibody test is a blood test to detect ...

  2. About Epstein-Barr Virus (EBV)

    Science.gov (United States)

    ... For Healthcare Providers Laboratory Testing References & Resources About Epstein-Barr Virus (EBV) Language: English (US) Español (Spanish) Recommend on ... On This Page Symptoms Transmission Diagnosis Prevention & Treatment Epstein-Barr virus (EBV), also known as human herpesvirus 4, is ...

  3. Epstein-Barr virus and the nervous system

    NARCIS (Netherlands)

    Portegies, P.; Corssmit, N.

    2000-01-01

    The neurological complications of Epstein-Barr virus infection include viral meningitis, encephalitis and neuromuscular complications. The introduction of cerebrospinal fluid polymerase chain reaction for Epstein-Barr virus DNA has improved diagnosis of these conditions and of primary central

  4. et d'Epstein-Barr virus (EBV)

    African Journals Online (AJOL)

    Diagnostic moléculaire du Cytomégalovirus (CMV), de l'herpès virus humain de type 6 (HHV6) et d'Epstein-Barr virus (EBV) par PCR en temps réel chez les femmes enceintes VIH séropositives et séronégatives à Ouagadougou, Burkina Faso.

  5. Epstein-Barr virus-induced systemic lupus erythematosus

    African Journals Online (AJOL)

    Ngou J. Graafland H, Segondy M. Antibodies against polypeptides of purified. Epstein-Barr virus in sera grown from patients with connective tissue diseases'. J Autoimmun 1992; 5: 243-249. 4. Stancek D, Rovensky J. Enhancement of Epstein-Barr virus antibody production in systemic lupus erythematosus patients.

  6. Epstein-Barr virus-associated lymphomas.

    Science.gov (United States)

    Shannon-Lowe, Claire; Rickinson, Alan B; Bell, Andrew I

    2017-10-19

    Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  7. Epstein-Barr virus and renal transplantation.

    Science.gov (United States)

    Le, Jade; Durand, Christine M; Agha, Irfan; Brennan, Daniel C

    2017-01-01

    Epstein-Barr virus (EBV) is a gamma herpesvirus associated with diseases ranging from asymptomatic viremia to post-transplant malignancies in kidney transplant recipients. EBV specifically is associated with post-transplantation lymphoproliferative disorder (PTLD), in kidney transplant recipients, with increased risk in EBV seronegative patients with EBV seropositive donors on intensified immunosuppression. The diagnosis of PTLD relies on clinical suspicion plus tissue biopsy with polymerase chain reaction (PCR) testing of blood currently used for risk determination in high-risk recipients. Therapeutic strategies for PTLD include reduction of immunosuppression, chemotherapy and rituximab, and consideration of sirolimus-based immunosuppression. Antivirals such as ganciclovir are used to prevent reactivation of cytomegalovirus and other herpes viruses but are not onco-therapeutic. Radiation therapy or surgery is indicated for bulky, disseminated or recalcitrant disease. Prognosis varies depending on the type of malignancy identified and stage of disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Tight regulation of the Epstein-Barr virus setpoint: interindividual differences in Epstein-Barr virus DNA load are conserved after HIV infection

    NARCIS (Netherlands)

    Piriou, Erwan; van Dort, Karel; Otto, Sigrid; van Oers, Marinus H. J.; van Baarle, Debbie

    2008-01-01

    Healthy individuals carry a constant number of Epstein-Barr virus-infected B cells in the peripheral blood over time. Here, we show that interindividual differences in Epstein-Barr virus DNA levels are maintained after HIV infection, providing evidence for the existence of an individual Epstein-Barr

  9. 21 CFR 866.3235 - Epstein-Barr virus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Epstein-Barr virus serological reagents. 866.3235... virus serological reagents. (a) Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in...

  10. The conundrum of the Epstein-Barr virus-associated gastric carcinoma in the Americas

    OpenAIRE

    Carrasco-Avino, Gonzalo; Riquelme, Ismael; Padilla, Oslando; Villaseca, Miguel; Aguayo, Francisco R.; Corvalan, Alejandro H.

    2017-01-01

    Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, B...

  11. Macular Amyloidosis and Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Yalda Nahidi

    2016-01-01

    Full Text Available Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group. There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8% and control (23.8% groups (P=0.08. Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis.

  12. Epstein-Barr Virus in Gastric Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Jun, E-mail: junnis@yamaguchi-u.ac.jp [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi [Department of Microbiology, Shimane University Faculty of Medicine, 89-1 Enyacho, Izumo City, Shimane 693-8501 (Japan); Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro [Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Oga, Atsunori [Department of Pathology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Yanai, Hideo [Department of Clinical Research, National Hospital Organization Kanmon Medical Center, 1-1 Sotoura, Chofu, Shimonoseki, Yamaguchi 752-8510 (Japan); Sakaida, Isao [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan)

    2014-11-07

    The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation.

  13. Molecular diagnostic of cytomegalovirus, Epstein Barr virus and ...

    African Journals Online (AJOL)

    Introduction: in most developing countries, Cytomegalovirus (CMV), Epstein Barr virus (EBV) and Herpes virus 6 (HHV-6) are not diagnosed in blood donors. The aim of this study is to determine the prevalence of these viruses in blood donors from the city of Ouagadougou, Burkina Faso. Methods: the study included 198 ...

  14. Epstein-Barr Virus: Clinical Diagnostics.

    Science.gov (United States)

    Niller, Hans-Helmut; Bauer, Georg

    2017-01-01

    The vast majority of the human adult population is infected with Epstein-Barr virus (EBV), and the majority of the EBV-infected individuals tolerates the infection well, without any further symptoms after primary infection. In cases of individuals which undergo primary infection in the form of an infectious mononucleosis, or which have undergone primary infection in their past, it is sometimes important to appraise symptomatic disease or differentiate infectious mononucleosis from other conditions. In these cases, serological methods, i.e., immunofluorescence, ELISA, or Western blot, are the methods of choice to come to an unequivocal diagnostic conclusion, while the detection and quantification of viral DNA through PCR plays a minor role.On the other hand, in a minority of the human population, EBV infection is associated or causally linked with autoimmune or malignant disease. Especially in the bone marrow or solid organ transplanted, or in otherwise severely immune-suppressed patients, prolonged EBV primary infection or EBV reactivation from latency may be a serious and life-threatening complication which needs to be diagnosed the faster the better, in order to take therapeutic steps in time. Determining the serostatus correctly is also important in these cases. However, the direct and quantitative detection of viral DNA are of importance for the diagnosis of serious EBV disease and its monitoring.In the following, we give an overview of diagnostic methods to accurately determine EBV serostatus and viral load. We evaluate the advantages and disadvantages of each method and report on the diagnostic significance of each and how to resolve diagnostic problems in case of uncertainties. For practical procedures, we refer to the detailed instruction manuals of the respective test kit manufacturers which have to be closely followed for reliable results.

  15. Mechanisms of immune evasion in Epstein-Barr virus infection

    NARCIS (Netherlands)

    Gram., A.M.

    2016-01-01

    The human herpesvirus Epstein-Barr virus (EBV) is a large DNA virus that infects over 90% of the adult world population. EBV is the causative agent of infectious mononucleosis and EBV infection is associated with various malignancies. EBV establishes lifelong infections in immunocompetent hosts. To

  16. Isotypes of Epstein-Barr virus antibodies in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Westergaard, Marie Wulff; Draborg, Anette Holck; Troelsen, Lone

    2015-01-01

    In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls...

  17. Lytic Replication of Epstein-Barr Virus During Space Flight

    Science.gov (United States)

    Stowe, R. P.; Pierson, D. L.; Barrett, A. D. T.

    1999-01-01

    Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Cellular immunity, which is decreased during and after space flight, is responsible for controlling EBV replication in vivo. In this study, we investigated the effects of short-term space flight on latent EBV reactivation.

  18. Recognition of Epstein-Barr Virus in Multiple Sclerosis

    NARCIS (Netherlands)

    G.P. van Nierop (Gijs)

    2018-01-01

    textabstractMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Symptoms of MS include cognitive, motoric, sensory and visual impairment, pain and fatigue. The genetic background of the host and infection with the herpesvirus family member Epstein-Barr virus

  19. Mechanisms of immune evasion in Epstein-Barr virus infection

    OpenAIRE

    Gram., A.M.

    2016-01-01

    The human herpesvirus Epstein-Barr virus (EBV) is a large DNA virus that infects over 90% of the adult world population. EBV is the causative agent of infectious mononucleosis and EBV infection is associated with various malignancies. EBV establishes lifelong infections in immunocompetent hosts. To counteract the host’s immune defence, EBV acquired numerous immune evasion mechanisms. During latency of EBV, viral protein synthesis is limited or absent, making the virus-infected cells virtually...

  20. Multiple Epstein-Barr virus infections in healthy individuals

    Science.gov (United States)

    Walling, Dennis M.; Brown, Abigail L.; Etienne, Wiguins; Keitel, Wendy A.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2003-01-01

    We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

  1. Epstein-Barr Virus Encephalitis in an Immunocompetent Child: A Case Report and Management of Epstein-Barr Virus Encephalitis

    Directory of Open Access Journals (Sweden)

    Gulsen Akkoc

    2016-01-01

    Full Text Available Epstein-Barr virus (EBV usually causes mild, asymptomatic, and self-limited infections in children and adults; however, it may occasionally lead to severe conditions such as neurological diseases, malignant diseases, hepatic failure, and myocarditis. Epstein-Barr virus-related neurological disorders include meningitis, encephalitis, and cranial or peripheral neuritis, which are mostly seen in immunocompromised patients. The therapeutic modalities for EBV-related severe organ damage including central nervous system manifestations are still uncertain. Herein, we describe a seven-year-old boy with EBV encephalitis who presented with prolonged fever, exudative pharyngitis, reduced consciousness, and neck stiffness. Cranial magnetic resonance imaging showed contrast enhancement in the bilateral insular cortex and the right hypothalamus. The diagnosis was made by EBV-DNA amplification in both the blood and cerebrospinal fluid samples. He was discharged with acyclovir therapy without any sequelae.

  2. Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

    Science.gov (United States)

    Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

    2017-10-01

    Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

  3. Quantification of Epstein-Barr virus-DNA load in lung transplant recipients : A comparison of plasma versus whole blood

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; Verschuuren, Erik A.; Veeger, Nic J.; van der Bij, Wim; van Imhoff, Gustaaf W.; Kallenberg, Cees G.; Hepkema, Bouke G.

    2008-01-01

    Background: Monitoring of the Epstein-Barr virus-DNA load is frequently used to identify patients at risk for post-transplant lymphoproliferative disease (PTLD). Epstein-Barr virus DNA can be measured in the plasma and whole blood serum compartments. Methods: We compared levels of Epstein-Barr virus

  4. The conundrum of the Epstein-Barr virus-associated gastric carcinoma in the Americas.

    Science.gov (United States)

    Carrasco-Avino, Gonzalo; Riquelme, Ismael; Padilla, Oslando; Villaseca, Miguel; Aguayo, Francisco R; Corvalan, Alejandro H

    2017-09-26

    Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, BARTs and LMP are the highest expressed genes; their variations in healthy individuals may explain the phylogeographic diversity of Epstein-Barr virus across the region. Gastric cancer cases harbor exclusively the western genotype (subtype D and kept Xho I site), suggesting a disrupted co-evolution between the pathogen and its host. Epstein-Barr virus-associated gastric carcinoma molecular subtype cases from The Cancer Genome Atlas display PIK3CA gene mutations, amplification of JAK2, PD-L1 and PD-L2 and CpG island methylator phenotype, leading to more extensive methylation of host and viral genomes than any other subtypes from the study. Environmental conditions include negative- and positive- associations with being firstborn child and smoking, respectively. A marginal association with H. pylori has also been reported. Lymphoepithelioma-like carcinoma is associated with Epstein Barr virus in 80%-86% of cases, most of which have been included as part of Epstein Barr virus-associated gastric carcinoma series (prevalence 1.1%-7.6%). Whether these cases represent a variant of Epstein-Barr virus-associated gastric carcinoma is discussed. We propose novel research strategies to solve the conundrum of the high prevalence of Epstein-Barr virus-associated gastric carcinoma in the Americas.

  5. Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

    Science.gov (United States)

    Nandakumar, Athira; Uwatoko, Futoshi; Yamamoto, Megumi; Tomita, Kazuo; Majima, Hideyuki J; Akiba, Suminori; Koriyama, Chihaya

    2017-07-01

    Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

  6. Frequency of epstein-barr virus in classical hodgkin Lymphoma.

    Science.gov (United States)

    Azhar, Muhammad; Din, Hafeez Ud; Muhammad, Iqbal; Hashmi, Shoaib Naiyar; Akhtar, Farhan

    2016-01-01

    Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Out of 55 patients, 38 (69%) were male and 17 (31%) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80%) were positive for latent membrane protein-1. Among positive cases 32 (72.72%) were male and 12 (27.28%) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3% as well as among both genders. Out of total 55 cases, 79.16% (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33% (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100% (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80% of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16% cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100% of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma and lymphocyte rich classical Hodgkin lymphoma.

  7. Comprehensive profiling of functional Epstein-Barr virus miRNA expression in human cell lines

    NARCIS (Netherlands)

    Hooykaas, Marjolein J G; Kruse, Elisabeth; Wiertz, Emmanuel J H J; Lebbink, Robert Jan

    2016-01-01

    BACKGROUND: Epstein-Barr virus (EBV) establishes lifelong infections in its human host. The virus is associated with a broad range of malignancies of lymphoid and epithelial origin, including Burkitt's lymphoma, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma and gastric

  8. Immune Evasion by Epstein-Barr Virus

    NARCIS (Netherlands)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, EJHJ

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to

  9. Recent advances in understanding Epstein-Barr virus

    Science.gov (United States)

    Stanfield, Brent A.; Luftig, Micah A.

    2017-01-01

    Epstein-Barr virus (EBV) is a common human herpes virus known to infect the majority of the world population. Infection with EBV is often asymptomatic but can manifest in a range of pathologies from infectious mononucleosis to severe cancers of epithelial and lymphocytic origin. Indeed, in the past decade, EBV has been linked to nearly 10% of all gastric cancers. Furthermore, recent advances in high-throughput next-generation sequencing and the development of humanized mice, which effectively model EBV pathogenesis, have led to a wealth of knowledge pertaining to strain variation and host-pathogen interaction. This review highlights some recent advances in our understanding of EBV biology, focusing on new findings on the early events of infection, the role EBV plays in gastric cancer, new strain variation, and humanized mouse models of EBV infection. PMID:28408983

  10. Valganciclovir for the Suppression of Epstein-Barr Virus Replication.

    Science.gov (United States)

    Yager, Jessica E; Magaret, Amalia S; Kuntz, Steven R; Selke, Stacy; Huang, Meei-Li; Corey, Lawrence; Casper, Corey; Wald, Anna

    2017-07-15

    Epstein-Barr virus (EBV) causes infectious mononucleosis and can lead to lymphoproliferative diseases. We evaluated the effects of valganciclovir on oral EBV shedding in a randomized, double-blind, placebo-controlled study. Twenty-six men received oral valganciclovir or daily placebo for 8 weeks, followed by a 2-week "washout period" and then 8 weeks of the alternative treatment. Valganciclovir reduced the proportion of days with EBV detected from 61.3% to 17.8% (relative risk, 0.28; 95% confidence interval [CI], .21-.41; P virus detected by 0.77 logs (95% CI, .62-.91 logs; P < .001). Further investigations into the impact of valganciclovir on EBV-associated diseases are needed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  11. Mannose-binding lectin genotypes and susceptibility to epstein-barr virus infection in infancy

    DEFF Research Database (Denmark)

    Friborg, Jeppe T; Jarrett, Ruth F; Koch, Anders

    2010-01-01

    In a cohort study of children Epstein-Barr virus (EBV) antibody levels were determined. EBV seropositivity was significantly lower and time to seroconversion increased in MBL-insufficient compared with MBL-sufficient children...

  12. Clinical Trials Using Adenovirus/Cytomegalovirus/Epstein-Barr Virus-specific Allogeneic Cytotoxic T Lymphocytes

    Science.gov (United States)

    NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovirus/cytomegalovirus/epstein-barr virus-specific allogeneic cytotoxic t lymphocytes.

  13. Immune Evasion by Epstein-Barr Virus.

    Science.gov (United States)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, Emmanuel J H J

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.

  14. Epstein-Barr Virus in Classical Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Azhar, M.; Din, H. U.; Muhammad, I.; Hashmi, S. N.; Akhtar, F.

    2016-01-01

    Background: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. Method: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Results: Out of 55 patients, 38 (69 percent) were male and 17 (31 percent) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80 percent) were positive for latent membrane protein-1. Among positive cases 32 (72.72 percent) were male and 12 (27.28 percent) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3 percent as well as among both genders. Out of total 55 cases, 79.16 percent (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33 percent (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100 percent (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80 percent of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16 percent cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100 percent of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. Conclusion: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma

  15. Phosphorylation of the Epstein-Barr virus nuclear antigen 2

    DEFF Research Database (Denmark)

    Grässer, F A; Göttel, S; Haiss, P

    1992-01-01

    A major in vivo phosphorylation site of the Epstein-Barr virus nuclear antigen 2 (EBNA-2) was found to be localized at the C-terminus of the protein. In vitro phosphorylation studies using casein kinase 1 (CK-1) and casein kinase 2 (CK-2) revealed that EBNA-2 is a substrate for CK-2, but not for CK......-1. The CK-2 specific phosphorylation site was localized in the 140 C-terminal amino acids using a recombinant trpE-C-terminal fusion protein. In a similar experiment, the 58 N-terminal amino acids expressed as a recombinant trpE-fusion protein were not phosphorylated. Phosphorylation of a synthetic...

  16. Epstein-Barr virus encephalitis and encephalomyelitis: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Shian, W.J. [Department of Pediatrics, Tao-Yuan Veterans Hospital, No. 100, Sec 3, Cheng-Kung Rd, City of Tao-Yuan, Taiwan (Taiwan, Province of China); Chi, C.S. [Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan (Taiwan, Province of China)

    1996-09-01

    The purpose of this project is to investigate the clinical and brain MR characteristics of Epstein-Barr virus (EBV) encephalitis and encephalomyelitis. Clinical and 30 MR findings of 29 patients with EBV encephalitis or encephalomyelitis were retrospectively reviewed. Patients included 24 with encephalitis, 3 with encephalomyelitis, and 2 with brain-stem encephalitis. Altered consciousness, seizures, visual hallucination, and acute psychotic reaction were the common presentations. Eight patients had positive MR findings. These included T2 prolongation over gray and white matter, periventricular leukomalacia, and brain atrophy. Transient T2 prolongation over gray and white matter was found in one patient. Our results indicate that EBV encephalitis and encephalomyelitis have a wide range of both clinical and MR findings. The MR lesions may disappear in a short period, so the timing for the MR scan may be critical. (orig.). With 5 figs., 2 tabs.

  17. Epstein-Barr virus: a master epigenetic manipulator.

    Science.gov (United States)

    Scott, Rona S

    2017-10-01

    Like all herpesviruses, the ability of Epstein-Barr virus (EBV) to establish life-long persistent infections is related to a biphasic viral lifecycle that involves latency and reactivation/lytic replication. Memory B cells serve as the EBV latency compartment where silencing of viral gene expression allows maintenance of the viral genome, avoidance of immune surveillance, and life-long carriage. Upon viral reactivation, viral gene expression is induced for replication, progeny virion production, and viral spread. EBV uses the host epigenetic machinery to regulate its distinct viral gene expression states. However, epigenetic manipulation by EBV affects the host epigenome by reprogramming cells in ways that leave long-lasting, oncogenic phenotypes. Such virally-induced epigenetic alterations are evident in EBV-associated cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Epstein-Barr virus infection and nasopharyngeal carcinoma.

    Science.gov (United States)

    Tsao, Sai Wah; Tsang, Chi Man; Lo, Kwok Wai

    2017-10-19

    Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  19. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    Science.gov (United States)

    ... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  20. Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

    NARCIS (Netherlands)

    Sonke, Gabe S.; Ludwig, Inge; van Oosten, Hannah; Baars, Joke W.; Meijer, Ellen; Kater, Arnon P.; de Jong, Daphne

    2008-01-01

    Chronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis. These 2 abnormal

  1. Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

    NARCIS (Netherlands)

    G.S. Sonke (Gabe); I. Ludwig (Inge); H. van Oosten (Hannah); J.W. Baars (Joke); E. Meijer (Ellen); A.P. Kater (Arnon); D. de Jong (Daphne)

    2008-01-01

    textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2

  2. Epstein-Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A antibodies in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Draborg, A H; Jørgensen, J M; Müller, H

    2012-01-01

    We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients.......We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients....

  3. Epstein-Barr virus association with peptic ulcer disease.

    Science.gov (United States)

    Cárdenas-Mondragón, María G; Torres, Javier; Flores-Luna, Lourdes; Carreón-Talavera, Ricardo; Camorlinga-Ponce, Margarita; Fuentes-Pananá, Ezequiel M

    2015-01-01

    Background. Helicobacter pylori (HP) infection and nonsteroidal anti-inflammatory drugs (NSAID) use are considered the main risk to develop peptic ulcer disease (PUD). However, PUD also occurs in the absence of HP infection and/or NSAID use. Recently, we have found evidence that Epstein-Barr virus (EBV) reactivation increases the risk to develop premalignant and malignant gastric lesions. Objective. To study a possible association between EBV and PUD. Methods. Antibodies against an EBV reactivation antigen, HP, and the HP virulence factor CagA were measured in sera from 207 Mexican subjects, controls (healthy individuals, n = 129), and PUD patients (n = 78, 58 duodenal and 20 gastric ulcers). Statistical associations were estimated. Results. Duodenal PUD was significantly associated with high anti-EBV IgG titers (p = 0.022, OR = 2.5), while anti-EBV IgA was positively associated with gastric PUD (p = 0.002, OR = 10.1). Conclusions. Our study suggests that EBV reactivation in gastric and duodenal epithelium increases the risk to develop PUD.

  4. How we treat chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Sawada, Akihisa; Inoue, Masami; Kawa, Keisei

    2017-04-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of the EBV-associated T- or NK-cell lymphoproliferative diseases, which also include hypersensitivity to mosquito bites and severe-type hydroavacciniforme. The manifestations of CAEBV are often self-limiting with minimum supportive care or only prednisolone and cyclosporine A with or without etoposide. However, allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure, without which patients with CAEBV die within several years. A severe hypercytokinemia and hemophagocytic syndrome, which may occur suddenly, often results in a fatal clinical course. At out institute, we have established a 3-step strategy, including allogeneic HSCT, for the treatment of CAEBV. Seventy-nine patients with CAEBV and related diseases have been treated to date. The 3-year overall survival rate (3y-OS) is currently 87.3 ± 4.2% after planned allogeneic HSCT. However, 3y-OS in patients with uncontrolled active disease is only 16.7 ± 10.8%. To maximize survival rates with minimized late sequelae, we recommend earlier initiation and completion of the 3-step treatment without watchful waiting. We present six illustrative and difficult cases (including severe hypercytokinemia or emergent HSCT) and discuss them together with 73 residual cases.

  5. Epstein-Barr Virus Association with Peptic Ulcer Disease

    Directory of Open Access Journals (Sweden)

    María G. Cárdenas-Mondragón

    2015-01-01

    Full Text Available Background. Helicobacter pylori (HP infection and nonsteroidal anti-inflammatory drugs (NSAID use are considered the main risk to develop peptic ulcer disease (PUD. However, PUD also occurs in the absence of HP infection and/or NSAID use. Recently, we have found evidence that Epstein-Barr virus (EBV reactivation increases the risk to develop premalignant and malignant gastric lesions. Objective. To study a possible association between EBV and PUD. Methods. Antibodies against an EBV reactivation antigen, HP, and the HP virulence factor CagA were measured in sera from 207 Mexican subjects, controls (healthy individuals, n = 129, and PUD patients (n = 78, 58 duodenal and 20 gastric ulcers. Statistical associations were estimated. Results. Duodenal PUD was significantly associated with high anti-EBV IgG titers (p = 0.022, OR = 2.5, while anti-EBV IgA was positively associated with gastric PUD (p = 0.002, OR = 10.1. Conclusions. Our study suggests that EBV reactivation in gastric and duodenal epithelium increases the risk to develop PUD.

  6. Epstein-Barr Virus (EBV)-associated Gastric Carcinoma

    Science.gov (United States)

    Iizasa, Hisashi; Nanbo, Asuka; Nishikawa, Jun; Jinushi, Masahisa; Yoshiyama, Hironori

    2012-01-01

    The ubiquitous Epstein-Barr virus (EBV) is associated with several human tumors, which include lymphoid and epithelial malignancies. It is known that EBV persistently infects the memory B cell pool of healthy individuals by activating growth and survival signaling pathways that can contribute to B cell lymphomagenesis. Although the monoclonal proliferation of EBV-infected cells can be observed in epithelial tumors, such as nasopharyngeal carcinoma and EBV-associated gastric carcinoma, the precise role of EBV in the carcinogenic progress is not fully understood. This review features characteristics and current understanding of EBV-associated gastric carcinoma. EBV-associated gastric carcinoma comprises almost 10% of all gastric carcinoma cases and expresses restricted EBV latent genes (Latency I). Firstly, definition, epidemiology, and clinical features are discussed. Then, the route of infection and carcinogenic role of viral genes are presented. Of particular interest, the association with frequent genomic CpG methylation and role of miRNA for carcinogenesis are topically discussed. Finally, the possibility of therapies targeting EBV-associated gastric carcinoma is proposed. PMID:23342366

  7. Epstein-Barr virus encephalitis in solid organ transplantation.

    Science.gov (United States)

    Lau, Jillian S Y; Low, Zhi Mei; Abbott, Iain; Shochet, Lani; Kanellis, John; Kitching, Arthur Richard; Korman, Tony M

    2017-07-01

    Epstein-Barr virus (EBV) is typically associated with post transplant lymphoproliferative disease (PTLD) after solid organ and stem cell transplantation. However, it is rarely associated with neurological complications. We report a case of severe encephalitis complicating primary EBV infection six months post renal transplantation, and review the literature on EBV encephalitis in solid organ transplantation in adults. A 55-year-old male presented 6 months post cadaveric renal transplant with headache, fever and confusion. Neuroimaging was unremarkable, but an electroencephalogram was consistent with diffuse encephalopathy. EBV DNA was detected in both cerebrospinal fluid (13,177 copies/ml), and plasma (14,166 copies/ml). Management included reduction of immunosuppression, intravenous ganciclovir and intravenous immunoglobulin, and resulted in a reduction in EBV viral load in both plasma and cerebrospinal fluid. The patient made a full recovery with no long-term neurological deficits and preservation of the graft. This case highlights the importance of knowing donor and recipient EBV serostatus at time of transplant, and closely monitoring EBV DNA when there is a mismatch. Ganciclovir or valganciclovir prophylaxis has also been shown to reduce the incidence of primary EBV infection in renal transplantation in these recipients. Treatment options for EBV infection post-transplant include reduction of immunosuppression, antiviral therapy, IVIg, and monoclonal antibody therapy directed toward infected B lymphocytes.

  8. Epstein-Barr Virus in Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Anette Holck Draborg

    2013-01-01

    Full Text Available Systemic autoimmune diseases (SADs are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, and Sjögren’s syndrome (SS and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

  9. Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

    Science.gov (United States)

    Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

    2016-07-01

    The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Prevalence of herpes simplex, Epstein Barr and human papilloma viruses in oral lichen planus.

    Science.gov (United States)

    Yildirim, Benay; Sengüven, Burcu; Demir, Cem

    2011-03-01

    The aim of the present study was to assess the prevalence of Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus -16 in oral lichen planus cases and to evaluate whether any clinical variant, histopathological or demographic feature correlates with these viruses. The study was conducted on 65 cases. Viruses were detected immunohistochemically. We evaluated the histopathological and demographic features and statistically analysed correlation of these features with Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus-16 positivity. Herpes Simplex virus was positive in six (9%) cases and this was not statistically significant. The number of Epstein Barr virus positive cases was 23 (35%) and it was statistically significant. Human Papilloma virus positivity in 14 cases (21%) was statistically significant. Except basal cell degeneration in Herpes Simplex virus positive cases, we did not observe any significant correlation between virus positivity and demographic or histopathological features. However an increased risk of Epstein Barr virus and Human Papilloma virus infection was noted in oral lichen planus cases. Taking into account the oncogenic potential of both viruses, oral lichen planus cases should be detected for the presence of these viruses.

  11. Complex forms of mitochondrial DNA in human B cells transformed by Epstein-Barr virus (EBV)

    DEFF Research Database (Denmark)

    Christiansen, Gunna; Christiansen, C; Zeuthen, J

    1983-01-01

    Human lymphocytes and lymphoid cell lines were analyzed for the presence of complex forms of mitochondrial DNA (mtDNA) by electron microscopy. A high frequency (9%-14.5%) of catenated dimers, circular dimers, or oligomers were found in samples from Epstein-Barr-virus-(EBV) transformed lymphoblast......Human lymphocytes and lymphoid cell lines were analyzed for the presence of complex forms of mitochondrial DNA (mtDNA) by electron microscopy. A high frequency (9%-14.5%) of catenated dimers, circular dimers, or oligomers were found in samples from Epstein-Barr-virus-(EBV) transformed...

  12. Epstein-Barr Virus Infection in Children: Improving the Diagnosis and Treatment Program

    Directory of Open Access Journals (Sweden)

    E. N. Simovanyan

    2016-01-01

    Full Text Available Widespread, severe course, frequent development of chronic forms, adverse effects of the Epstein-Barr virus infection to the health of children, the difficulties of diagnosis and therapy dictate the need to improve the diagnostic and treatment programs in this disease. A total of 286 patients with acute and chronic Epstein-Barr virus infection. It was established, that for the timely diagnosis of the disease requires a comprehensive analysis of anamnesis, clinical symptoms, including symptoms of acute and chronic mononucleosis syndrome in combination with multiorgan pathology, and the results of laboratory examination (enzyme immunoassay, polymerase chain reaction, immune status.

  13. Epstein-Barr virus infection in chronically inflamed periapical granulomas.

    Directory of Open Access Journals (Sweden)

    Kosuke Makino

    Full Text Available Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV using surgically removed periapical granulomas (n = 32. EBV DNA was detected in 25 of 32 periapical granulomas (78.1% by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10; the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001. Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1 of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas.

  14. Epstein-Barr virus shedding by astronauts during space flight

    Science.gov (United States)

    Pierson, D. L.; Stowe, R. P.; Phillips, T. M.; Lugg, D. J.; Mehta, S. K.

    2005-01-01

    Patterns of Epstein-Barr virus (EBV) reactivation in 32 astronauts and 18 healthy age-matched control subjects were characterized by quantifying EBV shedding. Saliva samples were collected from astronauts before, during, and after 10 space shuttle missions of 5-14 days duration. At one time point or another, EBV was detected in saliva from each of the astronauts. Of 1398 saliva specimens from 32 astronauts, polymerase chain reaction analysis showed that 314 (23%) were positive for EBV DNA. Examination by flight phase showed that 29% of the saliva specimens collected from 28 astronauts before flight were positive for EBV DNA, as were 16% of those collected from 25 astronauts during flight and 16% of those collected after flight from 23 astronauts. The mean number of EBV copies from samples taken during the flights was 417 per mL, significantly greater (p<.05) than the number of viral copies from the preflight (40) and postflight (44) phases. In contrast, the control subjects shed EBV DNA with a frequency of 3.7% and mean number of EBV copies of 40 per mL of saliva. Ten days before flight and on landing day, titers of antibody to EBV viral capsid antigen were significantly (p<.05) greater than baseline levels. On landing day, urinary levels of cortisol and catecholamines were greater than their preflight values. In a limited study (n=5), plasma levels of substance P and other neuropeptides were also greater on landing day. Increases in the number of viral copies and in the amount of EBV-specific antibody were consistent with EBV reactivation before, during, and after space flight.

  15. Mouse model for acute Epstein-Barr virus infection.

    Science.gov (United States)

    Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

    2016-11-29

    Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

  16. Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Hørding, U; Nielsen, H W

    1994-01-01

    sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace...

  17. Etiologic Association between Epstein-Barr Virus and Oral Squamous Cell Carcinoma: A Brief Evidence-based Discussion.

    Science.gov (United States)

    Majumdar, Barnali; Sarode, Sachin C; Sarode, Gargi S; Patil, Shankargouda

    2017-04-01

    Epstein-Barr virus (EBV), also known as human herpes virus-4, belongs to the γ-subfamily of herpes viruses. 1 Nearly 90 to 95% of the world's adult population is an asymptomatic carrier of EBV. 1-3 .

  18. Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge.

    Science.gov (United States)

    Bolis, Vasileios; Karadedos, Christos; Chiotis, Ioannis; Chaliasos, Nikolaos; Tsabouri, Sophia

    2016-01-01

    Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein-Barr virus infection. Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation." Epstein-Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein-Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein-Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Emotional Disclosure through Writing or Speaking Modulates Latent Epstein-Barr Virus Antibody Titers.

    Science.gov (United States)

    Esterling, Brian A.; And Others

    1994-01-01

    Healthy Epstein-Barr virus (EBV) seropositive undergraduates (n=57) completed personality inventory, provided blood samples, and were randomly assigned to write/talk about stressful events, or to write about trivial events. Those assigned to verbal/stressful condition had significantly lower EBV antibody titers (suggesting better cellular immune…

  20. Epidemiology of Classical Hodgkin Lymphoma and Its Association with Epstein Barr Virus in Northern China

    NARCIS (Netherlands)

    Huang, Xin; Nolte, Ilja; Gao, Zifen; Vos, Hans; Hepkema, Bouke; Poppema, Sibrand; van den Berg, Anke; Diepstra, Arjan

    2011-01-01

    Background: The incidence of classical Hodgkin lymphoma (cHL) and its association with Epstein-Barr virus (EBV) varies significantly with age, sex, ethnicity and geographic location. This is the first report on epidemiological features of cHL patients from Northern regions of China. These features

  1. Epstein-Barr-virus-associeret lymfom hos en patient med colitis ulcerosa i behandling med azathioprin

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Kiszka-Kanowitz, Marianne; Albrectsen, Jens Mørch

    2008-01-01

    A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV...

  2. Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Heiden, Julie

    2018-01-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed...

  3. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    DEFF Research Database (Denmark)

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired...

  4. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.

    LENUS (Irish Health Repository)

    Urayama, Kevin Y

    2012-02-08

    Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification.

  5. Epstein-Barr Virus: The Path from Latent to Productive Infection.

    Science.gov (United States)

    Chiu, Ya-Fang; Sugden, Bill

    2016-09-29

    The intrinsic properties of different viruses have driven their study. For example, the capacity for efficient productive infection of cultured cells by herpes simplex virus 1 has made it a paradigm for this mode of infection for herpesviruses in general. Epstein-Barr virus, another herpesvirus, has two properties that have driven its study: It causes human cancers, and it exhibits a tractable transition from its latent to its productive cycle in cell culture. Here, we review our understanding of the path Epstein-Barr virus follows to move from a latent infection to and through its productive cycle. We use information from human infections to provide a framework for describing studies in cell culture and, where possible, the molecular resolutions from these studies. We also pose questions whose answers we think are pivotal to understanding this path, and we provide answers where we can.

  6. Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding

    OpenAIRE

    Sanosyan, Armen; Rutagwera, David Gatsinzi; Moles, Jean-Pierre; Bollore, Karine; Peries, Marianne; Kankasa, Chipepo; Mwiya, Mwiya; Tylleskär, Thorkild; Nagot, Nicolas; Van de Perre, Philippe; Tuaillon, Edouard

    2016-01-01

    Abstract Epstein?Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case?control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers. The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples ...

  7. Mapping of polypeptides encoded by the Epstein-Barr virus genome in productive infection.

    OpenAIRE

    Hummel, M; Kieff, E

    1982-01-01

    Over 30 viral-specified polypeptides are translated in vitro from RNA of cells productively infected with Epstein-Barr virus (EBV). The polypeptides map to sites in EBV DNA by hybrid selection. Almost all of the polypeptides are reactive with EBV immune human serum. Several of the polypeptides are part of the early antigen complex. Two others are likely to be major structural components of the virus. Genes encoding persistent early and late polypeptides are intermixed through most of the EBV ...

  8. The Long and Complicated Relationship between Epstein-Barr Virus and Epithelial Cells.

    Science.gov (United States)

    Hutt-Fletcher, Lindsey M

    2017-01-01

    The roles of epithelial cells in infection and persistence of the Epstein-Barr virus (EBV) have long been difficult to resolve. However, recent developments have reinforced the conclusion that these cells are a major site of virus replication and raised the possibility that, like papillomaviruses, EBV has evolved to take advantage of epithelial differentiation to ensure survival, persistence, and spread. Copyright © 2016 American Society for Microbiology.

  9. Clinical significance of spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia in Epstein-Barr virus-associated and Epstein-Barr virus-negative gastric cancer.

    Science.gov (United States)

    Zhang, Yu; Chen, Jian-Ning; Dong, Min; Zhang, Zhi-Gang; Zhang, Yi-Wang; Wu, Jun-Yan; Du, Hong; Li, Hai-Gang; Huang, Yan; Shao, Chun-Kui

    2017-05-01

    Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM) have been recognized as neoplastic precursors in gastric carcinogenesis. We explored the relationship between SPEM and IM in Epstein-Barr virus-associated (EBVaGC) and Epstein-Barr virus-negative (EBVnGC) gastric cancer. Sixty-four EBVaGC and one hundred and fifty-four EBVnGC patients were included. EBV positivity was identified using Epstein-Barr virus-encoded RNA-1 in situ hybridization. SPEM was subclassified into absent, early, and advanced SPEM. Acute and chronic inflammation was graded as absent, mild, moderate, and marked. Univariate and multivariate logistic regression analyses were conducted to analyze the correlation between SPEM, IM, and inflammation. Our study revealed that SPEM was detected in 87.5% EBVaGC and 85.1% EBVnGC patients. Distribution of patients according to the SPEM classification was significantly different between EBVaGC and EBVnGC groups (P=.038). IM was observed less frequently in EBVaGC when compared with EBVnGC patients (P<.001). No difference was observed between EBVaGC and EBVnGC in the levels of acute and chronic inflammation. A positive correlation between IM and SPEM status was observed in both EBVaGC and EBVnGC patients. Furthermore, advanced SPEM was an independent influential factor to IM in EBVnGC (P=.013). In conclusion, SPEM was associated with both EBVaGC and EBVnGC more frequently than IM. Moreover, advanced SPEM had a stronger association with IM than early SPEM in EBVnGC. These results suggest that identification of SPEM should be used as a high-risk indicator for detecting early gastric carcinoma, and should be brought to the attention of pathologists and clinicians. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Filaggrin gene polymorphism associated with Epstein-Barr virus-associated tumors in China.

    Science.gov (United States)

    Yang, Yang; Liu, Wen; Zhao, Zhenzhen; Zhang, Yan; Xiao, Hua; Luo, Bing

    2017-08-01

    Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris, while recently FLG mutations were found to be associated with gastric cancer. This study aimed to investigate the association of filaggrin polymorphism with Epstein-Barr virus-associated tumors in China. A total of 200 patients with three types of tumors and 117 normal control samples were genotyped at three common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY technique. The χ 2 test was used to evaluate the relationship between the mutation and the three kinds of tumors. A two-sided P value of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were verified to be different in both SNP loci.

  11. Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, H.; Kusuhara, T.; Honda, Y.; Hino, H. (1. Dept. (Neurology) of Internal Medicine, Kurume Univ. School of Medicine (Japan)); Kojima, K.; Abe, T. (Dept. of Radiology, Kurume Univ. School of Medicine (Japan)); Watanabe, M. (Dept. of Neurosurgery, Koyanagi Hospital, Saga (Japan))

    1992-08-01

    A 25-year-old women had a fever, left cervical lymphadenopathy, neurological symptoms and signs, CSF pleocytosis and persistent high serum antibodies to the Epstein-Barr virus (EBV); she had a recurrence 1 year later. She was thought to have relapsing acute disseminated encephalomyelitis associated with chronic EBV infection. MRI revealed abnormalities, mainly in the right basal ganglia and left midbrain. At the time of the recurrence, further abnormalities appeared in the opposite basal ganglia and right cerebral white matter. (orig.).

  12. Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

    Science.gov (United States)

    Moretti, Milena; Lava, Sebastiano A G; Zgraggen, Lorenzo; Simonetti, Giacomo D; Kottanattu, Lisa; Bianchetti, Mario G; Milani, Gregorio P

    2017-06-01

    Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity. Stimulated by our experience with two cases, we performed a review of the literature. The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered. In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A distinct subtype of Epstein Barr virus positive T/NK-cell lymphoproliferative disorder: Adult patients with chronic active Epstein Barr virus infection-like features.

    Science.gov (United States)

    Kawamoto, Keisuke; Miyoshi, Hiroaki; Suzuki, Takaharu; Kozai, Yasuji; Kato, Koji; Miyahara, Masaharu; Yujiri, Toshiaki; Oishi, Naoki; Choi, Ilseung; Fujimaki, Katsumichi; Muta, Tsuyoshi; Kume, Masaaki; Moriguchi, Sayaka; Tamura, Shinobu; Kato, Takeharu; Tagawa, Hiroyuki; Makiyama, Junya; Kanisawa, Yuji; Sasaki, Yuya; Kurita, Daisuke; Yamada, Kyohei; Shimono, Joji; Sone, Hirohito; Takizawa, Jun; Seto, Masao; Kimura, Hiroshi; Ohshima, Koichi

    2017-12-14

    The characteristics of adult patients with chronic active Epstein-Barr virus infection (adult-onset CAEBV) are poorly recognized, hindering early diagnosis and an improved prognosis. Adult-onset CAEBV (n = 54) diagnosed between 2005 and 2015 were conducted. Adult-onset was defined as an estimated age of onset ≥15 years. To characterize the clinical features of adult-onset CAEBV, we compared them to those of pediatric-onset (estimated age of onset Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P = 0.0087, P = 0.0236, and P = 0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P = 0.0289). Compared to that for pediatric-onset CAEBV and ENKTL, adult-onset CAEBV had a poorer prognosis (P < 0.001 and P = 0.0484, respectively). CAEBV can develop in a wide age-range, with clinical differences between adult-onset and pediatric-onset CAEBV. Adult-onset CAEBV is a disease with a poor prognosis and further research is needed. Copyright © 2017, Ferrata Storti Foundation.

  14. Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

    DEFF Research Database (Denmark)

    Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J

    2016-01-01

    of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly...

  15. Immune responses to Epstein?Barr virus: molecular interactions in the virus evasion of CD8+ T cell immunity

    OpenAIRE

    Rowe, Martin; Zuo, Jianmin

    2010-01-01

    Persistent viruses have mechanisms for modulating the host immune responses that are essential for achieving a lifelong virus?host balance while minimizing the viral pathogenicity. Here we review some of the immune-modulating mechanisms evolved by the ubiquitous but potentially oncogenic Epstein?Barr virus, with particular emphasis on the molecular mechanisms of genes interfering with HLA class I antigen presentation.

  16. Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis.

    Science.gov (United States)

    Giudice, Aldo; D'Arena, Giovanni; Crispo, Anna; Tecce, Mario Felice; Nocerino, Flavia; Grimaldi, Maria; Rotondo, Emanuela; D'Ursi, Anna Maria; Scrima, Mario; Galdiero, Massimiliano; Ciliberto, Gennaro; Capunzo, Mario; Franci, Gianluigi; Barbieri, Antonio; Bimonte, Sabrina; Montella, Maurizio

    2016-01-01

    MicroRNAs are short (21-23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single-cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein-Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein-Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein-Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein-Barr virus-encoded viral proteins and related epigenetic alterations as well as the roles of Epstein-Barr virus-encoded and virally modulated cellular miRNAs.

  17. Soro-epidemiologia do virus de Epstein-Barr (VEB The seroepidemiology of the Epstein-Barr vírus (EBV

    Directory of Open Access Journals (Sweden)

    Claudio Sergio Pannuti

    1981-02-01

    Full Text Available É feita revisão dos estudos soro-epidemiológicos do vírus de Epstein-Barr (vírus EB, mostrando a ubicuidade deste vírus, bem como sua relação com doenças malígnas e não malígnas do homem. O desenvolvimento de novas técnicas laboratoriais e o acúmulo, nos últimos 10 anos, de grande número de estudos soro-epidemiológicos, levaram à conclusão de que, além da associação etiológica com a mononucleose infecciosa, torna-se cada vez mais evidente a ligação do vírus EB com o linfoma de Burkitt e com o carcinoma do nasofaringe. Estas observações, além de sua extraordinária importância intrínseca, tem sido de grande utilidade para a melhor compreensão dos possíveis mecanismos e efeitos das infecções virais no homem.Since the discovery of the Epstein-Barr virus (EBV in 1964, seroepidemiological studies have sought to characterize this member of the Herpetoviridae family. Through these studies the ubiquity of EBV became evident, as did its relationship to human malignant and non-malignant diseases. Besides being linked etiologically with infectious mononucleosis, the Epstein-Barr virus is closely associated with Burkitt lymphoma and nasopharingeal carcinoma. In addition to the intrinsic value of the findings reported, these extremely important studies have also brought a better understanding of the possible mechanisms and affects of viral infections in man.

  18. Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase.

    Science.gov (United States)

    Murata, Takayuki; Isomura, Hiroki; Yamashita, Yoriko; Toyama, Shigenori; Sato, Yoshitaka; Nakayama, Sanae; Kudoh, Ayumi; Iwahori, Satoko; Kanda, Teru; Tsurumi, Tatsuya

    2009-06-20

    The Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial.

  19. Progress and problems in understanding and managing primary Epstein-Barr virus infections.

    Science.gov (United States)

    Odumade, Oludare A; Hogquist, Kristin A; Balfour, Henry H

    2011-01-01

    Epstein-Barr virus (EBV) is a gammaherpesvirus that infects a large fraction of the human population. Primary infection is often asymptomatic but results in lifelong infection, which is kept in check by the host immune system. In some cases, primary infection can result in infectious mononucleosis. Furthermore, when host-virus balance is not achieved, the virus can drive potentially lethal lymphoproliferation and lymphomagenesis. In this review, we describe the biology of EBV and the host immune response. We review the diagnosis of EBV infection and discuss the characteristics and pathogenesis of infectious mononucleosis. These topics are approached in the context of developing therapeutic and preventative strategies.

  20. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Rasmussen, N S; Nielsen, C T; Houen, G

    2016-01-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytom......We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse...... and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients...

  1. Detection of Human Cytomegalovirus and Epstein-Barr Virus in Coronary Atherosclerotic Tissue

    Science.gov (United States)

    Imbronito, Ana Vitória; Marcelino, Silvia Linardi; Grande, Sabrina Rosa; Nunes, Fabio Daumas; Romito, Giuseppe Alexandre

    2010-01-01

    Previous studies indicated that patients with atherosclerosis are predominantly infected by human cytomegalovirus (HCMV), but rarely infected by type 1 Epstein-Barr virus (EBV-1). In this study, atheromas of 30 patients who underwent aortocoronary bypass surgery with coronary endartherectomy were tested for the presence of these two viruses. HCMV occurred in 93.3% of the samples and EBV-1 was present in 50% of them. Concurrent presence of both pathogens was detected in 43.3% of the samples. PMID:24031529

  2. Parálisis facial bilateral secundaria a infección por virus de Epstein-Barr Bilateral facial palsy due to Epstein-Barr virus infection

    OpenAIRE

    M.E. Erro; J. Urriza; L. Gila; E. Orbara; I. G. de Gurtubay

    2010-01-01

    Nuestro objetivo es describir dos pacientes jóvenes con parálisis facial periférica bilateral. Ambos presentaron inicialmente afectación en un lado de la cara, seguida pocos días después de afectación contralateral junto con sintomatología compatible con infección aguda por el virus de Epstein-Barr, que se confirmó con la serología. Uno de los pacientes experimentó mejoría completa mientras que en el otro la recuperación fue lenta y quedaron secuelas permanentes. La lesión bilateral del nervi...

  3. Tracheal ulcer due to Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Ito, Takeo; Fujisaki, Hideaki; Nishio, Suehiro; Hiroshige, Shigeo; Miyazaki, Eishi; Kadota, Jun-ichi

    2014-03-01

    A 74-year-old man was referred to our hospital because of a tracheal stenosis circumscribed with soft tissue density and a left pulmonary nodule. Open biopsy of a right submandibular lymph node revealed diffuse large B-cell lymphoma, and the malignant cells were positive for Epstein-Barr virus gene products. Bronchofiberscopy revealed a tracheal necrotizing ulcer. After chemotherapy, the tracheal ulcer resolved. To our knowledge, this is the first report of a case of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly with a tracheal ulcer. © 2013 Published by The Japanese Respiratory Society on behalf of The Japanese Respiratory Society.

  4. High risk human papillomavirus and Epstein Barr virus in human breast milk.

    Science.gov (United States)

    Glenn, Wendy K; Whitaker, Noel J; Lawson, James S

    2012-09-01

    Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV) and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV) sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Standard (liquid) and in situ polymerase chain reaction (PCR) techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer.High risk human papillomavirus was identified in milk samples of 6 of 40 (15%) from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%). The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.

  5. High risk human papillomavirus and Epstein Barr virus in human breast milk

    Directory of Open Access Journals (Sweden)

    Glenn Wendy K

    2012-09-01

    Full Text Available Abstract Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid and in situ polymerase chain reaction (PCR techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15% from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%. Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.

  6. Cholangiocarcinoma with Lymphoepithelioma-like Component not Associated with Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Wen-Han Chang

    2015-12-01

    Full Text Available Lymphoepithelioma-like cholangiocarcinoma (LELCC is a rare variant of intrahepatic cholangiocarcinoma. We herein have reported an unusual case of LELCC in a 71-year-old Taiwanese women with cirrhotic liver disease and chronic hepatitis C. The patient's liver tumor was unexpectedly discovered during a regular abdominal ultrasound exam without obvious clinical symptoms and signs; she thereafter received surgical resection. Histologically, the liver tumor showed lymphoepithelial-like appearance and features of cholangiocarcinoma without association with Epstein-Barr virus (EBV. We maintained regular follow-up with the patient for 3 years, who at that time was alive without tumor recurrence.

  7. Inhibitory effects of lapachol derivatives on epstein-barr virus activation.

    Science.gov (United States)

    Sacau, Elisa Pérez; Estévez-Braun, Ana; Ravelo, Angel G; Ferro, Esteban A; Tokuda, Harunkuni; Mukainaka, Teruo; Nishino, Hoyoku

    2003-02-20

    Sixteen derivatives (2-17) synthesized from the naphthoquinone lapachol (1), were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. They exhibited a variety of inhibitory activities from very high to moderate, which allow us to suggest structure-activity relationships. Ten of these derivatives are reported for the first time, their structures being thoroughly determined by spectroscopic methods.

  8. Nonconvulsive Status Epilepticus Complicating Epstein-Barr Virus Encephalitis in a Child

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    Filippo Greco

    2014-01-01

    Full Text Available Children with acute encephalopathy show prolonged electrographic seizure activity consistent with nonconvulsive status epilepticus (NCSE. Pediatric NCSE is a heterogeneous clinical entity with poor outcome and different etiologies, including central nervous system infection, stroke, toxic-metabolic syndrome, and epileptic syndrome. We report a 4-year-old girl with seizure and behavioral changes in whom the analysis of cerebrospinal fluid by polymerase chain reaction was positive for Epstein-Barr virus. We emphasize the importance of electroencephalography (EEG, and particularly, of continuous EEG monitoring for early recognition and appropriate treatment of this condition.

  9. Epstein-Barr Virus-Positive Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation: Pathogenesis, Clinical Manifestations, Diagnosis, and Management

    NARCIS (Netherlands)

    Nijland, Marieke L.; Kersten, Marie José; Pals, Steven T.; Bemelman, Frederike J.; ten Berge, Ineke J. M.

    2016-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a potentially fatal complication after (solid organ) transplantation, which is highly associated with Epstein-Barr virus (EBV). The EBV-specific cytotoxic T cell response that is essential in controlling the virus in healthy individuals is

  10. Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Balderacchi Jasminka

    2011-05-01

    Full Text Available Abstract Introduction Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. Case Presentation We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. Conclusion To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

  11. (HHV6) et d'Epstein-Barr virus (EBV) par PCR en temps réel chez ...

    African Journals Online (AJOL)

    Diagnostic moléculaire du Cytomégalovirus (CMV), de l'herpès virus humain de type 6 (HHV6) et d'Epstein-Barr virus (EBV) par PCR en temps réel chez les femmes enceintes VIH séropositives et séronégatives à Ouagadougou, Burkina Faso.

  12. Herpesvirus pan encodes a functional homologue of BHRF1, the Epstein-Barr virus v-Bcl-2

    Directory of Open Access Journals (Sweden)

    Williams Tracey

    2005-02-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV latently infects about 90% of the human population and is associated with benign and malignant diseases of lymphoid and epithelial origin. BHRF1, an early lytic cycle antigen, is an apoptosis suppressing member of the Bcl-2 family. In vitro studies imply that BHRF1 is dispensable for both virus replication and transformation. However, the fact that BHRF1 is highly conserved not only in all EBV isolates studied to date but also in the analogous viruses Herpesvirus papio and Herpesvirus pan that infect baboons and chimpanzees respectively, suggests BHRF1 may play an important role in vivo. Results Herpesvirus papio BHRF1 has been shown to function in an analogous manner to EBV BHRF1 in response to DNA damaging agents in human keratinocytes. In this study we show that the heterologous expression of the previously uncharacterised Herpesvirus pan BHRF1 in the human Burkitt's lymphoma cell line Ramos-BL provides similar anti-apoptotic functions to that of EBV BHRF1 in response to apoptosis triggered by serum withdrawal, etoposide treatment and ultraviolet (UV radiation. We also map the amino acid changes onto the recently solved structure of the EBV BHRF1 and reveal that these changes are unlikely to alter the 3D structure of the protein. Conclusions These findings show that the functional conservation of BHRF1 extends to a lymphoid background, suggesting that the primate virus proteins interact with cellular proteins that are themselves highly conserved across the higher primates. Further weight is added to this suggestion when we show that the difference in amino acid sequences map to regions on the 3D structure of EBV BHRF1 that are unlikely to change the conformation of the protein.

  13. Cerebelite aguda causada por vírus Epstein-Barr: relato de caso Acute cerebellitis caused by Epstein-Barr virus: case report

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2001-09-01

    Full Text Available A cerebelite aguda pode ocorrer em associação a infecção pelo vírus da varicela-zoster, enterovirus, caxumba, micoplasma e outros agentes infecciosos. A cerebelite aguda é uma complicação rara da infecção pelo vírus Epstein-Barr (EBV. Relatamos o caso de uma mulher de 21 anos com história de 12 dias de evolução com náuseas, vômitos, ataxia de marcha e membros, tremor cefálico e de membros, opsoclono, mioclonias e rash cutâneo. Sorologia para EBV foi positiva. A infecção pelo EBV, com complicações neurológicas, pode não se apresentar com os sinais e sintomas clássicos da mononucleose infeciosa.Acute cerebellitis can occur in association with varicella-zoster virus, enterovirus, mumps, mycoplasma, and other infective organisms. Acute cerebellitis is a rare complication of Epstein-Barr virus (EBV infection. We report the case of a 21-year-old woman with a 12-day history of nausea and vomiting, gait and limbs ataxia, myoclonus, tremor of head and all four limbs, opsoclonus and cutaneous rash. Anti-EBV IgG and IgM antibodies against antiviral capsid were positive and anti-EBV against virus-associated nuclear antigen was also positive. EBV infection in association with neurological findings can occur without the classic signs and symptoms of infectious mononucleosis.

  14. Seroprevalence and real-time PCR study of Epstein-Barr virus and the value of screening in pretransplant patients

    Directory of Open Access Journals (Sweden)

    Mervat Elansary

    2016-01-01

    Routine screening for Epstein-Barr virus in blood bags is not economical. Screening is highly recommended only for immunocompromised and pretransplant patients. Viremia is not the role in individuals with EBV IgM positive sera, which in turn changes some concepts in organ transplantation.

  15. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.

    NARCIS (Netherlands)

    Urayama, K.Y.; Jarrett, R.F.; Hjalgrim, H.; Diepstra, A.; Kamatani, Y.; Chabrier, A.; Gaborieau, V.; Boland, A.; Nieters, A.; Becker, N.; Foretova, L.; Benavente, Y.; Maynadie, M.; Staines, A.; Shield, L.; Lake, A.; Montgomery, D.; Taylor, M.; Smedby, K.E.; Amini, R.M.; Adami, H.O.; Glimelius, B.; Feenstra, B.; Nolte, I.M.; Visser, L.; Imhoff, G.W. van; Lightfoot, T.; Cocco, P.; Kiemeney, L.A.; Vermeulen, S.; Holcatova, I.; Vatten, L.; Macfarlane, G.J.; Thomson, P.; Conway, D.I.; Benhamou, S.; Agudo, A.; Healy, C.M.; Overvad, K.; Tjonneland, A.; Melin, B.; Canzian, F.; Khaw, K.T.; Travis, R.C.; Peeters, P.H.M.; Gonzalez, C.A.; Quiros, J.R.; Sanchez, M.J.; Huerta, J.M.; Ardanaz, E.; Dorronsoro, M.; Clavel-Chapelon, F.; Bueno-De-Mesquita, H.B.; Riboli, E.; Roman, E.; Boffetta, P.; Sanjose, S. de; Zelenika, D.; Melbye, M.; Berg, A. van den; Lathrop, M.; Brennan, P.; McKay, J.D.

    2012-01-01

    BACKGROUND: Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification. METHODS: We conducted a genome-wide association study of

  16. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups

    NARCIS (Netherlands)

    Urayama, Kevin Y.; Jarrett, Ruth F.; Hjalgrim, Henrik; Diepstra, Arjan; Kamatani, Yoichiro; Chabrier, Amelie; Gaborieau, Valerie; Boland, Anne; Nieters, Alexandra; Becker, Nikolaus; Foretova, Lenka; Benavente, Yolanda; Maynadie, Marc; Staines, Anthony; Shield, Lesley; Lake, Annette; Montgomery, Dorothy; Taylor, Malcolm; Smedby, Karin Ekstrom; Amini, Rose-Marie; Adami, Hans-Olov; Glimelius, Bengt; Feenstra, Bjarke; Nolte, Ilja M.; Visser, Lydia; van Imhoff, Gustaaf W.; Lightfoot, Tracy; Cocco, Pierluigi; Kiemeney, Lambertus; Vermeulen, Sita H.; Holcatova, Ivana; Vatten, Lars; Macfarlane, Gary J.; Thomson, Peter; Conway, David I.; Benhamou, Simone; Agudo, Antonio; Healy, Claire M.; Overvad, Kim; Tjonneland, Anne; Melin, Beatrice; Canzian, Federico; Khaw, Kay-Tee; Travis, Ruth C.; Peeters, Petra H. M.; Gonzalez, Carlos A.; Quiros, Jose Ramon; Sanchez, Maria-Jose; Maria Huerta, Jose; Ardanaz, Eva; Dorronsoro, Miren; Clavel-Chapelon, Francoise; Bueno-de-Mesquita, H. Bas; Riboli, Elio; Roman, Eve; Boffetta, Paolo; de Sanjose, Silvia; Zelenika, Diana; Melbye, Mads; van den Berg, Anke; Lathrop, Mark; Brennan, Paul; McKay, James D.

    2012-01-01

    BACKGROUND: Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification. METHODS: We conducted a genome-wide association study of

  17. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    Science.gov (United States)

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Lundgren, Jens Dilling

    1991-01-01

    (6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0...

  19. (18)F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma

    DEFF Research Database (Denmark)

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on (18)F-FDG PET/CT mimicked malignant lymphoma. Follow-up (18)F-FDG PET/CT scan in the patient performed 7 weeks after...

  20. How compelling are the data for Epstein-Barr virus being a trigger for systemic lupus and other autoimmune diseases?

    DEFF Research Database (Denmark)

    Draborg, Anette; Gonzalez-Izarzugaza, Jose Maria; Houen, Gunnar

    2016-01-01

    Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental...

  1. Relationship of intratumoural protein expression patterns to age and Epstein-Barr virus status in classical Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Ludvigsen, Maja; Kamper, Peter; Hamilton-Dutroit, Stephen J

    2015-01-01

    In Western countries, the age distribution of Hodgkin lymphoma (HL) follows a characteristic bimodal curve showing an early and a late peak at approximately 35 and 70 yr, respectively. Furthermore, the presence of latent Epstein-Barr virus (EBV) genome in the Hodgkin Reed-Sternberg cells...

  2. Conjunctival tumor caused by Epstein-Barr virus-related infectious mononucleosis: Case report and review of literature.

    Science.gov (United States)

    Vaivanijkul, Juntarut; Boonsiri, Kreopun

    2017-04-01

    The conjunctival tumor associated with Epstein-Barr virus related infectious mononucleosis is a rare ocular manifestation. Only a few cases have been reported in the literature. We reported this rare condition that presented in a 5-year-old boy.

  3. Epstein-Barr Virus-Positive Mucocutaneous Ulcer Mimicking Rectal Carcinoma at 18F-FDG PET/CT.

    Science.gov (United States)

    Maffione, Anna Margherita; Rampin, Lucia; Paolini, Rossella; Rodella, Elisabetta; Lisato, Laura Camilla; Ballotta, Maria Rosa; Pavanato, Giovanni; Montesi, Giampaolo; Colletti, Patrick M; Rubello, Domenico

    2017-08-01

    We report focally intense F-FDG PET/CT rectal activity (SUVmax = 25) with a horseshoe distribution in an 81-year-old man with B-cell chronic lymphocytic leukemia and suspected Richter transformation. While imaging findings were typical for rectal adenocarcinoma, histology revealed Epstein-Barr virus-positive mucocutaneous ulcer.

  4. High prevalence of Epstein-Barr virus type 2 among homosexual men is caused by sexual transmission

    NARCIS (Netherlands)

    van Baarle, D.; Hovenkamp, E.; Dukers, N. H.; Renwick, N.; Kersten, M. J.; Goudsmit, J.; Coutinho, R. A.; Miedema, F.; van Oers, M. H.

    2000-01-01

    To investigate whether Epstein-Barr virus (EBV) type 2 infection is highly prevalent among homosexual men, the prevalence of EBV type 2 was studied among homosexual and heterosexual white men who were at high and low risk for sexually transmitted diseases; these data were correlated with sexual

  5. A pathologic study of Hodgkin's disease in Korea and its association with the Epstein-Barr virus infection

    NARCIS (Netherlands)

    Huh, J; Park, C; Juhng, S; Kim, Chi Eun; Poppema, Sibrand; Kim, Chulwoo

    1996-01-01

    BACKGROUND. The incidence of Hodgkin's disease (HD) in Korea and other Asian countries is much lower than in western countries and its association with the Epstein-Barr virus has not been well characterized. METHODS. We evaluated the clinical, morphologic, and immunohistochemical features of 87

  6. A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children With Chronic Kidney Disease Awaiting Transplantation

    NARCIS (Netherlands)

    Rees, L.; Tizard, E.J.; Morgan, A.J.; Cubitt, W.D.; Finerty, S.; Oyewole-Eletu, T.A.; Owen, K.; Royed, C.; Stevens, S.J.C.; Shroff, R.C.; Tanday, M.K.; Wilson, A.; Middeldorp, J.M.; Amlot, P.L.; Steven, N.M.

    2009-01-01

    Background. Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. Methods. A phase I trial recruited children with chronic

  7. Computational analysis of EBNA1 ``druggability'' suggests novel insights for Epstein-Barr virus inhibitor design

    Science.gov (United States)

    Gianti, Eleonora; Messick, Troy E.; Lieberman, Paul M.; Zauhar, Randy J.

    2016-04-01

    The Epstein-Barr Nuclear Antigen 1 (EBNA1) is a critical protein encoded by the Epstein-Barr Virus (EBV). During latent infection, EBNA1 is essential for DNA replication and transcription initiation of viral and cellular genes and is necessary to immortalize primary B-lymphocytes. Nonetheless, the concept of EBNA1 as drug target is novel. Two EBNA1 crystal structures are publicly available and the first small-molecule EBNA1 inhibitors were recently discovered. However, no systematic studies have been reported on the structural details of EBNA1 "druggable" binding sites. We conducted computational identification and structural characterization of EBNA1 binding pockets, likely to accommodate ligand molecules (i.e. "druggable" binding sites). Then, we validated our predictions by docking against a set of compounds previously tested in vitro for EBNA1 inhibition (PubChem AID-2381). Finally, we supported assessments of pocket druggability by performing induced fit docking and molecular dynamics simulations paired with binding affinity predictions by Molecular Mechanics Generalized Born Surface Area calculations for a number of hits belonging to druggable binding sites. Our results establish EBNA1 as a target for drug discovery, and provide the computational evidence that active AID-2381 hits disrupt EBNA1:DNA binding upon interacting at individual sites. Lastly, structural properties of top scoring hits are proposed to support the rational design of the next generation of EBNA1 inhibitors.

  8. Evasion of T cell immunity by Epstein-Barr virus

    NARCIS (Netherlands)

    Horst, D.

    2011-01-01

    Immune evasion strategies are thought to contribute essentially to the life cycle of persistent viruses by delaying the elimination of the infected cell long enough to enable the virus to replicate. Exemplary in this context are the herpesviruses, large DNA viruses that are carried as a persistent

  9. EVIDENCE OF EPSTEIN-BARR VIRUS ASSOCIATION WITH HEAD AND NECK CANCERS: A REVIEW.

    Science.gov (United States)

    Prabhu, Soorebettu R; Wilson, David F

    2016-01-01

    Epstein-Barr virus (EBV) is ubiquitous: over 90% of the adult population is infected with this virus. EBV is capable of infecting both B lymphocytes and epithelial cells throughout the body including the head and neck region. Transmission occurs mainly by exchange of saliva. The infection is asymptomatic or mild in children but, in adolescents and young adults, it causes infectious mononucleosis, a self-limiting disease characterized by lethargy, sore throat, fever and lymphadenopathy. Once established, the virus often remains latent and people become lifelong carriers without experiencing disease. However, in some people, the latent virus is capable of causing malignant tumours, such as nasopharyngeal carcinoma and various B- and T-cell lymphomas, at sites including the head, neck and oropharyngeal region. As lymphoma is the second-most common malignant disease of the head, neck and oral region after squamous cell carcinoma, oral health care workers including dentists and specialists have a responsibility to carry out a thorough clinical examination of this anatomical region with a view to identifying and diagnosing lesions that may represent lymphomas. Early detection allows early treatment resulting in better prognosis. The focus of this review is on the morphology, transmission and carcinogenic properties of EBV and clinical and diagnostic aspects of a range of EBV-associated malignancies occurring in the head, neck and oral region. As carcinogenic agents, viruses contribute to a significant proportion of the global cancer burden: approximately 15% of all human cancers, worldwide, are attributable to viruses.1,2 Serologic and epidemiologic studies are providing mounting evidence of an etiologic association between viruses and head and neck malignancies.3 To update oral and maxillofacial surgeons and oral medicine specialists and raise awareness of this association, we recently reviewed the evidence of the etiologic role of human papillomavirus in oral disease.4

  10. Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Hørding, U; Nielsen, H W

    1994-01-01

    Epidemiological features suggest that the risk of testicular cancer may be related to exposure to unknown infectious agents, including viruses. Therefore a series of twenty specimens of testicular germ cell tumours, including preinvasive carcinoma in-situ, were tested for the presence of DNA...... sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace...... that a significant direct involvement of HPV and EBV in human testicular germ cell carcinogenesis is unlikely. However, a putative growth-stimulating role of EBV-transformed lymphocytes, which are frequently present in the stromal tissues of testicular tumours, cannot be excluded....

  11. Regulation of Telomere Homeostasis during Epstein-Barr virus Infection and Immortalization.

    Science.gov (United States)

    Kamranvar, Siamak A; Masucci, Maria G

    2017-08-09

    The acquisition of unlimited proliferative potential is dependent on the activation of mechanisms for telomere maintenance, which counteracts telomere shortening and the consequent triggering of the DNA damage response, cell cycle arrest, and apoptosis. The capacity of Epstein Barr virus (EBV) to infect B-lymphocytes in vitro and transform the infected cells into autonomously proliferating immortal cell lines underlies the association of this human gamma-herpesvirus with a broad variety of lymphoid and epithelial cell malignancies. Current evidence suggests that both telomerase-dependent and -independent pathways of telomere elongation are activated in the infected cells during the early and late phases of virus-induced immortalization. Here we review the interaction of EBV with different components of the telomere maintenance machinery and the mechanisms by which the virus regulates telomere homeostasis in proliferating cells. We also discuss how these viral strategies may contribute to malignant transformation.

  12. Epstein-Barr virus latency type and spontaneous reactivation predict lytic induction levels.

    Science.gov (United States)

    Phan, An T; Fernandez, Samantha G; Somberg, Jessica J; Keck, Kristin M; Miranda, Jj L

    2016-05-20

    The human Epstein-Barr virus (EBV) evades the immune system by entering a transcriptionally latent phase in B cells. EBV in tumor cells expresses distinct patterns of genes referred to as latency types. Viruses in tumor cells also display varying levels of lytic transcription resulting from spontaneous reactivation out of latency. We measured this dynamic range of lytic transcription with RNA deep sequencing and observed no correlation with EBV latency types among genetically different viruses, but type I cell lines reveal more spontaneous reactivation than isogenic type III cultures. We further determined that latency type and spontaneous reactivation levels predict the relative amount of induced reactivation generated by cytotoxic chemotherapy drugs. Our work has potential implications for personalizing medicine against EBV-transformed malignancies. Identifying latency type or measuring spontaneous reactivation may provide predictive power in treatment contexts where viral production should be either avoided or coerced. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Therapeutic Strategies against Epstein-Barr Virus-Associated Cancers Using Proteasome Inhibitors.

    Science.gov (United States)

    Hui, Kwai Fung; Tam, Kam Pui; Chiang, Alan Kwok Shing

    2017-11-21

    Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers.

  14. Chromatin reorganisation in Epstein-Barr virus-infected cells and its role in cancer development.

    Science.gov (United States)

    West, Michelle J

    2017-10-01

    The oncogenic Epstein-Barr virus (EBV) growth transforms B cells and drives lymphoma and carcinoma development. The virus encodes four key transcription factors (EBNA2, EBNA3A, EBNA3B and EBNA3C) that hijack host cell factors to bind gene control elements and reprogramme infected B cells. These viral factors predominantly target long-range enhancers to alter the expression of host cell genes that control B cell growth and survival and facilitate virus persistence. Enhancer and super-enhancer binding by these EBNAs results in large-scale reorganisation of three-dimensional enhancer-promoter architecture to drive the overexpression of oncogenes, the silencing of tumour suppressors and the modulation of transcription, cell-cycle progression, migration and adhesion. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  15. Lymphocryptovirus phylogeny and the origins of Epstein-Barr virus

    DEFF Research Database (Denmark)

    Ehlers, Bernhard; Spiess, Katja; Leendertz, Fabian

    2010-01-01

    Specimens from wild and captive primates were collected and novel members of the genus Lymphocryptovirus (subfamily Gammaherpesvirinae) were searched for utilizing PCR for the DNA polymerase gene. Twenty-one novel viruses were detected. Together with previous findings, more than 50 distinct...... that evolutionary substitution in Clade B has proceeded more slowly than elsewhere in the LCV tree. It was estimated that in Clade B a subclade containing EBV, a gorilla virus and two chimpanzee viruses derived from an Old World monkey LCV line approximately 12 million years ago, and another subclade containing...

  16. Epstein-Barr virus growth/latency III program alters cellular microRNA expression

    International Nuclear Information System (INIS)

    Cameron, Jennifer E.; Fewell, Claire; Yin, Qinyan; McBride, Jane; Wang Xia; Lin Zhen

    2008-01-01

    The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers

  17. Epstein-Barr Virus and Its Association with Oral Hairy Leukoplakia: A Short Review

    Science.gov (United States)

    Khammissa, Razia Abdool Gafaar; Fourie, Jeanine; Chandran, Rakesh; Lemmer, Johan

    2016-01-01

    In immunocompromised subjects, Epstein-Barr virus (EBV) infection of terminally differentiated oral keratinocytes may result in subclinical productive infection of the virus in the stratum spinosum and in the stratum granulosum with shedding of infectious virions into the oral fluid in the desquamating cells. In a minority of cases this productive infection with dysregulation of the cell cycle of terminally differentiated epithelial cells may manifest as oral hairy leukoplakia. This is a white, hyperkeratotic, benign lesion of low morbidity, affecting primarily the lateral border of the tongue. Factors that determine whether productive EBV replication within the oral epithelium will cause oral hairy leukoplakia include the fitness of local immune responses, the profile of EBV gene expression, and local environmental factors. PMID:27047546

  18. Incidence of Epstein-Barr Virus in Astronaut Saliva During Spaceflight

    Science.gov (United States)

    Payne, Deborah A.; Mehta, Satish K.; Tyring, Stephen K.; Stowe, Raymond P.; Pierson, Duane L.

    1998-01-01

    Astronauts experience psychological and physical stresses that may result in re-activation of latent viruses during spaceflight, potentially increasing the risk of disease among crew members. The shedding of Epstein-Barr virus (EBV) in the saliva of astronauts will increase during spaceflight. A total of 534 saliva specimens were collected from 11 EBV-seropositive astronauts before, during, and after four space shuttle missions. The presence of EBV DNA in saliva, assessed by polymerase chain reaction (PCR), was used to determine shedding patterns before, during, and after spaceflight. EBV DNA was detected more frequently before flight than during (p less than 0.001) or after (p less than 0.01) flight. No significant difference between the in-flight and postflight periods was detected in the frequency of occurrence of EBV DNA. The increased frequency of shedding of EBV before flight suggests that stress levels may be greater before launch than during or after spaceflight.

  19. Space Flight-Induced Reactivation of Latent Epstein-Barr Virus

    Science.gov (United States)

    Stowe, Raymond P.; Barrett, Alan D. T.; Pierson, Duane L.

    2001-01-01

    Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. We hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B-lymphocytes. If increased virus production and clonal expansion of infected B-lymphocytes are detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease. More importantly, we will begin to understand the basic mechanisms involved in stress-induced reactivation of EBV in circulating B-lymphocytes.

  20. Epstein-Barr Virus Hijacks DNA Damage Response Transducers to Orchestrate Its Life Cycle.

    Science.gov (United States)

    Hau, Pok Man; Tsao, Sai Wah

    2017-11-16

    The Epstein-Barr virus (EBV) is a ubiquitous virus that infects most of the human population. EBV infection is associated with multiple human cancers, including Burkitt's lymphoma, Hodgkin's lymphoma, a subset of gastric carcinomas, and almost all undifferentiated non-keratinizing nasopharyngeal carcinoma. Intensive research has shown that EBV triggers a DNA damage response (DDR) during primary infection and lytic reactivation. The EBV-encoded viral proteins have been implicated in deregulating the DDR signaling pathways. The consequences of DDR inactivation lead to genomic instability and promote cellular transformation. This review summarizes the current understanding of the relationship between EBV infection and the DDR transducers, including ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), and DNA-PK (DNA-dependent protein kinase), and discusses how EBV manipulates the DDR signaling pathways to complete the replication process of viral DNA during lytic reactivation.

  1. Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species.

    Science.gov (United States)

    Zhang, Shilun; Yin, Juan; Zhong, Jiang

    2017-01-01

    Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L -1 ). The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine (NAC), an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

  2. Ascorbic acid kills Epstein-Barr virus positive Burkitt lymphoma cells and Epstein-Barr virus transformed B-cells in vitro, but not in vivo.

    Science.gov (United States)

    Shatzer, Amber N; Espey, Michael Graham; Chavez, Mayra; Tu, Hongbin; Levine, Mark; Cohen, Jeffrey I

    2013-05-01

    Ascorbic acid has been shown to kill various cancer cell lines at pharmacologic concentrations. We found that Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) cells were more susceptible to ascorbic acid-induced cell killing than EBV-negative BL cells or EBV-transformed lymphoblastoid cells (LCLs). Ascorbic acid did not induce apoptosis in any of the tested cells but did induce the production of reactive oxygen species and cell death. Previously, we showed that bortezomib, a proteasome inhibitor, induces cell death in LCLs and EBV-positive BL cells. We found that ascorbic acid is strongly antagonistic for bortezomib-induced cell death in LCLs and EBV-positive BL cells. Finally, ascorbic acid did not prolong survival of severe combined immunodefiency mice inoculated with LCLs either intraperitoneally or subcutaneously. Thus, while ascorbic acid was highly effective at killing EBV-positive BL cells and LCLs in vitro, it antagonized cell killing by bortezomib and was ineffective in an animal model.

  3. Advances in Virus-Directed Therapeutics against Epstein-Barr Virus-Associated Malignancies

    Directory of Open Access Journals (Sweden)

    Sajal K. Ghosh

    2012-01-01

    Full Text Available Epstein-Barr virus (EBV is the causal agent in the etiology of Burkitt’s lymphoma and nasopharyngeal carcinoma and is also associated with multiple human malignancies, including Hodgkin’s and non-Hodgkin’s lymphoma, and posttransplantation lymphoproliferative disease, as well as sporadic cancers of other tissues. A causal relationship of EBV to these latter malignancies remains controversial, although the episomic EBV genome in most of these cancers is clonal, suggesting infection very early in the development of the tumor and a possible role for EBV in the genesis of these diseases. Furthermore, the prognosis of these tumors is invariably poor when EBV is present, compared to their EBV-negative counterparts. The physical presence of EBV in these tumors represents a potential “tumor-specific” target for therapeutic approaches. While treatment options for other types of herpesvirus infections have evolved and improved over the last two decades, however, therapies directed at EBV have lagged. A major constraint to pharmacological intervention is the shift from lytic infection to a latent pattern of gene expression, which persists in those tumors associated with the virus. In this paper we provide a brief account of new virus-targeted therapeutic approaches against EBV-associated malignancies.

  4. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: response to HLH-04 treatment protocol.

    Science.gov (United States)

    Jiménez-Hernández, Elva; Martínez-Villegas, Octavio; Sánchez-Jara, Berenice; Martínez-Martell, María Angélica; Hernández-Sánchez, Beatriz; Loza-Santiaguillo, Paloma Del Rocío; Pedro-Matías, Eduardo; Arellano-Galindo, José

    Hemophagocytic syndrome, macrophage activation syndrome, reactive histiocytosis or hemophagocytic lymphohistiocytosis (HLH) represent a group of diseases whose common thread is reactive or neoplastic mononuclear phagocytic system cells and dendritic cell proliferation. We present a case of an HLH probably associated with Epstein-Barr virus (EBV) in a 4-year-old male patient treated with HLH-04 protocol. Viral etiology in HLH is well accepted. In this case, clinical picture of HLH was assumed secondary to EBV infection because IgM serology at the time of clinical presentation was the only positive factor in the viral panel. Diagnosis of HLH is the critical first step to successful treatment. The earlier it is identified, the less the tissue damage and reduced risk of multiple organ failure, which favors treatment response. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Prolonged hepatitis and jaundice: a rare complication of paediatric Epstein-Barr virus infection.

    Science.gov (United States)

    Tan, Zhen Han; Phua, Kong Boo; Ong, Christina; Kader, Ajmal

    2015-07-01

    We herein report the case of a 14-year-old girl with Epstein-Barr virus (EBV) infectious mononucleosis who developed prolonged hepatitis and jaundice. At presentation, she had tender hepatomegaly with a markedly deranged liver function test. Abdominal ultrasonography showed hepatomegaly and a thickened gallbladder wall. During the subsequent 11 weeks, her transaminases showed two further peaks, which corresponded with clinical deterioration. Her highest alanine transaminase level was 1,795 µ/L and total bilirubin level was 154 µmol/L. She recovered fully with conservative management. EBV-related liver involvement is typically mild and self-limiting. We believe that tender hepatomegaly and gallbladder thickening may be important predictors of significant liver involvement. Although multiple transaminase peaks may occur, we do not consider this an indication for antiviral or immunosuppressive therapy. In the absence of strong evidence supporting the use of any specific therapy, we recommend a conservative approach for an immunocompetent patient.

  6. Epstein-Barr Virus-Related Hemophagocytic Lymphohistiocytosis: Hematologic Emergency in the Critical Care Setting

    Directory of Open Access Journals (Sweden)

    Neda Hashemi-Sadraei

    2015-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a rare and potential life-threatening clinical syndrome that results from uncontrolled activation of the immune system. Secondary HLH, more commonly observed in adult patients, is seen in the context of underlying triggering conditions. Epstein-Barr virus (EBV has been recognized as the leading infectious cause and is associated with a poor outcome. As clinical and laboratory features of HLH could overlap with septic shock syndrome in most patients, the diagnosis of HLH, especially in adults, is the most challenging aspect of the disease that results in delayed recognition and treatment of rapidly progressive multiorgan system failure. We report a case of Hemophagocytic lymphohistiocytosis in a patient who presented with signs of septic shock syndrome and we review the literature on the topic.

  7. Progress, prospects, and problems in Epstein-Barr virus vaccine development.

    Science.gov (United States)

    Balfour, Henry H

    2014-06-01

    Epstein-Barr virus (EBV) is responsible for a farrago of acute and chronic human diseases including cancer. A prophylactic vaccine could reduce this disease burden. Several EBV vaccines have been given to humans but none has been sufficiently studied to establish safety and efficacy. EBV vaccine development has been hampered by the lack of an animal model other than subhuman primates, proprietary issues, selection of an appropriate adjuvant, and failure to reach consensus on what an EBV vaccine could or should actually achieve. A recent conference at the U.S. National Institutes of Health emphasizing the global importance of EBV vaccine and advocating a phase 3 trial to prevent infectious mononucleosis should encourage research that could eventually lead to its licensure. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Circulating epstein-barr virus in children living in malaria-endemic areas

    DEFF Research Database (Denmark)

    Rasti, N; Falk, K I; Donati, D

    2005-01-01

    Children living in malaria-endemic regions have high incidence of Burkitt's lymphoma (BL), the aetiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. Acute malarial infection impairs the EBV-specific immune responses with the consequent increase...... in the number of EBV-carrying B cells in the circulation. To further understand the potential influence of malarial infection on the EBV persistence in children living in malaria-endemic areas, we studied the occurrence and quantified cell-free EBV-DNA in plasma from 73 Ghanaian children with and without acute...... malarial infection. Viral DNA was detected in 40% of the samples (47% in the malaria-infected and 34% in the nonmalaria group) but was absent in plasma from Ghanaian adults and healthy Italian children. These findings provide evidence that viral reactivation is common among children living in malaria...

  9. Cholecystitis and nephrotic syndrome complicating Epstein-Barr virus primary infection.

    Science.gov (United States)

    Rodà, Diana; Huici, Malka; Ricart, Sílvia; Vila, Jordi; Fortuny, Clàudia; Alsina, Laia

    2017-02-01

    Epstein-Barr virus (EBV) infection results in a spectrum of clinical manifestations. The host immune response to EBV plays a key role in the extent and degree of clinical features, which in children under 4 years of age are usually mild, non-specific and self-limiting. A 2-year-old boy in whom no known immune disorder could be found presented with acute acalculous cholecystitis, renal dysfunction with massive proteinuria, ascites, pleural effusion, minimal peripheral oedema and a severe systemic inflammatory response. Improvement occurred after initiation of corticosteroids and antiviral treatment with gancyclovir. In severely symptomatic or complicated EBV infection, a primary immunodeficiency must be suspected. If a primary immunodeficiency has been ruled out, the correct management of severe EBV infection in the immunocompetent host remains controversial.

  10. Imaging findings of epstein-barr virus-associated gastric lymphoepithelioma-Llke carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Tae Sun; KIm, Young Chul; Lee, Dakeun; Park, Mee Jin; Lee, Jei Hee; Kim, Kai Keun [Ajou University School of Medicine, Suwon (Korea, Republic of); Chung, Yong En [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-01-15

    To analyze the computed tomography (CT) features of Epstein-Barr virus (EBV)-associated lymphoepithelioma-like carcinoma (LELC). Between January 2004 and September 2014, radiologic features of 44 EBV-associated LELCs were analyzed. Lesion detectability, multiplicity, location, gross appearance, lesion thickness and margin, presence of a round edge, contrast enhancement pattern, and the degree of contrast enhancement were analyzed. The most common location of LELC was the upper third of the stomach (n = 28; 63.64%). A high percentage of cases showed uniform peripheral thickness (n = 32; 88.89%). LELCs demonstrated well-defined margins in a high percentage of cases (n = 31; 86.11%). Additionally, a high percentage of cases showed the presence of a round edge (n = 28; 77.78%). CT features, including tumor location in the upper third of the stomach and presence of uniform peripheral thickness with a round edge, may suggest the possibility of EBV-associated LELC.

  11. Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma.

    Science.gov (United States)

    Nakanishi, Yosuke; Wakisaka, Naohiro; Kondo, Satoru; Endo, Kazuhira; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Yoshizaki, Tomokazu

    2017-09-01

    Nasopharyngeal carcinoma (NPC) is very common in southern China and Southeast Asia. In regions where NPC is endemic, undifferentiated subtypes constitute most cases and are invariably associated with Epstein-Barr virus (EBV) infection, whereas the differentiated subtype is more common in other parts of the world. Undifferentiated NPC is a unique malignancy with regard to its epidemiology, etiology, and clinical presentation. Clinically, NPC is highly invasive and metastatic, but sensitive to both chemotherapy and radiotherapy (RT). Overall prognosis has dramatically improved over the past three decades because of advances in management, including the improvement of RT technology, the broader application of chemotherapy, and more accurate disease staging. Despite the excellent local control with modern RT, distant failure remains a challenging problem. Advances in molecular technology have helped to elucidate the molecular pathogenesis of NPC. This article reviews the contribution of EBV gene products to NPC pathogenesis and the current management of NPC.

  12. The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation

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    Ai-Di Gu

    2012-10-01

    Full Text Available Epstein-Barr virus (EBV is associated with nasopharyngeal carcinoma (NPC, but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1 epidemiological studies should reveal EBV infection as a risk factor; (2 the introduction of EBV into an animal model should produce NPC; (3 in the animal model NPC, the main molecular event(s or the involved signaling pathway(s should be identical to that in human NPC; and (4 finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.

  13. Bromodomain and extraterminal inhibitors block the Epstein-Barr virus lytic cycle at two distinct steps.

    Science.gov (United States)

    Keck, Kristin M; Moquin, Stephanie A; He, Amanda; Fernandez, Samantha G; Somberg, Jessica J; Liu, Stephanie M; Martinez, Delsy M; Miranda, Jj L

    2017-08-11

    Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. Proteins in the bromodomain and extraterminal (BET) family regulate multiple stages of viral life cycles and provide promising intervention targets. Synthetic small molecules can bind to the bromodomains and disrupt function by preventing recognition of acetylated lysine substrates. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV lytic cycle. BET inhibitors prevent expression of the viral immediate-early protein BZLF1. JQ1 alters transcription of genes controlled by the host protein BACH1, and BACH1 knockdown reduces BZLF1 expression. BET proteins also localize to the lytic origin of replication (OriLyt) genetic elements, and BET inhibitors prevent viral late gene expression. There JQ1 reduces BRD4 recruitment during reactivation to preclude replication initiation. This represents a rarely observed dual mode of action for drugs.

  14. Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal.

    Science.gov (United States)

    Serafini, Barbara; Scorsi, Eleonora; Rosicarelli, Barbara; Rigau, Valérie; Thouvenot, Eric; Aloisi, Francesca

    2017-06-15

    Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal is a potentially life-threatening event. To verify whether highly destructive inflammation after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient who died during a fulminating MS relapse following natalizumab withdrawal. Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white matter lesions; the highest frequency of EBV lytically infected cells and granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These results may encourage switching to B-cell depleting therapy after natalizumab discontinuation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Coinfection of Plasmodium vivax and Epstein-Barr virus: case report

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    Fatih Akin

    2013-02-01

    Full Text Available Malaria is an acute and chronic illness characterized by paroxysms of fever, chills, sweats, fatigue, anemia, and splenomegaly. It is still an important health problem in malaria-endemic countries. Children living in malaria-endemic areas have elevated Epstein-Barr Virus (EBV loads in the circulation and acute malaria infection leads to increased levels of circulating EBV that are cleared after anti-malaria treatment. There are many reports about the association of Plasmodium falciparum (P. falciparum malaria and EBV infection. Here we report a case who had coinfection of Plasmodium vivax (P. vivax malaria and EBV infection. To the best of our knowledge this is the first case indicating the association of P. vivax malaria and EBV infection.

  16. Hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus in the central nervous system.

    Science.gov (United States)

    Magaki, Shino; Ostrzega, Nora; Ho, Elliot; Yim, Catherine; Wu, Phillis; Vinters, Harry V

    2017-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare immune hyperactivation syndrome which may be primary (genetic) or secondary to various immune-related conditions including infection, immunodeficiency, and malignancies. Rapid diagnosis and treatment are essential because it can be associated with significant morbidity and mortality. Epstein-Barr virus (EBV) is a known infectious cause of acquired HLH, but EBV-associated HLH involving the central nervous system is rare and not well characterized neuropathologically. We report a case of fatal EBV-associated HLH with severe involvement of the central nervous system showing florid hemophagocytosis in the choroid plexus, with extensive neuron loss and gliosis in the cerebrum, cerebellum, and brainstem. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Acute acalculous cholecystitis by Epstein-Barr virus infection: a rare association

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    Liliana Branco

    2015-12-01

    Full Text Available Acute acalculous cholecystitis (AAC is a rare complication of Epstein Barr virus (EBV infection, with only a few cases reported among pediatric population. This clinical condition is frequently associated with a favorable outcome and, usually, a surgical intervention is not required. We report a 16-year-old girl who presented with AAC following primary EBV infection. The diagnosis of AAC was documented by clinical and ultrasonographic examination, whereas EBV infection was confirmed serologically. A conservative treatment was performed, with a careful monitoring and serial ultrasonographic examinations, which led to the clinical improvement of the patient. Pediatricians should be aware of the possible association between EBV and AAC, in order to offer the patients an appropriate management strategy.

  18. A method for evaluating antiviral drug susceptibility of Epstein-Barr virus

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    Charlotte A Romain

    2010-01-01

    Full Text Available Charlotte A Romain1, Henry H Balfour Jr1,2, Heather E Vezina1,3, Carol J Holman11Department of Laboratory Medicine and Pathology, 2Department of Pediatrics, 3Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USAAbstract: We developed an in vitro Epstein-Barr virus (EBV drug susceptibility assay using P3HR1 cells or lymphoblastoid cells from subjects with infectious mononucleosis, which were grown in the presence of various concentrations of acyclovir (ACV, ganciclovir (GCV or R-9-[4-hydroxy-2-(hydroxymethylbutyl]guanine (H2G and 12-O-tetradecanoyl-phorbol-13-acetate (TPA. On day 7, total cellular DNA was extracted and EBV DNA was detected using an in-house quantitative real-time polymerase chain reaction (PCR method. All three drugs had in vitro activity against EBV in both the laboratory standard producer cell line P3HR1 and in subject-derived lymphoblastoid cell lines. The median 50% inhibitory concentrations (IC50s in P3HR1 cells were: ACV, 3.4 μM; GCV, 2.6 μM; and H2G, 2.7 μM and in 3 subject-derived cells were: ACV, 2.5 μM; GCV, 1.7 μM; and H2G, 1.9 μM. Our assay can be used to screen candidate anti-EBV drugs. Because we can measure the IC50 of patients’ strains of EBV, this assay may also be useful for monitoring viral resistance especially in immunocompomised hosts receiving antiviral drugs for prevention or treatment of EBV diseases.Keywords: Epstein-Barr virus, ganciclovir, acyclovir, valomaciclovir, H2G, antivirals

  19. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study.

    Science.gov (United States)

    Langer-Gould, Annette; Wu, Jun; Lucas, Robyn; Smith, Jessica; Gonzales, Edlin; Amezcua, Lilyana; Haraszti, Samantha; Chen, Lie Hong; Quach, Hong; James, Judith A; Barcellos, Lisa F; Xiang, Anny H

    2017-09-26

    To determine whether Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositivity is associated with multiple sclerosis (MS) in blacks and Hispanics and to what extent measures of the hygiene hypothesis or breastfeeding could explain these findings. EBV and CMV have been associated with MS risk in whites, and the timing and frequency of both viruses vary by factors implicated in the hygiene hypothesis. Incident cases of MS or its precursor, clinically isolated syndrome (CIS), and matched controls (blacks, 111 cases/128 controls; Hispanics, 173/187; whites, 235/256) were recruited from the membership of Kaiser Permanente Southern California. Logistic regression models accounted for HLA-DRB1*1501 status, smoking, socioeconomic status, age, sex, genetic ancestry, and country of birth. Epstein-Barr nuclear antigen-1 (EBNA-1) seropositivity was independently associated with an increased odds of MS/CIS in all 3 racial/ethnic groups ( p < 0.001 for blacks and whites, p = 0.02 for Hispanics). In contrast, CMV seropositivity was associated with a lower risk of MS/CIS in Hispanics ( p = 0.004) but not in blacks ( p = 0.95) or whites ( p = 0.96). Being born in a low/middle-income country was associated with a lower risk of MS in Hispanics ( p = 0.02) but not after accounting for EBNA-1 seropositivity. Accounting for breastfeeding did not diminish the association between CMV and MS in Hispanics. The consistency of EBNA-1 seropositivity with MS across racial/ethnic groups and between studies points to a strong biological link between EBV infection and MS risk. The association between past CMV infection and MS risk supports the broader hygiene hypothesis, but the inconsistency of this association across racial/ethnic groups implies noncausal associations. © 2017 American Academy of Neurology.

  20. Epstein-Barr virus in oral mucosa from human immunodeficiency virus positive patients

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    Larissa Santos

    2014-06-01

    Full Text Available Objective: the detection rate of Epstein-Barr virus (EBV is higher in people living with human immunodeficiency virus (HIV. In an attempt to contribute to our epidemiological understanding of this coinfection and to investigate the activity of EBV in normal oral mucosa, we performed a cross-sectional study with HIV-positive patients. Methods: oral smears from 145 HIV-positive patients were collected between March 2010 and March 2011. Nested polymerase chain reaction (PCR and reverse transcriptase-PCR (RT-PCR were used to genotype EBV and to detect EBNA-2 expression, respectively. Results: EBV DNA was detected in 48.3% of the study participants, of whom 32.85% were EBV-1 and 45.71% were EBV-2 carriers. Additionally, 14.28% were coinfected with both types. EBNA-2 mRNA was expressed in 45.7% of the EBV -positive samples, including 20.0% with EBV-1 only, 20.0% with EBV-2 only and 1.4% with both genotypes. Immune status affected the overall EBV infection, and EBV-2 positivity was significantly correlated with sexual lifestyle of the participants. EBV co-infection with both viral types was dependent upon HIV viral load and the activity of the EBNA-2 gene. Conclusion: we report a high prevalence of active EBV in the oral mucosa of asymptomatic HIV-seropositive individuals. This study addresses the need for monitoring and treatment of HIV-infected patients with EBV reactivation.

  1. Virus-specific cytotoxic T cells in chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Shibayama, Haruna; Imadome, Ken-Ichi; Onozawa, Erika; Tsuzura, Akiho; Miura, Osamu; Koyama, Takatoshi; Arai, Ayako

    2017-01-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a disease characterized by clonally proliferating and activated EBV-infected T or NK cells accompanied by chronic inflammation and T- or NK-cell neoplasms. However, the mechanism for developing CAEBV has not been clarified to date. Because the decreased number or inactivation of EBV-specific cytotoxic T lymphocytes (CTLs) resulted in the development of EBV-positive B-cell neoplasms, we investigated the number of CTLs in CAEBV patients using the tetrameric complexes of HLA-restricted EBV-specific peptides. Among the seven patients examined, EBV-specific CTLs were detected in the peripheral blood mononuclear cells (PBMCs) of four cases but were not detected in three cases. The ratio of EBV-specific CTLs in PBMCs tended to be higher in the patients with active disease than in those with inactive disease. In two patients in whom EBV-specific CTLs had not been detected, CTLs appeared after the eradication of EBV-infected T cells by allogeneic bone marrow transplantation. These results suggested that the failure of CTLs had a role in developing CAEBV, although the induction number and function of EBV-specific CTLs might vary in each patient.

  2. Detecção do vírus Epstein-Barr em tonsilites recorrentes Detection of Epstein-Barr virus in recurrent tonsillitis

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    Eliane Pedra Dias

    2009-02-01

    Full Text Available As tonsilites recorrentes têm sido objeto de muitos estudos. Eventos considerados na predisposição e causa incluem a utilização errônea de antibióticos em crises agudas, alterações da microflora, mudanças estruturais nas criptas epiteliais tonsilares e infecções virais. A infecção pelo vírus Epstein-Barr (EBV ocorre freqüentemente na infância persistindo em linfócitos de tonsilas, podendo causar tonsilites recorrentes. Pouco se conhece sobre a persistência e reativação do EBV em pacientes imunocompetentes. Alguns métodos como a hibridização in situ, a reação em cadeia da polimerase (PCR e a imuno-histoquímica têm sido utilizados no estudo da patogenia do vírus. OBJETIVO: Para caracterizar a associação do vírus Epstein-Barr com tonsilites recorrentes examinamos a presença do EBV pela PCR e por imuno-histoquímica usando como alvo a proteína viral LMP-1. FORMA DE ESTUDO: Estudo transversal com análise de prevalência amostral. MATERIAL E MÉTODOS: Foram selecionados 24 blocos parafinados de tonsilas, provenientes do Serviço de Anatomia Patológica, removidas de crianças de 2 a 12 anos com diagnóstico de tonsilite recorrente. Resultados: O genoma do EBV foi detectado em 13 (54,1% e a LMP-1 em 9 (37,5% dos casos. CONCLUSÃO: As tonsilas das crianças podem ser colonizadas pelo EBV e este pode estar associado à patogenia das tonsilites recorrentes.Recurrent tonsillitis has been the subject of frequent investigation. Misuse of antibiotic therapy in acute tonsillitis, changes to the tonsillar microflora, structural changes to the tonsillar crypts, and viral infections have been listed as predisposing or causal factors for recurrent tonsillitis. Epstein-Barr virus (EBV infection usually occurs in early childhood and may persist in tonsillar lymphocytes, thus leading to the onset of recurrent tonsillitis. Little is known about the persistence and reactivation of EBV strains in immunocompetent patients. Methods such

  3. Pathogenesis of virus-associated human cancers: Epstein-Barr virus and hepatitis B virus as two examples.

    Science.gov (United States)

    Chang, Kung-Chao; Chang, Yao; Wang, Lily Hui-Ching; Tsai, Hung-Wen; Huang, Wenya; Su, Ih-Jen

    2014-09-01

    Virus-associated human cancers may exhibit two characteristic histopathologic features: (1) the inflammation-rich background as observed in Epstein-Barr virus-associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC); and (2) the characteristic nuclear morphology such as the Reed-Sternberg cells in HL. Besides, the hepatocytes of chronic hepatitis B virus (HBV) infection frequently exhibit characteristic ground glass hepatocytes, a phenomenon associated with endoplasmic reticulum stress response induced by the overloaded or malfolded HBV surface antigens. In this review, we explore specifically the pathogenesis of Epstein-Barr virus-associated HL and NPC, and HBV-associated hepatocellular carcinoma based on the observed histopathologic features. We propose that the retention of viral proteins induces inflammation, endoplasmic reticulum stress, and genomic instability in HL, NPC, and hepatocellular carcinoma, whereby the viral oncoproteins may play additional transactivational roles to induce host genes for transformation, invasion, and metastasis. Therapeutic implications based on the pathogenesis of virus-associated cancers are discussed. Copyright © 2013. Published by Elsevier B.V.

  4. Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

    Science.gov (United States)

    Yao, Ji-Jin; Lin, Li; Jin, Ya-Nan; Wang, Si-Yang; Zhang, Wang-Jian; Zhang, Fan; Zhou, Guan-Qun; Cheng, Zhi-Bin; Qi, Zhen-Yu; Sun, Ying

    2017-08-01

    Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P 1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. Systemic Epstein-Barr Virus-positive T-Cell Lymphoproliferative Disease of Childhood With Good Response to Steroid Therapy.

    Science.gov (United States)

    Kim, Do-Hoon; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Han, Eunhee; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin

    2017-11-01

    Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare disease and has a very fulminant clinical course with high mortality. A 21-month-old female patient was referred to our hospital with a 1 week history of fever and was subsequently diagnosed with systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood. After starting treatment with dexamethasone, she showed early defervescence and improvement of laboratory parameters, and has remained disease-free after stopping steroid treatment, although longer follow-up is necessary. Our report underscores the possibility that this disease entity may be heterogenous in terms of prognosis.

  6. Study of the titers of Anti-Epstein-Barr virus antibodies in the sera of atomic bomb survivors

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi; Kusunoki, Yoichiro; Kyoizumi, Seishi; Ozaki, Kyoko; Mizuno, Shoichi; Cologne, J.B.

    1993-01-01

    Antibody titers to Epstein-Barr virus antigens were determined in the sera of 372 atomic bomb survivors to evaluate the effect of the previous radiation exposure on immune competence against the latent infection of the virus. The proportion of persons with high titers (≥ 1:40) of IgG antibodies to the early antigen was significantly elevated in the exposed survivors. Furthermore, the distribution of IgM titers against the viral capsid antigen was significantly affected by radiation dose with an increased occurrence of titers of 1:5 and 1:10 in the exposed persons, although the dose effect was only marginally suggestive when persons with rheumatoid factor were eliminated from the analysis. These results suggest that reactivation of Epstein-Barr virus in the latent stage occurs more frequently in the survivors, even though this might not be affected by the radiation dose. Otherwise, there was neither an increased trend in the prevalence of high titers (≥ 1:640) of IgG antibodies to the viral capsid antigen among the exposed people nor a correlation between the radiation exposure and distributions of titers of IgA antibodies to the viral capsid antigen or antibodies to the anti-Epstein-Barr virus-associated nuclear antigen. (author)

  7. Immune profile and Epstein-Barr virus infection in acute interstitial nephritis: an immunohistochemical study in 78 patients.

    LENUS (Irish Health Repository)

    Mansur, Abdurrezagh

    2011-01-01

    Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and is characterised by a dense interstitial cellular infiltrate, which has not been well defined. Previous studies have demonstrated a correlation between Epstein-Barr virus (EBV) infection and AIN. The purpose of our study was to define the nature of the interstitial immune infiltrate and to investigate the possibility of renal infection with EBV.

  8. Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report.

    Science.gov (United States)

    Engelmann, Ilka; Nasser, Hala; Belmiloudi, Soufien; Le Guern, Rémi; Dewilde, Anny; Vallée, Louis; Hober, Didier

    2013-06-01

    A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare complication of infectious mononucleosis. The severe clinical picture and the marked neuroimaging changes were in contrast with mild cerebrospinal fluid abnormalities: leukocyte count was normal and protein level was only slightly elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain reaction. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Multiple Evanescent White Dot Syndrome following Acute Epstein-Barr Virus Infection.

    Science.gov (United States)

    Yang, Chang-Sue; Hsieh, Ming-Hung; Su, Huan-I; Kuo, Yih-Shiuan

    2017-10-11

    To investigate the association between multiple evanescent white dot syndrome (MEWDS) and Epstein-Barr (EB) virus infection. A prospective, consecutive case series study was performed in patients with the characteristic findings of MEWDS. Patients received EB viral-specific antibody serologic tests. Five cases of MEWDS who had prodromal flu-like symptoms were enrolled, comprising 2 women and 3 men with a mean age of 34. Mean diopter of myopia was -7.5. During acute onset of MEWDS, EB virus infection was confirmed by positive EB virus serology test. One showed positive EB viral capsid antigen (EB-VCA) IgM, and the other four showed highly elevated titer of EB-VCA IgG more than 1:160. Two months later, paired serum virus serology data showed negative EB-VCA IgM, or prior EB-VCA IgG titer decreased four-fold in the recovery stage. MEWDS may be associated with acute systemic EB virus infection. Ocular symptoms might develop due to this infection or represent virus-induced autoimmune inflammatory retinitis.

  10. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    2009-09-01

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  11. DNA Epstein-Barr virus (EBV sebagai biomaker diagnosis karsinoma nasofaring

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    Janti Sudiono

    2013-09-01

    Full Text Available Background: Nasopharyngeal carcinoma (NPC is a malignant neoplasm arising from the mucosal epithelium of the nasopharynx with various cells differentiation. Nasopharyngeal carcinoma is vastly more common in certain regions of East Asia, South Asia and Africa with viral, dietary which is typically includes consumption of salted vegetables, fish, meat and genetic factors that implicated in its causation. The undifferentiated is the most common type of NPC and strongly associated with Epstein-Barr virus (EBV infection. Purpose: This paper was aimed to review about molecular biomarker as non invasive diagnosis of NPC especially in related to EBV infection in nasopharyngeal epithelial cells. Reviews: The pathogenesis of NPC particularly the endemic type seems to follow a multi-step process, in which EBV, ethnic background, and environmental carcinogens all seem to play important role. EBV DNA plasm level is used continuously in clinic as a promise, sensitive and specific molecular marker diagnostic that reflected the stage, treatment response and prognosis of NPC. Detection of nuclear antigen associated with Epstein-Barr virus (EBNA and viral DNA has revealed that EBV can infect epithelial cells and associated with their transformation in carcinogenesis. Latent membrane protein (LMP-1 and LMP-2 oncogenes EBV encoded related to proliferative gene expression indicated invasive and progressive growth of NPC. Conclusion: The new biomarkers for NPC, including EBV DNA in serum; EBV DNA and BamH1-A Reading Frame-1 (BARF1 mRNA in NPC brushings have been developed for the molecular non invasive diagnosis of this tumour.Latar belakang: Nasopharyngeal carcinoma (NPC, sering dikenal sebagai kanker nasofaring merupakan tumor ganas yang berasal dari epitel mukosa nasofaring dengan derajat diferensiasi sel yang bervariasi. Paling banyak ditemukan di Asia Selatan, Asia Timur, dan Afrika. Virus, pola diet tipikal seperti konsumsi sayuran, ikan dan daging yang

  12. Association between human papilloma virus/Epstein-Barr virus coinfection and oral carcinogenesis.

    Science.gov (United States)

    Jiang, Ru; Ekshyyan, Oleksandr; Moore-Medlin, Tara; Rong, Xiaohua; Nathan, Sean; Gu, Xin; Abreo, Fleurette; Rosenthal, Eben L; Shi, Mingxia; Guidry, Joseph T; Scott, Rona S; Hutt-Fletcher, Lindsey M; Nathan, Cherie-Ann O

    2015-01-01

    The recent epidemic of head and neck squamous cell carcinomas associated with human papilloma virus (HPV) has not addressed its association with lymphoid tissue in the oropharynx or the potential role of Epstein-Barr virus (EBV)/HPV coinfection. The prevalence of HPV and EBV infection/coinfection and CD21 mRNA expression were determined in normal and cancerous tissues from the oropharynx using in situ hybridization (ISH), p16, and quantitative reverse transcriptase PCR (qRT-PCR). The effects of coinfection on tumorigenicity were evaluated using proliferation and invasion assays. Normal oropharynx, tonsil, non-cancer base of tongue (BOT), and BOT from sleep apnea patients demonstrated EBV positivity ranging from 7% to 36% depending on the site and methods of detection used (qRT-PCR or ISH). Among non-malignant BOT samples, HPV positivity was noted only in 20%. The percent of tonsil and BOT cancers positive for HPV (up to 63% and 80%, respectively) or coinfected with HPV/EBV (up to 25% and 70%, respectively) were both significantly associated with cancer status. Notably, HPV/EBV coinfection was observed only in malignant tissue originating in lymphoid-rich oropharynx sites (tonsil, BOT). CD21 mRNA (the major EBV attachment receptor) was detected in tonsil and BOT epithelium, but not in soft-palate epithelium. Coinfected cell lines showed a significant increase in invasiveness (P < 0.01). There is a high prevalence of HPV/EBV infection and coinfection in BOT and tonsil cancers, possibly reflecting their origins in lymphoid-rich tissue. In vitro, cells modeling coinfection have an increased invasive potential. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas.

    Science.gov (United States)

    Armero, Victoria E S; Tremblay, Marie-Pier; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Duval, Cyntia; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S; Bisaillon, Martin

    2017-01-01

    Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein-Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.

  14. Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B

    Energy Technology Data Exchange (ETDEWEB)

    Backovic, Marija [Northwestern Univ., Evanston, IL (United States); Longnecker, Richard [Northwestern Univ., Chicago, IL (United States); Jardetzky, Theodore S [Northwestern Univ., Evanston, IL (United States)

    2009-03-16

    Epstein-Barr virus (EBV) is a herpesvirus that is associated with development of malignancies of lymphoid tissue. EBV infections are life-long and occur in >90% of the population. Herpesviruses enter host cells in a process that involves fusion of viral and cellular membranes. The fusion apparatus is comprised of envelope glycoprotein B (gB) and a heterodimeric complex made of glycoproteins H and L. Glycoprotein B is the most conserved envelope glycoprotein in human herpesviruses, and the structure of gB from Herpes simplex virus 1 (HSV-1) is available. Here, we report the crystal structure of the secreted EBV gB ectodomain, which forms 16-nm long spike-like trimers, structurally homologous to the postfusion trimers of the fusion protein G of vesicular stomatitis virus (VSV). Comparative structural analyses of EBV gB and VSV G, which has been solved in its pre and postfusion states, shed light on gB residues that may be involved in conformational changes and membrane fusion. Also, the EBV gB structure reveals that, despite the high sequence conservation of gB in herpesviruses, the relative orientations of individual domains, the surface charge distributions, and the structural details of EBV gB differ from the HSV-1 protein, indicating regions and residues that may have important roles in virus-specific entry.

  15. Identification of Epstein-Barr Virus Replication Proteins in Burkitt’s Lymphoma Cells

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    Chris Traylen

    2015-10-01

    Full Text Available The working model to describe the mechanisms used to replicate the cancer-associated virus Epstein-Barr virus (EBV is partly derived from comparisons with other members of the Herpes virus family. Many genes within the EBV genome are homologous across the herpes virus family. Published transcriptome data for the EBV genome during its lytic replication cycle show extensive transcription, but the identification of the proteins is limited. We have taken a global proteomics approach to identify viral proteins that are expressed during the EBV lytic replication cycle. We combined an enrichment method to isolate cells undergoing EBV lytic replication with SILAC-labeling coupled to mass-spectrometry and identified viral and host proteins expressed during the OPEN ACCESS Pathogens 2015, 4 740 EBV lytic replication cycle. Amongst the most frequently identified viral proteins are two components of the DNA replication machinery, the single strand DNA binding protein BALF2, DNA polymerase accessory protein BMRF1 and both subunits of the viral ribonucleoside-diphosphate reductase enzyme (BORF2 and BaRF1. An additional 42 EBV lytic cycle proteins were also detected. This provides proteomic identification for many EBV lytic replication cycle proteins and also identifies post-translational modifications.

  16. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts

    Science.gov (United States)

    Stowe, R. P.; Pierson, D. L.; Barrett, A. D.

    2001-01-01

    OBJECTIVE: The objective of this study was to determine the effects of stress and spaceflight on levels of neuroendocrine hormones and Epstein-Barr virus (EBV)-specific antibodies in astronauts. METHODS: Antiviral antibody titers and stress hormones were measured in plasma samples collected from 28 astronauts at their annual medical exam (baseline), 10 days before launch (L-10), landing day (R+0), and 3 days after landing (R+3). Urinary stress hormones were also measured at L-10 and R+0. RESULTS: Significant increases (p virus capsid antigen antibodies were found at all three time points (L-10, R+0, and R+3) as compared with baseline samples. Anti-EBV nuclear antigen antibodies were significantly decreased at L-10 (p virus. The 11 astronauts who showed evidence of EBV reactivation had significant increases in urinary epinephrine and norepinephrine as compared with astronauts without EBV reactivation. CONCLUSION: These findings indicate that physical and psychological stresses associated with spaceflight resulted in decreased virus-specific T-cell immunity and reactivation of EBV.

  17. Reactivation of Latent Epstein-Barr Virus; A Comparison After Gamma Rays and Proton Treatment

    Science.gov (United States)

    Mehta, Satish K.; Plante, Ianik; Bloom, David C.; Stowe, Raymond; Renner, Ashlie; Wu, Honglu; Crucian, Brian; Pierson, Duane L.

    2017-01-01

    Among different unique stressors astronauts are exposed to during spaceflight, cosmic radiation constitutes an important one that leads to various health effects. In particular, space radiation may contribute to decreased immunity, which has been observed in astronauts during short and long duration missions, as evidenced by several changes in cellular immunity and plasma cytokines levels. Reactivation of latent herpes viruses, either directly from radiation or resulting from perturbation in the immune system, is also observed in astronauts. While EBV is one of the eight human herpes viruses known to infect more than 90% human adults and stays latent for the life of the host without normally causing adverse effects of reactivation, increased reactivation in astronauts is well-documented, though the mechanism of this increase is not understood. In this work, we have studied the effect of two different types of radiations, Cs-137 gamma and 150-MeV proton on the reactivation rates of the Epstein - Barr virus (EBV) in vitro in EBV latent cell lines at doses of 0.1, 0.5, 1.0 and 2.0 Gy. While we find that both types of radiations reactivated latent EBV in vitro, we observe that at equivalent doses, early response is stronger for protons but with time, the reactivation induced by gamma rays is more persistent. These differences between the protons and gamma rays curves in latent virus reactivation challenge the common paradigm that protons and gamma rays have similar biological effects.

  18. Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1.

    Science.gov (United States)

    Esau, Daniel

    2017-01-01

    In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

  19. Human Complement Receptor Type 1/CD35 Is an Epstein-Barr Virus Receptor

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    Javier G. Ogembo

    2013-02-01

    Full Text Available Epstein-Barr virus (EBV attachment to primary B cells initiates virus entry. Although CD21 is the only known receptor for EBVgp350/220, a recent report documents EBV-infected B cells from a patient genetically deficient in CD21. On normal resting B cells, CD21 forms two membrane complexes: one with CD19 and another with CD35. Whereas the CD21/CD19 complex is widely retained on immortalized and B cell tumor lines, the related complement-regulatory protein CD35 is lost. To determine the role(s of CD35 in initial infection, we transduced a CD21-negative pre-B cell and myeloid leukemia line with CD35, CD21, or both. Cells expressing CD35 alone bound gp350/220 and became latently infected when the fusion receptor HLA II was coexpressed. Temporal, biophysical, and structural characteristics of CD35-mediated infection were distinct from CD21. Identification of CD35 as an EBV receptor uncovers a salient role in primary infection, addresses unsettled questions of virus tropism, and underscores the importance of EBVgp350/220 for vaccine development.

  20. Pathogenic Role of Exosomes in Epstein-Barr Virus (EBV)-Associated Cancers

    Science.gov (United States)

    Teow, Sin-Yeang; Liew, Kitson; Khoo, Alan Soo-Beng; Peh, Suat-Cheng

    2017-01-01

    Exosomes are 40- to 100-nm membrane-bound small vesicles that carry a great variety of cellular cargoes including proteins, DNA, messenger RNAs (mRNAs), and microRNAs (miRNAs). These nanovesicles are detected in various biological fluids such as serum, urine, saliva, and seminal fluids. Exosomes serve as key mediators in intercellular communication by facilitating the transfer and exchange of cellular components from cells to cells. They contain various pathogenic factors whereby their adverse effects have been implicated in multiple viral infections and cancers. Interestingly, accumulating evidences showed that exosomes derived from tumour viruses or oncoviruses, exacerbate virus-associated cancers by remodelling the tumour microenvironment. In this review, we summarize the contributing factors of Epstein-Barr virus (EBV) products-containing exosomes in viral pathogenesis and their potential implications in EBV-driven malignancies. Understanding the biological role of these exosomes in the disease would undoubtedly boost the development of a more comprehensive strategy to combat EBV-associated cancers and to better predict the therapeutic outcomes. Furthermore, we also highlight the potentials and challenges of EBV products-containing exosomes being employed as diagnostic markers and therapeutic targets for EBV-related cancers. Since these aspects are rather underexplored, we attempt to underline interesting areas that warrant further investigations in the future. PMID:29104494

  1. Infektion mit Epstein-Barr-Virus und Tumor-Entstehung beim Menschen

    Science.gov (United States)

    Kirchner, H.

    1981-08-01

    The Epstein-Barr Virus (EBV) is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated. These tumors are one type of nasopharyngeal carcinoma which is frequent in parts of East Asia and the Burkitt lymphoma which predominantly occurs in parts of Africa and New Guinea. Nonetheless, the EBV is the causative agent of infectious mononucleosis (IM), a benign, self-limiting lymphoproliferative disease of adolescents. The major difference between the countries in which the EBV-induced tumors occur and those in which IM occurs is the late primary EBV infection in the latter, whereas primary infection with EBV occurs in the first year of life in the former. All theories of viral carcinogenesis have to explain the long latency period between primary infection and tumor growth and how an ubiquitous virus may be oncogenic. Thus, invariably, one has to assume a role of cofactors, which may be of cytogenetic nature or may be represented by additional infections or by chemical agents. Since most modern theories of carcinogenesis consider a multi-step development of tumors, the theory that infection with an ubiquitous virus at the right time of life represents one step to carcinogenesis seems to be tenable.

  2. Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells.

    Science.gov (United States)

    Greijer, A E; Ramayanti, O; Verkuijlen, S A W M; Novalić, Z; Juwana, H; Middeldorp, J M

    2017-03-01

    Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts. These transcripts include (but are not restricted to), EBNA1, EBNA2, LMP1, LMP2, BARTs, EBER1, BARF1 and ZEBRA, Rta, BGLF4 (PK), BXLF1 (TK) and BFRF3 (VCAp18) all of which have been implicated in EBV-driven oncogenesis and viral replication. With this method we determine the amount of RNA copies per infected (tumor) cell in bulk populations of various origin. While we confirm the expected RNA profiles within classic EBV latency programs, this sensitive quantitative approach revealed the presence of rare cells undergoing lytic replication. Inducing lytic replication in EBV tumor cells supports apoptosis and is considered as therapeutic approach to treat EBV-driven malignancies. This sensitive multi-primed quantitative RT-PCR approach can provide broader understanding of transcriptional activity in latent and lytic EBV infection and is suitable for monitoring virus-specific therapy responses in patients with EBV associated cancers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Pathogenic Role of Exosomes in Epstein-Barr Virus (EBV)-Associated Cancers.

    Science.gov (United States)

    Teow, Sin-Yeang; Liew, Kitson; Khoo, Alan Soo-Beng; Peh, Suat-Cheng

    2017-01-01

    Exosomes are 40- to 100-nm membrane-bound small vesicles that carry a great variety of cellular cargoes including proteins, DNA, messenger RNAs (mRNAs), and microRNAs (miRNAs). These nanovesicles are detected in various biological fluids such as serum, urine, saliva, and seminal fluids. Exosomes serve as key mediators in intercellular communication by facilitating the transfer and exchange of cellular components from cells to cells. They contain various pathogenic factors whereby their adverse effects have been implicated in multiple viral infections and cancers. Interestingly, accumulating evidences showed that exosomes derived from tumour viruses or oncoviruses, exacerbate virus-associated cancers by remodelling the tumour microenvironment. In this review, we summarize the contributing factors of Epstein-Barr virus (EBV) products-containing exosomes in viral pathogenesis and their potential implications in EBV-driven malignancies. Understanding the biological role of these exosomes in the disease would undoubtedly boost the development of a more comprehensive strategy to combat EBV-associated cancers and to better predict the therapeutic outcomes. Furthermore, we also highlight the potentials and challenges of EBV products-containing exosomes being employed as diagnostic markers and therapeutic targets for EBV-related cancers. Since these aspects are rather underexplored, we attempt to underline interesting areas that warrant further investigations in the future.

  4. Epidemiology of Epstein-Barr virus-associated pediatric lymphomas from Argentina.

    Science.gov (United States)

    Chabay, Paola; Preciado, María Victoria

    More than 90% of the population is infected by Epstein-Barr virus (EBV), which has sophisticatedly evolved to survive silently in B cells for the life of infected individuals. However, if the virus-host balance is disturbed, latent EBV infection could be associated with several lymphomas. The age at primary infection varies substantially worldwide, and exposure to EBV is likely to be due to socioeconomic factors. In Argentina, EBV infection is mostly subclinical and 90% of patients are seropositive by the age of 3 years; therefore, its epidemiological characteristics resemble those of an underdeveloped or developing population. EBV-positive Hodgkin lymphoma (HL) in young adults from developed populations has been attributed to delayed primary EBV infection as suggested by the association with recent mononucleosis development. EBV-associated Burkitt lymphoma and Hodgkin lymphoma in children from Argentina display frequencies similar to those observed in developed countries, whereas EBV presence in pediatric diffuse large B-cell lymphoma is slightly increased compared to those populations. However, EBV presence is statistically associated particularly with patients < 10 years of age in all three entities. Therefore, a relationship between low age of EBV seroconversion and B-cell lymphoma development risk could be suggested in children from Argentina. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Gammaherpesvirus latency accentuates EAE pathogenesis: relevance to Epstein-Barr virus and multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Costanza Casiraghi

    Full Text Available Epstein-Barr virus (EBV has been identified as a putative environmental trigger of multiple sclerosis (MS, yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68, the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases.

  6. Azathioprine induced Epstein-Barr virus positive mucocutaneous ulcer: A case report

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    Arneja S

    2018-02-01

    Full Text Available Introduction: Epstein-Barr virus positive mucocutaneous ulcer (EBVMUC is a rare, newly described provisional entity in the 2016 Update of World Health Organization classification of lymphoid neoplasms. The histomorphological and immunophenotypical and molecular features overlap with classical Hodgkin’s lymphoma (cHL and can be mistaken for the same. Case report: A 70-year-old male, a known case of diabetes mellitus and hypertension, was diagnosed with Wegener’s granulomatosis (granulomatosis with polyangiitis in 2007. He was treated with prednisolone and cyclophosphamide, the latter drug was replaced with azathioprine in 2010. He was apparently well since then, until he presented in 2016 with an anal ulcer with a fistula tract formation, the ulcer on histomorphology and immunohistochemistry was diagnosed as EBVMUC. Discussion: EBVMUC was first described in patients with iatrogenic induced immunosuppression.They have later been found to be associated with various other causes of immunosuppression, like solid organ transplant recipients and human immunodeficiency virus (HIV, common factor in all these being immunosuppression. Conclusion: The importance of recognizing this entity lies in its morphological and immunophenotypic overlap with classical Hodgkin’s lymphoma (cHL and unlike latter, most often complete resolution of disease occurs with reduction of immunosuppressive dose. Therefore, correct recognition of the entity is essential to avoid overtreatment as lymphoma.

  7. Seroepidemiological Study of Epstein-Barr Virus in Different Population Groups in Croatia.

    Science.gov (United States)

    Beader, Nataša; Kolarić, Branko; Slačanac, Domagoj; Tabain, Irena; Vilibić-Čavlek, Tatjana

    2018-02-01

    The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population. To analyze the seroprevalence of EBV infection in different population groups in Croatia. During a 2 year period (2015-2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay. IgM/IgG-positive samples were further tested for IgG avidity. The overall prevalence of EBV IgG antibodies was 91.4%. Females had significantly higher IgG seroprevalence than males (93.1% vs. 89.9%, P = 0.008). According to age, IgG seropositivity increased progressively from 59.6% in children age 40. All IgM positive participants > 40 years showed high IgG avidity. Logistic regression showed that age is associated with EBV IgG seropositivity. EBV is widespread in the Croatian population. Older age appears to be the main risk factor for EBV seropositivity.

  8. Epidemiology of Epstein-Barr virus-associated pediatric lymphomas from Argentina

    Directory of Open Access Journals (Sweden)

    Paola Chabay

    2016-01-01

    Full Text Available More than 90% of the population is infected by Epstein-Barr virus (EBV, which has sophisticatedly evolved to survive silently in B cells for the life of infected individuals. However, if the virus-host balance is disturbed, latent EBV infection could be associated with several lymphomas. The age at primary infection varies substantially worldwide, and exposure to EBV is likely to be due to socioeconomic factors. In Argentina, EBV infection is mostly subclinical and 90% of patients are seropositive by the age of 3 years; therefore, its epidemiological characteristics resemble those of an underdeveloped or developing population. EBV-positive Hodgkin lymphoma (HL in young adults from developed populations has been attributed to delayed primary EBV infection as suggested by the association with recent mononucleosis development. EBV-associated Burkitt lymphoma and Hodgkin lymphoma in children from Argentina display frequencies similar to those observed in developed countries, whereas EBV presence in pediatric diffuse large B-cell lymphoma is slightly increased compared to those populations. However, EBV presence is statistically associated particularly with patients < 10 years of age in all three entities. Therefore, a relationship between low age of EBV seroconversion and B-cell lymphoma development risk could be suggested in children from Argentina.

  9. An update: Epstein-Barr virus and immune evasion via microRNA regulation.

    Science.gov (United States)

    Zuo, Lielian; Yue, Wenxin; Du, Shujuan; Xin, Shuyu; Zhang, Jing; Liu, Lingzhi; Li, Guiyuan; Lu, Jianhong

    2017-06-01

    Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans. To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs targeting both viral and host genes involved in the immune response. The miRNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4 + and CD8 + T cell response of infected cells. These reports strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host miRNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.

  10. Carcinoma-risk variant of EBNA1 deregulates Epstein-Barr Virus episomal latency.

    Science.gov (United States)

    Dheekollu, Jayaraju; Malecka, Kimberly; Wiedmer, Andreas; Delecluse, Henri-Jacques; Chiang, Alan K S; Altieri, Dario C; Messick, Troy E; Lieberman, Paul M

    2017-01-31

    Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection. We identify Survivin as a host protein deficiently bound by the NPC variant of EBNA1 and show that Survivin depletion compromises EBV episome maintenance in multiple cell types. We propose that endemic variants of EBNA1 play a significant role in EBV-driven carcinogenesis by altering key regulatory interactions that destabilize latent infection.

  11. Pathogenesis and FDG-PET/CT findings of Epstein-Barr virus-related lymphoid neoplasms.

    Science.gov (United States)

    Toriihara, Akira; Nakajima, Reiko; Arai, Ayako; Nakadate, Masashi; Abe, Koichiro; Kubota, Kazunori; Tateishi, Ukihide

    2017-07-01

    Epstein-Barr virus (EBV) is one of the most common viruses, infecting more than 90% of the adult population worldwide. EBV genome is detected in some lymphoid neoplasms. Not only their histopathological subtypes, but also their backgrounds and their clinical courses are variable. A number of B-cell lymphoproliferative disorders associated with the immunocompromised state are related to EBV infection. The incidences of these disorders have been increasing along with generalization of organ transplantations and use of immunosuppressive treatments. Furthermore, some EBV-positive lymphoma can also occur in immunocompetent patients. While evaluating patients with generalized lymphadenopathy of unknown cause by positron emission tomography/computed tomography with 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG-PET/CT), the possibility of lymphoid neoplasms should be considered in some patients, and a careful review of the background and previous history of the patients is necessary. In this review article, we describe the pathogenesis of EBV-related lymphoid neoplasms and then present FDG-PET/CT images of representative diseases. In addition, we also present a review of other EBV-related diseases, such as infectious mononucleosis and nasopharyngeal carcinoma.

  12. Stress-induced reactivation of Epstein-Barr virus in astronauts

    Science.gov (United States)

    Stowe, R. P.; Pierson, D. L.; Feeback, D. L.; Barrett, A. D.

    2000-01-01

    Herpesviruses are leading causes of infectious blindness and death in immunocompromised individuals. Impaired cellular immunity, which is known to result in increased frequency and severity of herpesvirus infections, has been demonstrated both during and after spaceflight. Therefore, we examined whether Epstein-Barr virus (EBV), a well-characterized latent herpesvirus, undergoes reactivation in astronauts. Sera from Shuttle astronauts, taken before and after spaceflight, were examined for evidence of EBV reactivation. The geometric mean antibody titer to EBV viral capsid antigen (VCA) was significantly increased prior to flight compared to baseline (p = 0. 0001). After spaceflight, evidence of acute lytic replication was found in which 8- to 64-fold increases in EBV early antigen (EA) antibodies occurred without significant increases in antibodies to measles virus. Additionally, stress-induced shifts in circulating leukocytes and elevated levels of urinary cortisol and epinephrine were found. Overall, significant increases in EA or high VCA/EA antibody titers were found in 8 of 23 (35%) male astronauts and 3 of 5 (60%) female astronauts. These results indicate that stress reactivates EBV prior to flight and suggest that acute lytic replication of EBV occurs during spaceflight. Copyright 2000 S. Karger AG, Basel.

  13. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners

    Science.gov (United States)

    Mehta, S. K.; Pierson, D. L.; Cooley, H.; Dubow, R.; Lugg, D.

    2000-01-01

    Epstein-Barr virus (EBV) reactivation and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at 2 Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity (DTH) skin testing was used as an indicator of the CMI response, that was evaluated 2 times before winter isolation and 3 times during isolation. At all 5 evaluation times, 8 or more of the 16 subjects had a diminished CMI response. Diminished DTH was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal DTH responses for all 5 tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, during, and after the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least 1 occasion. The probability of EBV shedding increased (P = 0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (P viruses.

  14. From Conventional to Next Generation Sequencing of Epstein-Barr Virus Genomes.

    Science.gov (United States)

    Kwok, Hin; Chiang, Alan Kwok Shing

    2016-02-24

    Genomic sequences of Epstein-Barr virus (EBV) have been of interest because the virus is associated with cancers, such as nasopharyngeal carcinoma, and conditions such as infectious mononucleosis. The progress of whole-genome EBV sequencing has been limited by the inefficiency and cost of the first-generation sequencing technology. With the advancement of next-generation sequencing (NGS) and target enrichment strategies, increasing number of EBV genomes has been published. These genomes were sequenced using different approaches, either with or without EBV DNA enrichment. This review provides an overview of the EBV genomes published to date, and a description of the sequencing technology and bioinformatic analyses employed in generating these sequences. We further explored ways through which the quality of sequencing data can be improved, such as using DNA oligos for capture hybridization, and longer insert size and read length in the sequencing runs. These advances will enable large-scale genomic sequencing of EBV which will facilitate a better understanding of the genetic variations of EBV in different geographic regions and discovery of potentially pathogenic variants in specific diseases.

  15. A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells.

    Science.gov (United States)

    Ersing, Ina; Nobre, Luis; Wang, Liang Wei; Soday, Lior; Ma, Yijie; Paulo, Joao A; Narita, Yohei; Ashbaugh, Camille W; Jiang, Chang; Grayson, Nicholas E; Kieff, Elliott; Gygi, Steven P; Weekes, Michael P; Gewurz, Benjamin E

    2017-05-16

    Epstein-Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced remodeling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma-associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. [Regulation and evasion of host immune responses by Epstein-Barr virus].

    Science.gov (United States)

    Xiao, Nanyang; Chen, Qi; Cai, Shaoli

    2016-01-04

    Epstein-Barr virus (EBV) is the first identified human oncogenic DNA virus in the gamma-herpesvirus family. EBV triggers a cascade events of innate immune responses through Toll-like receptor signaling including the production of type I interferons and the activation of functional autophagy. However, EBV has developed much more elaborate and sophisticated strategies for subverting and escaping the host immune system, such as limiting its own gene expression, activing the host ubiquitin-specific protease system, and interfering ubiquitin modification. EBV impairs the host immune system, leading to lifelong persistent infections, which in turn result in the occurrence of EBV-associated diseases, such as nasopharyngeal carcinoma and infectious mononucleosis. Thus, to better understand the mechanisms regarding the infection latentency and oncogenicity of EBV invasion will be crucial for identifying potential immunotherapeutic targets for EBV- related diseases, such as infectious mononucleosis and nasopharyngeal carcinoma. In this article, we discuss the research advances regarding the virology and immunology of EBV in the modulation of the host immune response and evasion.

  17. Characterization of skin blister fluids from children with Epstein-Barr virus-associated lymphoproliferative disease.

    Science.gov (United States)

    Wada, Taizo; Toma, Tomoko; Miyazawa, Hanae; Koizumi, Eiko; Shirahashi, Tetsujiro; Matsuda, Yusuke; Yachie, Akihiro

    2018-01-20

    Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids. © 2018 Japanese Dermatological Association.

  18. Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment

    Science.gov (United States)

    Yap, Hooi-Yeen; Peh, Suat-Cheng

    2017-01-01

    Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets B-lymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt's lymphoma (BL), and Hodgkin's lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development as well as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside. PMID:29464124

  19. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma

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    Chang, Ellen T.; Ambinder, Richard F.; Lennette, Evelyne T.; Rubertone, Mark V.; Mann, Risa B.; Borowitz, Michael; Weir, Edward G.; Abbondanzo, Susan L.; Mueller, Nancy E.

    2012-01-01

    An altered anti–Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV+ and EBV− Hodgkin lymphoma. Among 40 EBV+ Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti–EBNA-1/anti–EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV− Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV+ disease was significantly associated with a low anti–EBNA-1/anti–EBNA-2 antibody ratio. This distinc-tive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV+ but not EBV− Hodgkin lymphoma. PMID:22972983

  20. Frequency of Epstein-Barr virus DNA sequences in human gliomas

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    Renata Fragelli Fonseca

    Full Text Available CONTEXT AND OBJECTIVE: The Epstein-Barr virus (EBV is the most common cause of infectious mononucleosis and is also associated with several human tumors, including Burkitt's lymphoma, Hodgkin's lymphoma, some cases of gastric carcinoma and nasopharyngeal carcinoma, among other neoplasms. The aim of this study was to screen 75 primary gliomas for the presence of specific EBV DNA sequences by means of the polymerase chain reaction (PCR, with confirmation by direct sequencing. DESIGN AND SETTING: Prevalence study on EBV molecular genetics at a molecular pathology laboratory in a university hospital and at an applied genetics laboratory in a national institution. METHODS: A total of 75 primary glioma biopsies and 6 others from other tumors from the central nervous system were obtained. The tissues were immediately frozen for subsequent DNA extraction by means of traditional methods using proteinase K digestion and extraction with a phenol-chloroform-isoamyl alcohol mixture. DNA was precipitated with ethanol, resuspended in buffer and stored. The PCRs were carried out using primers for amplification of the EBV BamM region. Positive and negative controls were added to each reaction. The PCR products were used for direct sequencing for confirmation. RESULTS: The viral sequences were positive in 11/75 (14.7% of our samples. CONCLUSION: The prevalence of EBV DNA was 11/75 (14.7% in our glioma collection. Further molecular and epidemiological studies are needed to establish the possible role played by EBV in the tumorigenesis of gliomas.

  1. Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody exacerbated by epstein-barr virus.

    Science.gov (United States)

    Fadeyi, Emmanuel A; Simmons, Julie H; Jones, Mary Rose; Palavecino, Elizabeth L; Pomper, Gregory J

    2015-01-01

    Most cases of autoimmune hemolytic anemia (AIHA) are caused by the production of an autoantibody that targets determinants on red blood cells (RBCs). This autoantibody can be immunoglobulin (Ig) G, IgM, or IgA. Some autoantibodies react optimally at 0° to 4°C (ie, cold agglutinin) and usually are clinically insignificant. High-titer cold agglutinins are associated with IgM autoantibody and complement fixation induced by infectious agents, including the Epstein-Barr virus (EBV). This case report describes a 31-year-old man who had jaundice, a hemoglobin of 6.0 gdL, and was diagnosed with a hemolytic crisis of AIHA. He received a total of 11 RBC transfusions during a 15-hour period without sustained response and later died. The direct antiglobulin test results for this patient were positive, whereas the cold-agglutinin-testing results were negative. We detected EBV DNA in blood via polymerase chain reaction (PCR). We report a rare case of AIHA associated with an IgG autoantibody and exacerbated by EBV infection, causing a fatal hemolytic anemia. Copyright© by the American Society for Clinical Pathology (ASCP).

  2. Status of Epstein-Barr Virus Coinfection with Helicobacter pylori in Gastric Cancer

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    Singh, Shyam

    2017-01-01

    Epstein-Barr virus is a ubiquitous human herpesvirus whose primary infection causes mononucleosis, Burkett's lymphoma, nasopharyngeal carcinoma, autoimmune diseases, and gastric cancer (GC). The persistent infection causes malignancies in lymph and epithelial cells. Helicobacter pylori causes gastritis in human with chronic inflammation. This chronic inflammation is thought to be the cause of genomic instability. About 45%-word population have a probability of having both pathogens, namely, H. pylori and EBV. Approximately 180 per hundred thousand population is developing GC along with many gastric abnormalities. This makes GC the third leading cause of cancer-related death worldwide. Although lots of research are carried out individually for EBV and H. pylori, still there are very few reports available on coinfection of both pathogens. Recent studies suggested that EBV and H. pylori coinfection increases the occurrence of GC as well as the early age of GC detection comparing to individual infection. The aim of this review is to present status on coinfection of both pathogens and their association with GC. PMID:28421114

  3. Epstein-Barr Virus-related post-transplant lymphoproliferative disorders: pathogenetic insights for targeted therapy.

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    Nourse, J P; Jones, K; Gandhi, M K

    2011-05-01

    Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of major, life-threatening lymphoproliferative diseases occurring in the post-transplant setting. The majority of PTLD is of B-cell origin and is associated with several risk factors, the most significant being Epstein-Barr virus (EBV) infection. EBV's in vitro transforming abilities, distinctive latency, clonality within the malignant cells and response to targeted therapies implicate a critical role in the biology of PTLD. This minireview focuses on EBV-related PTLD pathogenesis, in particular the interplay between aspects of the EBV life cycle and latency with nonviral factors resulting in the wide spectrum of histology and clinical presentations encountered in PTLD. With the increased prevalence of transplantation a rise in the incidence of PTLD may be expected. Therefore the importance of laboratory and animal models in the understanding of PTLD and the development of novel therapeutic approaches is discussed. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

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    Iwakiri, Dai [Institute for Genetic Medicine, Hokkaido University, N15 W7 Kita-Ku, Sapporo 060-0815 (Japan)

    2014-08-06

    The Epstein-Barr virus (EBV) is known as an oncogenic herpesvirus that has been implicated in the pathogenesis of various malignancies. EBV-encoded RNAs (EBERs) are non-coding RNAs expressed abundantly in latently EBV-infected cells. Herein, I summarize the current understanding of the functions of EBERs, including the interactions with cellular factors through which EBERs contribute to EBV-mediated pathogenesis. Previous studies have demonstrated that EBERs are responsible for malignant phenotypes in lymphoid cells, and can induce several cytokines that can promote the growth of various EBV-infected cancer cells. EBERs were also found to bind retinoic acid-inducible gene I (RIG-I) and thus activate its downstream signaling. Furthermore, EBERs induce interleukin-10, an autocrine growth factor for Burkitt’s lymphoma cells, by activating RIG-I/interferon regulatory factor 3 pathway, suggesting that EBER-mediated innate immune signaling modulation contributes to EBV-mediated oncogenesis. Recently, EBV-infected cells were reported to secret EBERs, which were then recognized by toll-like receptor 3 (TLR3), leading to the induction of type I interferon and inflammatory cytokines, and subsequent immune activation. Furthermore, EBER1 was detected in the sera of patients with active EBV-infectious diseases, suggesting that EBER1-meidated TLR3 signaling activation could account for the pathogenesis of active EBV-infectious diseases.

  5. Emerging Roles of Small Epstein-Barr Virus Derived Non-Coding RNAs in Epithelial Malignancy

    Directory of Open Access Journals (Sweden)

    Ka-Fai To

    2013-08-01

    Full Text Available Latent Epstein-Barr virus (EBV infection is an etiological factor in the progression of several human epithelial malignancies such as nasopharyngeal carcinoma (NPC and a subset of gastric carcinoma. Reports have shown that EBV produces several viral oncoproteins, yet their pathological roles in carcinogenesis are not fully elucidated. Studies on the recently discovered of EBV-encoded microRNAs (ebv-miRNAs showed that these small molecules function as post-transcriptional gene regulators and may play a role in the carcinogenesis process. In NPC and EBV positive gastric carcinoma (EBVaGC, 22 viral miRNAs which are located in the long alternative splicing EBV transcripts, named BamH1 A rightward transcripts (BARTs, are abundantly expressed. The importance of several miR-BARTs in carcinogenesis has recently been demonstrated. These novel findings enhance our understanding of the oncogenic properties of EBV and may lead to a more effective design of therapeutic regimens to combat EBV-associated malignancies. This article will review the pathological roles of miR-BARTs in modulating the expression of cancer-related genes in both host and viral genomes. The expression of other small non-coding RNAs in NPC and the expression pattern of miR-BARTs in rare EBV-associated epithelial cancers will also be discussed.

  6. Epstein-Barr Virus Type 2 Infects T Cells in Healthy Kenyan Children.

    Science.gov (United States)

    Coleman, Carrie B; Daud, Ibrahim I; Ogolla, Sidney O; Ritchie, Julie A; Smith, Nicholas A; Sumba, Peter O; Dent, Arlene E; Rochford, Rosemary

    2017-09-15

    The 2 strains of Epstein-Barr virus (EBV), EBV type 1 (EBV-1) and EBV-2, differ in latency genes, suggesting that they use distinct mechanisms to establish latency. We previously reported that EBV-2 infects T cells in vitro. In this study, we tested the possibility that EBV-2 infects T cells in vivo. Purified T-cell fractions isolated from children positive for EBV-1 or EBV-2 and their mothers were examined for the presence of EBV and for EBV type. We detected EBV-2 in all T-cell samples obtained from EBV-2-infected children at 12 months of age, with some children retaining EBV-2-positive T cells through 24 months of age, suggesting that EBV-2 persists in T cells. We were unable to detect EBV-2 in T-cell samples from mothers but could detect EBV-2 in samples of their breast milk and saliva. These data suggest that EBV-2 uses T cells as an additional latency reservoir but that, over time, the frequency of infected T cells may drop below detectable levels. Alternatively, EBV-2 may establish a prolonged transient infection in the T-cell compartment. Collectively, these novel findings demonstrate that EBV-2 infects T cells in vivo and suggest EBV-2 may use the T-cell compartment to establish latency. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. Plasticity of DNA replication initiation in Epstein-Barr virus episomes.

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    Paolo Norio

    2004-06-01

    Full Text Available In mammalian cells, the activity of the sites of initiation of DNA replication appears to be influenced epigenetically, but this regulation is not fully understood. Most studies of DNA replication have focused on the activity of individual initiation sites, making it difficult to evaluate the impact of changes in initiation activity on the replication of entire genomic loci. Here, we used single molecule analysis of replicated DNA (SMARD to study the latent duplication of Epstein-Barr virus (EBV episomes in human cell lines. We found that initiation sites are present throughout the EBV genome and that their utilization is not conserved in different EBV strains. In addition, SMARD shows that modifications in the utilization of multiple initiation sites occur across large genomic regions (tens of kilobases in size. These observations indicate that individual initiation sites play a limited role in determining the replication dynamics of the EBV genome. Long-range mechanisms and the genomic context appear to play much more important roles, affecting the frequency of utilization and the order of activation of multiple initiation sites. Finally, these results confirm that initiation sites are extremely redundant elements of the EBV genome. We propose that these conclusions also apply to mammalian chromosomes.

  8. Malaria, Epstein-Barr virus infection and the pathogenesis of Burkitt's lymphoma.

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    Mawson, Anthony R; Majumdar, Suvankar

    2017-11-01

    A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR, Path Global Health 2013;107(3):122-9). Repeated episodes of malaria would therefore be expected to expose the tissues of affected individuals to potentially toxic doses of vitamin A. It is proposed that such episodes activate latent EBV infection, which in turn activates retinoid-responsive genes. Expression of these genes enhances viral replication and induces germinal center (GC) B cell expansion, activation-induced cytidine deaminase (AID) expression, and c-myc translocation, which in turn predisposes to BL. Thus, an endogenous form of retinoid toxicity related to malaria infection may be the common factor linking frequent malaria, EBV infection and BL, whereby prolonged exposure of lymphatic tissues to high concentrations of retinoids may combine to induce B-cell translocation and increase the risk of Burkitt's lymphoma. © 2017 UICC.

  9. Epstein Barr virus-positive mucocutaneous ulcer of the colon associated Hodgkin lymphoma in Crohn's disease.

    Science.gov (United States)

    Moran, Neil R; Webster, Bradley; Lee, Kenneth M; Trotman, Judith; Kwan, Yiu-Lam; Napoli, John; Leong, Rupert W

    2015-05-21

    Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn's disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn's disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease.

  10. Characterization of Epstein Barr virus latency pattern in Argentine breast carcinoma.

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    Mario A Lorenzetti

    Full Text Available INTRODUCTION: Epstein-Barr virus (EBV-associated tumors show different expression patterns of latency genes. Since in breast carcinoma this pattern is not yet fully described, our aim was to characterize EBV latency pattern in our EBV positive breast carcinoma series. METHODS: The study was conducted on 71 biopsies of breast carcinoma and in 48 non-neoplastic breast controls. EBNA1, LMP2A and LMP1 expression was assessed by immunohistochemistry with monoclonal antibodies, while viral genomic DNA and EBERs RNA transcripts expression was performed by in situ hybridization. EBV presence was confirmed by PCR. RESULTS: EBV genomic DNA and EBNA1 expression were detected in 31% (22/71 of patients specifically restricted to tumor epithelial cells in breast carcinoma while all breast control samples were negative for both viral DNA and EBNA1 protein. LMP2A was detected in 73% of EBNA1 positive cases, none of which expressed either LMP1 protein or EBERs transcripts. CONCLUSIONS: These findings suggest that EBV expression pattern in the studied biopsies could be different from those previously observed in breast carcinoma cell lines and lead us to suggest a new, EBNA1, LMP2A positive and LMP1 and EBERs negative latency profile in breast carcinoma in our population.

  11. Characterization of Epstein Barr virus latency pattern in Argentine breast carcinoma.

    Science.gov (United States)

    Lorenzetti, Mario A; De Matteo, Elena; Gass, Hugo; Martinez Vazquez, Paula; Lara, Julia; Gonzalez, Pedro; Preciado, María Victoria; Chabay, Paola A

    2010-10-22

    Epstein-Barr virus (EBV)-associated tumors show different expression patterns of latency genes. Since in breast carcinoma this pattern is not yet fully described, our aim was to characterize EBV latency pattern in our EBV positive breast carcinoma series. The study was conducted on 71 biopsies of breast carcinoma and in 48 non-neoplastic breast controls. EBNA1, LMP2A and LMP1 expression was assessed by immunohistochemistry with monoclonal antibodies, while viral genomic DNA and EBERs RNA transcripts expression was performed by in situ hybridization. EBV presence was confirmed by PCR. EBV genomic DNA and EBNA1 expression were detected in 31% (22/71) of patients specifically restricted to tumor epithelial cells in breast carcinoma while all breast control samples were negative for both viral DNA and EBNA1 protein. LMP2A was detected in 73% of EBNA1 positive cases, none of which expressed either LMP1 protein or EBERs transcripts. These findings suggest that EBV expression pattern in the studied biopsies could be different from those previously observed in breast carcinoma cell lines and lead us to suggest a new, EBNA1, LMP2A positive and LMP1 and EBERs negative latency profile in breast carcinoma in our population.

  12. Detection of Epstein-Barr and Human Papilloma Viruses in the Middle Ear Squamous Cell Carcinoma.

    Science.gov (United States)

    Surono, Agus; Hariwiyanto, Bambang; Samodra, Edhie

    2018-03-01

    The uncommon ear tumor of middle ear squamous cell carcinoma (MESCC) is thought to be associated with the history of long-term chronic otitis media in the most cases. The main etiologic factor of MESCC is still unclear and may be multifactorial. Infections of Epstein-Barr virus (EBV) and Human Papillomavirus (HPV) are considered as one of the etiologic factor of MESCC. Previous studies have shown that the EBV and HPV have been detected in MESCC. Although the EBV and HPV have been implicated in human malignancies, their roles in pathogenesis of MESCC have not been elucidated. There has never been report on the presence of EBV and HPV in Indonesian MESCC. This study aimed to determine the presence of EBV and HPV in MESCC. Seven paraffin-embedded tissues of speciment from biopsy were analyzed for the presence of EBV and HPV by immunohistochemistry, stained using polyclonal antibody anti EBNA1 and anti HPV. The samples consisted of 4 (57 %) males and 3 (43 %) females with age range of 26-87 years old. Immunohistochemistry result demonstrated that EBV was detected in three of seven (43 %) and HPV in two of seven (29 %) samples. Coexistence of the presence of EBV and HPV were found in one of seven (14 %) sample. The presence of EBV and HPV in MESCC suggests that viral infection may play an important etiologic role in the carcinogenesis of middle ear.

  13. Combinatorial epigenetic deregulation by Helicobacter pylori and Epstein-Barr virus infections in gastric tumourigenesis.

    Science.gov (United States)

    Wu, William Kk; Yu, Jun; Chan, Matthew Tv; To, Ka F; Cheng, Alfred Sl

    2016-07-01

    Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling and microRNAs, convert environmental signals to transcriptional outputs but are commonly hijacked by pathogenic microorganisms. Recent advances in cancer epigenomics have shed new light on the importance of epigenetic deregulation in Helicobacter pylori- and Epstein-Barr virus (EBV)-driven gastric tumourigenesis. Moreover, it is becoming apparent that epigenetic mechanisms interact through crosstalk and feedback loops, which modify global gene expression patterns. The SWI/SNF remodelling complexes are commonly involved in gastric cancers associated with H. pylori or EBV through different mechanisms, including microRNA-mediated deregulation and genetic mutations. While H. pylori causes epigenetic silencing of tumour-suppressor genes to deregulate cellular pathways, EBV-positive tumours exhibit a widespread and distinctive DNA hypermethylation profile. Given the early successes of epigenetic drugs in haematological malignancies, further studies are mandated to enrich and translate our understanding of combinatorial epigenetic deregulation in gastric cancers into interventional strategies in the clinic. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

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    Klein, George, E-mail: Georg.Klein@ki.se [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden); Klein, Eva; Kashuba, Elena [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden)

    2010-05-21

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  15. No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with Breast Cancer in Mexican Women

    Science.gov (United States)

    Morales-Sánchez, Abigail; Molina-Muñoz, Tzindilú; Martínez-López, Juan L. E.; Hernández-Sancén, Paulina; Mantilla, Alejandra; Leal, Yelda A.; Torres, Javier; Fuentes-Pananá, Ezequiel M.

    2013-10-01

    Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer.

  16. Primary meningeal Epstein-Barr virus-related leiomyosarcoma in a man infected with human immunodeficiency virus: review of literature, emphasizing the differential diagnosis and pathogenesis.

    Science.gov (United States)

    Zevallos-Giampietri, Eduardo-Alfredo; Yañes, Hugo Heinicke; Orrego Puelles, José; Barrionuevo, Carlos

    2004-12-01

    We describe the clinical, radiologic, surgical, and pathologic findings of a 29-year-old Peruvian human immunodeficiency virus-infected man with a primary parasellar meningeal leiomyosarcoma involving the left lesser esphenoidal wing and the cavernous sinus. Over a period of 13 months, he developed headache, vomiting, insomnia, and diplopia. Magnetic resonance imaging revealed a left parasellar extra-axial mass that was isointense in T1, hypointense in T2, and gadolinium-enhanced. The patient underwent subtotal resection of the tumor. The neoplasm was composed of spindle cells with smooth-muscle features. It showed moderate atypia, inconspicuous nucleoli, and scanty mitosis. No tumor necrosis was detected. The immunohistochemistry revealed strong positivity for vimentin, desmin, and smooth-muscle alpha-actin. A low-grade leiomyosarcoma was diagnosed. The in situ hybridization showed positive nuclear reactivity for Epstein-Barr virus-encoded RNA. The immunohistochemistry was negative for Epstein-Barr virus latent membrane protein 1. The main differential diagnosis of primary meningeal smooth-muscle tumors includes meningioma and peripheral nerve sheath tumors. Epstein-Barr virus has been demonstrated in most smooth-muscle tumors associated with acquired immune deficiency syndrome (AIDS). Primary meningeal smooth-muscle tumors, exceedingly rare neoplasms, remarkably affect young adults with AIDS. Comparatively, most AIDS-related visceral (nonmeningeal) smooth-muscle tumors have been reported in children. The permissiveness and tumorigenesis associated with Epstein-Barr virus may depend on the age of human immunodeficiency virus infection.

  17. CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells.

    Science.gov (United States)

    Yuen, Kit-San; Chan, Chi-Ping; Wong, Nok-Hei Mickey; Ho, Chau-Ha; Ho, Ting-Hin; Lei, Ting; Deng, Wen; Tsao, Sai Wah; Chen, Honglin; Kok, Kin-Hang; Jin, Dong-Yan

    2015-03-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a highly efficient and powerful tool for RNA-guided editing of the cellular genome. Whether CRISPR/Cas9 can also cleave the genome of DNA viruses such as Epstein-Barr virus (EBV), which undergo episomal replication in human cells, remains to be established. Here, we reported on CRISPR/Cas9-mediated editing of the EBV genome in human cells. Two guide RNAs (gRNAs) were used to direct a targeted deletion of 558 bp in the promoter region of BART (BamHI A rightward transcript) which encodes viral microRNAs (miRNAs). Targeted editing was achieved in several human epithelial cell lines latently infected with EBV, including nasopharyngeal carcinoma C666-1 cells. CRISPR/Cas9-mediated editing of the EBV genome was efficient. A recombinant virus with the desired deletion was obtained after puromycin selection of cells expressing Cas9 and gRNAs. No off-target cleavage was found by deep sequencing. The loss of BART miRNA expression and activity was verified, supporting the BART promoter as the major promoter of BART RNA. Although CRISPR/Cas9-mediated editing of the multicopy episome of EBV in infected HEK293 cells was mostly incomplete, viruses could be recovered and introduced into other cells at low m.o.i. Recombinant viruses with an edited genome could be further isolated through single-cell sorting. Finally, a DsRed selectable marker was successfully introduced into the EBV genome during the course of CRISPR/Cas9-mediated editing. Taken together, our work provided not only the first genetic evidence that the BART promoter drives the expression of the BART transcript, but also a new and efficient method for targeted editing of EBV genome in human cells. © 2015 The Authors.

  18. Inhibitory activities of microalgal extracts against Epstein-Barr Virus (EBV antigen expression in lymphoblastoid cells

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    Koh Yih Yih

    2014-01-01

    Full Text Available The inhibitory activities of microalgal extracts against the expression of three EBV antigens, latent membrane protein (LMP1, Epstein-Barr nuclear antigen (EBNA1 and Z Epstein-Barr reactivation activator (ZEBRA were assessed by immunocytochemistry. The observation that the methanol extracts and their fractions from Ankistrodesmus convolutus, Synechococcus elongatus and Spirulina platensis exhibited inhibitory activity against EBV proteins in three Burkitt’s lymphoma cell lines at concentrations as low as 20 μg/ml suggests that microalgae could be a potential source of antiviral compounds against EBV.

  19. Viral and bacterial aetiologies of male urethritis: findings of a high prevalence of Epstein-Barr virus.

    Science.gov (United States)

    Berntsson, M; Löwhagen, G-B; Bergström, T; Dubicanac, L; Welinder-Olsson, C; Alvengren, G; Tunbäck, P

    2010-03-01

    Male urethritis is one of the most common sexually transmitted infections (STIs). However, the aetiology is still unclear in many cases. In this study the prevalences of Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1), HSV-2, cytomegalovirus (CMV), adenovirus, Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum (including subtyping) were investigated. Samples from 112 male STI attendants with microscopically verified urethritis and from a control group of 103 men without clinical or microscopic signs of urethritis were analysed. Prevalences in the urethritis group compared with the controls were as follows: EBV 21%, 6% (P urethritis and may play a role in its pathogenesis.

  20. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

    Science.gov (United States)

    Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

    2016-12-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

  1. Presencia del virus de Epstein-Barr en casos colombianos de linfoma de Hodgkin y su relación con la respuesta al tratamiento.

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    Sandra Quijano

    2004-06-01

    Full Text Available En el desarrollo y patogénesis del linfoma de Hodgkin se ha propuesto al virus de Epstein-Barr como posible factor etiológico debido a la detección de ADN viral en las células de Reed- Sternberg en un subgrupo de tumores y a los altos niveles de expresión de la proteína latente de membrana 1 (LMP-1. El objetivo de este estudio fue determinar la presencia de virus de Epstein-Barr en 67 ganglios linfáticos de pacientes con diagnóstico confirmado de linfoma de Hodgkin mediante hibridación in situ para la detección de transcritos de ARN del virus de Epstein-Barr e inmunohistoquímica para la detección de la proteína oncogénica LMP-1. La presencia del virus se relacionó con el subtipo histológico, la respuesta al tratamiento de los pacientes y el fenotipo del infiltrado linfocitario. En el 67% de los casos se detectaron transcritos de virus de Epstein-Barr, la proteína LMP-1 se detectó en 56,7% de los casos en la célula tumoral de Reed-Sternberg. La presencia del virus en cada tipo histológico fue de 69,81% en esclerosis nodular, 85,71% en celularidad mixta y 40% en clásico. El virus de Epstein-Barr se detectó con mayor frecuencia en niños (84,2% en comparación con los adultos (60,4% y los pacientes positivos para el virus mostraron mejor respuesta al tratamiento, reflejada en una menor tendencia a presentar recaídas. El análisis del infiltrado mostró un predominio de linfocitos T CD4 y presencia de linfocitos T CD8, con mayor expresión de ambas subpoblaciones en casos positivos para virus de Epstein-Barr. Los resultados muestran un alto porcentaje de infección por virus de Epstein-Barr con una probable implicación significativa en la respuesta al tratamiento, lo que sugiere que la detección de virus de Epstein-Barr se podría usar como marcador de pronóstico en este tipo de linfoma.

  2. Epstein-Barr virus negative primary hepatic leiomyoma: Case report and literature review

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    Luo, Xian-Zhang; Ming, Chang-Sheng; Chen, Xiao-Ping; Gong, Nian-Qiao

    2013-01-01

    Primary hepatic leiomyoma is a neoplasm of mesenchymal origin and occurs only rarely. Secondary to benign smooth muscle proliferation, it is usually found in adult women and is associated with Epstein-Barr virus (EBV) infection. Here, we report the 29th case of primary hepatic leiomyoma with its unique features related to diagnosis, treatment and developmental biology. A 48-year-old man, with an immunocompromised status, complained of pain in the upper quadrant of the abdomen. Serological analysis indicated no presence of hepatitis virus, no human immunodeficiency virus, and no EBV infection. The levels of α-fetoprotein and carcinoembryonic antigen were normal. A mass was detected in segment III of the hepatic lobe by ultrasonography and an abdominal computed tomography scan. Endoscopy had negative findings. Exploratory laparotomy found no existing extrahepatic tumor and left lateral lobectomy was performed. Pathological examination showed the mass to be a typical leiomyoma. The cells were positive for α-smooth muscle actin and desmin, and negative for the makers of gastrointestinal stromal tumor (GIST), including CD117, CD34 and DOG1 (discovered on GIST1). In situ hybridization revealed negative status for EBV-encoded small RNA. After left lateral lobectomy, the patient was not given chemotherapy or radiotherapy. During a 2-year follow-up, no sign of local recurrence or distant metastasis was observed. In conclusion, we report a rare case of primary hepatic leiomyoma in a male patient without EBV infection. Hepatic resection was curative. This case presents data to expand our knowledge concerning the complex and heterogeneous nature of primary liver leiomyoma, indicating that EBV infection is important but neither necessary nor sufficient for the development of primary liver leiomyoma. PMID:23840159

  3. The prevalence of Epstein-Barr virus infection in head and neck non-Hodgkin's lymphomas in Khorasan, northeast of Iran

    International Nuclear Information System (INIS)

    Abadi, R.Z.M.; Mohtasham, N.; Veezi, T.; Pazouki, M.

    2013-01-01

    Objectives: To investigate the frequency and possible role of Epstein-Barr virus infection in non-Hodgkin's lymphomas of the oral cavity and maxillofacial region in Khorasan (Northeast of Iran). Methods: The cross-sectional retrospective study assessed the frequency of Epstein-Barr virus infection in non-immunosuppressed non-Hodgkin's lymphoma cases of the oral cavity and maxillofacial region. Formalin-fixed, paraffin-embedded tissue sections from 34 cases of head and neck non-Hodgkin's lymphoma (17 low-grade B-cell lymphoma, 14 diffuse large B-cell lymphoma, and 3 peripheral T cell lymphoma) were selected as a case group, and 10 normal lymph node sections were considered as a control group. Polymerase chain reaction was used to detect the EBV-DNA in tissue specimens. SPSS 16 was used for statistical analysis of the data. Results: EBV-DNA was detected in 26.5% of NHL samples. Among NHLs, Epstein-Barr virus was found to be positive in 50% cases with diffuse large B-cell lymphoma and 11.8% of low grade B-cell lymphomas. Epstein-Barr virus was not detected in any cases of peripheral T-cell lymphoma. Conclusion: Although it seems that Epstein-Barr virus appears to be an etiological factor in some subtypes of non-Hodgkin's lymphomas, especially in diffuse large B-cell lymphoma, more researches should be done to investigate the relationship between Epstein-Barr virus infection and head and neck non-Hodgkin's lymphomas. (author)

  4. Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases.

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    Abbott, Rachel J; Pachnio, Annette; Pedroza-Pacheco, Isabela; Leese, Alison M; Begum, Jusnara; Long, Heather M; Croom-Carter, Debbie; Stacey, Andrea; Moss, Paul A H; Hislop, Andrew D; Borrow, Persephone; Rickinson, Alan B; Bell, Andrew I

    2017-11-01

    Epstein-Barr virus (EBV) is typically acquired asymptomatically in childhood. In contrast, infection later in life often leads to infectious mononucleosis (IM), a febrile illness characterized by anti-EBV IgM antibody positivity, high loads of circulating latently infected B cells, and a marked lymphocytosis caused by hyperexpansion of EBV-specific CD8 + T cells plus a milder expansion of CD56 dim NKG2A + KIR - natural killer (NK) cells. How the two situations compare is unclear due to the paucity of studies on clinically silent infection. Here we describe five prospectively studied patients with asymptomatic infections identified in a seroepidemiologic survey of university entrants. In each case, the key blood sample had high cell-associated viral loads without a marked CD8 lymphocytosis or NK cell disturbance like those seen in patients during the acute phase of IM. Two of the cases with the highest viral loads showed a coincident expansion of activated EBV-specific CD8 + T cells, but overall CD8 + T cell numbers were either unaffected or only mildly increased. Two cases with slightly lower loads, in whom serology suggests the infection may have been caught earlier in the course of infection, also showed no T or NK cell expansion at the time. Interestingly, in another case with a higher viral load, in which T and NK cell responses were undetectable in the primary blood sample in which infection was detected, EBV-specific T cell responses did not appear until several months later, by which time the viral loads in the blood had already fallen. Thus, some patients with asymptomatic primary infections have very high circulating viral loads similar to those in patients during the acute phase of IM and a cell-mediated immune response that is qualitatively similar to that in IM patients but of a lower magnitude. However, other patients may have quite different immune responses that ultimately could reveal novel mechanisms of host control. IMPORTANCE Epstein-Barr virus

  5. Disseminated intravascular coagulation as an unusual presentation of an Epstein-Barr virus infection

    NARCIS (Netherlands)

    van Steijn, JHM; van Tol, KM; van Essen, LH; Gans, ROB

    2000-01-01

    Epstein-Barr viral (EBV)-infection usually presents as fever, sore throat, fatigue, lymphadenopathy and atypical lymphocytosis. We describe a patient with disseminated intravascular coagulation as the presenting symptom caused by a primary EBV infection. (C) 2000 Elsevier Science B.V. All rights

  6. Comparison of Epstein Barr Virus Antibodies And Tcell Cytokines Production in Patients With Multiple Sclerosis and Healthy Individuals

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    Amir Hassan Zarnani

    2010-11-01

    Full Text Available Background:Multiple sclerosis(MS is the most common autoimmune disease of central nervous system with destruction of myelin sheath mediated by auto reactive CD4+ T Lymphocytes. Because of the possible role of Epstein-Barr virus in etiology of MS and T cells immune response, the aim of this study was to evaluate anti-Epstein Barr virus antibodies as a marker of reactivity and production of TH1 and TH2 cytokines in MS patients and healthy individuals.   Methods: Blood samples were taken from 68 MS patients at different stages of diseases and 20 apparently healthy individuals and plasma levels of anti- EBV nuclear antigen-1 (EBNA-1 and viral capsid antigen (VCA antibodies determined and concentrations of IFN- [1] , IL-12 and IL-4 in culture supernatants of PHA-activated peripheral blood mononuclear cells (PBMC were measured by ELISA.   Results: The mean levels of anti EBNA-1 and VCAantibodies were significantly higher in patients compared to controls (p=0.04, p=0.001 respectively. Concentrations of IFN- [1] , IL-4 & IL-12 were also significantly higher in MS patients than healthy individuals (p=0.001, p=0.005, p=0.002, respectively. Significant correlation was found between anti EBNA-1 and VCAantibodies and IL-12 production (p =0.02, r=0.27& p=0.04, r=0.25, respectively; whereas no significant correlation was found between these antibodies and production of IFN- [1] or IL-4.   Conclusions: Due to elevated level of anti-EBV antibodies and T cell Cytokines in MS patients Rather than healthy individuals, Epstein Barr virus may play role in etiology of MS disease through activation of T cells immune response.

  7. Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding.

    Science.gov (United States)

    Sanosyan, Armen; Rutagwera, David G; Molès, Jean-Pierre; Bollore, Karine; Peries, Marianne; Kankasa, Chipepo; Mwiya, Mwiya; Tylleskär, Thorkild; Nagot, Nicolas; Van De Perre, Philippe; Tuaillon, Edouard

    2016-07-01

    Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.

  8. The role of cytomegalovirus, Haemophilus influenzae and Epstein Barr virus in Guillain Barre syndrome.

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    Shahriar Nafissi

    2013-06-01

    Full Text Available Guillain Barre Syndrome (GBS is an inflammatory, usually demyelinating, polyneuropathy; clinically characterized by acute onset of symmetric progressive muscle weakness with loss of myotatic reflexes. Thirty five patients with GBS, defined clinically according to the criteria of Asbury and Cornblath, were recruited from three hospital affiliated to Tehran University of Medical Sciences.As a control group 35 age and sex matched patients with other neurological diseases admitted to the same hospital at the same time, were included in our study. Serum samples were collected before treatment from each patient (within 4 weeks after the disease onset and controls, and stored frozen at -80ºC until serologic assays were done. Serologic testing of pretreatment serum was performed in all patients. Positive titer of virus specific IgM antibody against cytomegalovirus (CMV was found in 6 cases and 2 controls. 34 patients and 31 controls had high titer of anti Haemophilus influenzae IgG and one patient had serologic evidence of a recent Epstein Barr virus (EBV infection. The mean titer of IgG antibody against Haemophilus influenzae in cases and controls was 5.21 and 2.97 respectively. Although serologic evidence of all these infections were more frequent in cases than in controls, only Haemophilus influenzae infection appeared to be significantly related to GBS (P=0.002. Eleven cases and 3 controls had high titers of IgG antibody against Haemophilus influenzae type B (titer >8. There is significant association between high titer of IgG antibody against Haemophilus influenzae and GBS (P=0.017. Our results provide further evidence that Haemophilus influenzae and probably CMV, can be associated with GBS.

  9. Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections.

    Science.gov (United States)

    DeVoe, P W; Buckley, R H; Shirley, L R; Darby, C P; Ward, F E; Mickey, G H; Raab-Traub, N; Vandenbark, G R

    1985-01-01

    Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.

  10. Telomerase Activity Impacts on Epstein-Barr Virus Infection of AGS Cells

    Science.gov (United States)

    Rac, Jürgen; Haas, Florian; Schumacher, Andrina; Middeldorp, Jaap M.; Delecluse, Henri-Jacques; Speck, Roberto F.

    2015-01-01

    The Epstein-Barr virus (EBV) is transmitted from host-to-host via saliva and is associated with epithelial malignancies including nasopharyngeal carcinoma (NPC) and some forms of gastric carcinoma (GC). Nevertheless, EBV does not transform epithelial cells in vitro where it is rapidly lost from infected primary epithelial cells or epithelial tumor cells. Long-term infection by EBV, however, can be established in hTERT-immortalized nasopharyngeal epithelial cells. Here, we hypothesized that increased telomerase activity in epithelial cells enhances their susceptibility to infection by EBV. Using HONE-1, AGS and HEK293 cells we generated epithelial model cell lines with increased or suppressed telomerase activity by stable ectopic expression of hTERT or of a catalytically inactive, dominant negative hTERT mutant. Infection experiments with recombinant prototypic EBV (rB95.8), recombinant NPC EBV (rM81) with increased epithelial cell tropism compared to B95.8, or recombinant B95.8 EBV with BZLF1-knockout that is not able to undergo lytic replication, revealed that infection frequencies positively correlate with telomerase activity in AGS cells but also partly depend on the cellular background. AGS cells with increased telomerase activity showed increased expression mainly of latent EBV genes, suggesting that increased telomerase activity directly acts on the EBV infection of epithelial cells by facilitating latent EBV gene expression early upon virus inoculation. Thus, our results indicate that infection of epithelial cells by EBV is a very selective process involving, among others, telomerase activity and cellular background to allow for optimized host-to-host transmission via saliva. PMID:25856387

  11. N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

    Science.gov (United States)

    Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

    2017-01-01

    Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure

  12. A virtual look at Epstein-Barr virus infection: biological interpretations.

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    Karen A Duca

    2007-10-01

    Full Text Available The possibility of using computer simulation and mathematical modeling to gain insight into biological and other complex systems is receiving increased attention. However, it is as yet unclear to what extent these techniques will provide useful biological insights or even what the best approach is. Epstein-Barr virus (EBV provides a good candidate to address these issues. It persistently infects most humans and is associated with several important diseases. In addition, a detailed biological model has been developed that provides an intricate understanding of EBV infection in the naturally infected human host and accounts for most of the virus' diverse and peculiar properties. We have developed an agent-based computer model/simulation (PathSim, Pathogen Simulation of this biological model. The simulation is performed on a virtual grid that represents the anatomy of the tonsils of the nasopharyngeal cavity (Waldeyer ring and the peripheral circulation--the sites of EBV infection and persistence. The simulation is presented via a user friendly visual interface and reproduces quantitative and qualitative aspects of acute and persistent EBV infection. The simulation also had predictive power in validation experiments involving certain aspects of viral infection dynamics. Moreover, it allows us to identify switch points in the infection process that direct the disease course towards the end points of persistence, clearance, or death. Lastly, we were able to identify parameter sets that reproduced aspects of EBV-associated diseases. These investigations indicate that such simulations, combined with laboratory and clinical studies and animal models, will provide a powerful approach to investigating and controlling EBV infection, including the design of targeted anti-viral therapies.

  13. THE IMPORTANCE OF EPIGENETIC ALTERATIONS IN THE DEVELOPMENT OF EPSTEIN-BARR VIRUS-RELATED LYMPHOMAS

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    Maria Takacs

    2009-11-01

    Full Text Available Epstein-Barr virus (EBV, a human gammaherpesvirus, is associated with a series of malignant tumors. These include lymphomas (Burkitt’s lymphoma, Hodgkin’s disease, T/NK-cell lymphoma, post-transplant lymphoproliferative disease, AIDS-associated lymphoma, X-linked lymphoproliferative syndrome, carcinomas (nasopharyngeal carcinoma, gastric carcinoma, carcinomas of major salivary glands, thymic carcinoma, mammary carcinoma and a sarcoma (leiomyosarcoma. The latent EBV genomes persist in the tumor cells as circular episomes, co-replicating with the cellular DNA once per cell cycle. The expression of latent EBV genes is cell type specific due to the strict epigenetic control of their promoters. DNA methylation, histone modifications and binding of key cellular regulatory proteins contribute to the regulation of alternative promoters for transcripts encoding the nuclear antigens EBNA1 to 6 and affect the activity of promoters for transcripts encoding transmembrane proteins (LMP1, LMP2A, LMP2B. In addition to genes transcribed by RNA polymerase II, there are also two RNA polymerase III transcribed genes in the EBV genome (EBER 1 and 2. The 5’ and internal regulatory sequences of EBER 1 and 2 transcription units are invariably unmethylated. The highly abundant EBER 1 and 2 RNAs are not translated to protein. Based on the cell type specific epigenetic marks associated with latent EBV genomes one can distinguish between viral epigenotypes that differ in transcriptional activity in spite of having an identical (or nearly identical DNA sequence. Whereas latent EBV genomes are regularly targeted by epigenetic control mechanisms in different cell types, EBV encoded proteins may, in turn, affect the activity of a set of cellular promoters by interacting with the very same epigenetic regulatory machinery. There are EBNA1 binding sites in the human genome. Because high affinity binding of EBNA1 to its recognition sites is known to specify sites of DNA

  14. Epstein-Barr Virus: From the Detection of Sequence Polymorphisms to the Recognition of Viral Types.

    Science.gov (United States)

    Feederle, Regina; Klinke, Olaf; Kutikhin, Anton; Poirey, Remy; Tsai, Ming-Han; Delecluse, Henri-Jacques

    2015-01-01

    The Epstein-Barr virus is etiologically linked with the development of benign and malignant diseases, characterized by their diversity and a heterogeneous geographic distribution across the world. The virus possesses a 170-kb-large genome that encodes for multiple proteins and non-coding RNAs. Early on there have been numerous attempts to link particular diseases with particular EBV strains, or at least with viral genetic polymorphisms. This has given rise to a wealth of information whose value has been difficult to evaluate for at least four reasons. First, most studies have looked only at one particular gene and missed the global picture. Second, they usually have not studied sufficient numbers of diseased and control cases to reach robust statistical significance. Third, the functional significance of most polymorphisms has remained unclear, although there are exceptions such as the 30-bp deletion in LMP1. Fourth, different biological properties of the virus do not necessarily equate with a different pathogenicity. This was best illustrated by the type 1 and type 2 viruses that markedly differ in terms of their transformation abilities, yet do not seem to cause different diseases. Reciprocally, environmental and genetic factors in the host are likely to influence the outcome of infections with the same virus type. However, with recent developments in recombinant virus technology and in the availability of high throughput sequencing, the tide is now turning. The availability of 23 complete or nearly complete genomes has led to the recognition of viral subtypes, some of which possess nearly identical genotypes. Furthermore, there is growing evidence that some genetic polymorphisms among EBV strains markedly influence the biological and clinical behavior of the virus. Some virus strains are endowed with biological properties that explain crucial clinical features of patients with EBV-associated diseases. Although we now have a better overview of the genetic

  15. A child with Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis complicated by coronary artery lesion mimicking Kawasaki disease.

    Science.gov (United States)

    Kato, Shogo; Yoshimura, Ken; Tanabe, Yuko; Kimata, Takahisa; Noda, Yukihiro; Kawasaki, Hirohide; Kaneko, Kazunari

    2013-10-01

    There is considerable overlap between hemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD) in terms of aberrant immune response though the etiology of KD remains unknown. We present a case fulfilling the criteria of both HLH and KD complicated by coronary artery dilatation: HLH was confirmed to be triggered by Epstein-Barr virus. This case alarms us the possibility that even patients with HLH may be complicated by coronary artery lesion, which is one of the hallmarks of KD. We would like to draw attention that if features of KD become apparent in patients with HLH, echocardiographic examinations should be performed not to miss coronary artery lesion.

  16. Karyotypic abnormalities associated with Epstein-Barr virus status in classical Hodgkin lymphoma.

    Science.gov (United States)

    Montgomery, Nathan D; Coward, Wilborn B; Johnson, Steven; Yuan, Ji; Gulley, Margaret L; Mathews, Stephanie P; Kaiser-Rogers, Kathleen; Rao, Kathleen W; Sanger, Warren G; Sanmann, Jennifer N; Fedoriw, Yuri

    2016-09-01

    Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors. Here, we report a two-institution retrospective investigation of cytogenetic features characterizing CHL. In our cohort, cases of EBV-negative CHL were characterized by more complex routine karyotypes than their EBV-positive counterparts (24.6 versus 15.6 independent aberrations per case, P = 0.009). The increased complexity of EBV-negative cases was driven by a number of features suggestive of genomic instability, including a larger number of independent chromosomal breakpoints (P = 0.03) and apparently aneuploid autosomes (P = 0.008). Compelling but nonsignificant trends also suggest a larger modal number and increased marker chromosomes in EBV-negative cases (P = 0.13 and 0.06, respectively). While some of these differences are related to histologic subtype, others appear independent of histology. Finally, a significant subset of EBV-positive tumors has a surprisingly simple karyotype relative to what is normally seen in CHL, an observation suggesting considerable biological and genetic diversity in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.

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    Dhananjay M Nawandar

    2015-10-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus associated with B-cell and epithelial cell malignancies. EBV lytically infects normal differentiated oral epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia (OHL in immunosuppressed patients. However, the cellular mechanism(s that enable EBV to establish exclusively lytic infection in normal differentiated oral epithelial cells are not currently understood. Here we show that a cellular transcription factor known to promote epithelial cell differentiation, KLF4, induces differentiation-dependent lytic EBV infection by binding to and activating the two EBV immediate-early gene (BZLF1 and BRLF1 promoters. We demonstrate that latently EBV-infected, telomerase-immortalized normal oral keratinocyte (NOKs cells undergo lytic viral reactivation confined to the more differentiated cell layers in organotypic raft culture. Furthermore, we show that endogenous KLF4 expression is required for efficient lytic viral reactivation in response to phorbol ester and sodium butyrate treatment in several different EBV-infected epithelial cell lines, and that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, is highly synergistic for inducing lytic EBV infection. We confirm that both KLF4 and BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably expressed in B cells, where EBV normally enters latent infection, although KLF4 over-expression is sufficient to induce lytic EBV reactivation in Burkitt lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in mediating lytic EBV reactivation in epithelial cells.

  18. Photodynamic therapy induced production of cytokines by latent Epstein Barr virus infected epithelial tumor cells

    Science.gov (United States)

    Koon, H. K.; Lo, K. W.; Lung, M. L.; Chang, C. K. C.; Wong, R. N. S.; Mak, N. K.

    2007-02-01

    Photodynamic therapy (PDT) is a method to treat cancer or non-cancer diseases by activation of the light-sensitive photosensitizers. Epstein Barr virus (EBV) has been implicated in the development of certain cancers such as nasopharyngeal carcinoma and B cell lymphoma. This study aims to examine the effects of EBV infection on the production of pro-inflammatory cytokines and chemokines in cells after the photosensitizer Zn-BC-AM PDT treatment. Epithelial tumor cell lines HONE-1 and latent EBV-infected HONE-1 (EBV-HONE-1) cells were used in this study. Cells were treated with the photosensitizer Zn-BC-AM for 24 hours before light irradiation. RT-PCR and quantitative ELISA methods were used for the evaluation of mRNA expression and production of cytokines, respectively. Results show that Zn-BC-AM PDT increases the production of IL-1a and IL-1b in EBV-HONE-1. Over a 10-fold increase in the production of IL-6 was observed in the culture supernatant of Zn-BC-AM PDT-treated HONE-1 cells. PDT-induced IL-6 production was observed in HONE-1 cells. EBV-HONE-1 has a higher background level of IL-8 production than the HONE-1. The production of IL-8 was suppressed in EBV-HONE-1cells after Zn-BC-AM PDT. Our results indicate that the response of HONE-1 cells to Zn-BC-AM PDT depends on the presence of latent EBV infection. Since IL-8 is a cytokine with angiogenic activity, Zn-BC-AM PDT may exert an anti-angiogenic effect through the suppression of IL-8 production by the EBV-infected cells.

  19. Evidence of Epstein-Barr virus association with gastric cancer and non-atrophic gastritis.

    Science.gov (United States)

    Martínez-López, Juan L E; Torres, Javier; Camorlinga-Ponce, Margarita; Mantilla, Alejandra; Leal, Yelda A; Fuentes-Pananá, Ezequiel M

    2014-01-20

    Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.

  20. Development of a High-Throughput Screen for Inhibitors of Epstein-Barr Virus EBNA1

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    Thompson, Scott; Messick, Troy; Schultz, David C.; Reichman, Melvin; Lieberman, Paul M.

    2012-01-01

    Latent infection with Epstein-Barr Virus (EBV) is a carcinogenic cofactor in several lymphoid and epithelial cell malignancies. At present, there are no small molecule inhibitors that specifically target EBV latent infection or latency-associated oncoproteins. EBNA1 is an EBV-encoded sequence-specific DNA-binding protein that is consistently expressed in EBV-associated tumors and required for stable maintenance of the viral genome in proliferating cells. EBNA1 is also thought to provide cell survival function in latently infected cells. In this work we describe the development of a biochemical high-throughput screening (HTS) method using a homogenous fluorescence polarization (FP) assay monitoring EBNA1 binding to its cognate DNA binding site. An FP-based counterscreen was developed using another EBV-encoded DNA binding protein, Zta, and its cognate DNA binding site. We demonstrate that EBNA1 binding to a fluorescent labeled DNA probe provides a robust assay with a Z-factor consistently greater than 0.6. A pilot screen of a small molecule library of ~14,000 compounds identified 3 structurally related molecules that selectively inhibit EBNA1, but not Zta. All three compounds had activity in a cell-based assay specific for the disruption of EBNA1 transcription repression function. One of the compounds was effective in reducing EBV genome copy number in Raji Burkitt lymphoma cells. These experiments provide a proof-of-concept that small molecule inhibitors of EBNA1 can be identified by biochemical high-throughput screening of compound libraries. Further screening in conjunction with medicinal chemistry optimization may provide a selective inhibitor of EBNA1 and EBV latent infection. PMID:20930215

  1. Identification of a new class of small molecules that efficiently reactivate latent Epstein-Barr virus

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    Tikhmyanova, Nadezhda; Schultz, David C.; Lee, Theresa; Salvino, Joseph M.; Lieberman, Paul M.

    2014-01-01

    Epstein-Barr Virus (EBV) persists as a latent infection in many lymphoid and epithelial malignancies, including Burkitt's lymphomas, nasopharyngeal carcinomas, and gastric carcinomas. Current chemotherapeutic treatments of EBV-positive cancers include broad- spectrum cytotoxic drugs that ignore the EBV-positive status of tumors. An alternative strategy, referred to as oncolytic therapy, utilizes drugs that stimulate reactivation of latent EBV to enhance the selective killing of EBV positive tumors, especially in combination with existing inhibitors of herpesvirus lytic replication, like Ganciclovir (GCV). At present, no small molecule, including histone deacetylase (HDAC) inhibitors, have proven safe or effective in clinical trials for treatment of EBV positive cancers. Aiming to identify new chemical entities that induce EBV lytic cycle, we have developed a robust high throughput cell-based assay to screen 66,840 small molecule compounds. Five structurally related tetrahydrocarboline derivatives were identified, two of which had EC50 measurements in the range of 150-170 nM. We show that these compounds reactivate EBV lytic markers ZTA and EA-D in all EBV-positive cell lines we have tested independent of the type of latency. The compounds reactivate a higher percentage of latently infected cells than HDAC inhibitors or phorbol esters in many cell types. The most active compounds showed low toxicity to EBV-negative cells, but were highly effective at selective cell killing of EBV-positive cells when combined with GCV. We conclude that we have identified a class of small molecule compounds that are highly effective at reactivating latent EBV infection in a variety of cell types, and show promise for lytic therapy in combination with GCV. PMID:24028149

  2. Evidence of Epstein-Barr Virus Association with Gastric Cancer and Non-Atrophic Gastritis

    Science.gov (United States)

    Martínez-López, Juan L.E.; Torres, Javier; Camorlinga-Ponce, Margarita; Mantilla, Alejandra; Leal, Yelda A.; Fuentes-Pananá, Ezequiel M.

    2014-01-01

    Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger. PMID:24448220

  3. Essential Role of Rta in Lytic DNA Replication of Epstein-Barr Virus

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    Ghiassi-Nejad, Maryam; Golden, Sean; Delecluse, Henri-Jacques; Miller, George

    2013-01-01

    Two transcription factors, ZEBRA and Rta, switch Epstein-Barr virus (EBV) from the latent to the lytic state. While ZEBRA also plays an obligatory role as an activator of replication, it is not known whether Rta is directly required for replication. Rta is dispensable for amplification of an oriLyt-containing plasmid in a transient-replication assay. Here, we assessed the requirement for Rta in activation of viral DNA synthesis from the endogenous viral genome, a function that has not been established. Initially, we searched for a ZEBRA mutant that supports viral replication but not transcription. We found that Z(S186A), a mutant of ZEBRA unable to activate transcription of Rta or viral genes encoding replication proteins, is competent to bind to oriLyt and to function as an origin recognition protein. Ectopic expression of the six components of the EBV lytic replication machinery failed to rescue replication by Z(S186A). However, addition of Rta to Z(S186A) and the mixture of replication factors activated viral replication and late gene expression. Deletion mutagenesis of Rta indicated that the C-terminal 10 amino acids (aa) were essential for the function of Rta in replication. In vivo DNA binding studies revealed that Rta interacted with the enhancer region of oriLyt. In addition, expression of Rta and Z(S186A) together, but not individually, activated synthesis of the BHLF1 transcript, a lytic transcript required for the process of viral DNA replication. Our findings demonstrate that Rta plays an indispensable role in the process of lytic DNA replication. PMID:23077295

  4. Changing patterns in the Epstein-Barr virus (EBV)and Hodgkin lymphoma association in Tunisia.

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    Dhiab, Myriam Ben; Ziadi, Sonia; Saad, Hanene; Louhichi, Teheni; Trimeche, Mounir

    2016-09-01

    We compared the features of the Epstein-Barr virus (EBV) and Hodgkin lymphoma (HL) association in Tunisia in two periods of time, 1991-2001 (111 cases) and 2002-2012 (122 cases). The investigation of the EBV status by EBER in situ hybridization showed a significant decrease in the prevalence of EBV-positive HL from 69.3 % for the period 1991-2001 to 40.1 % for the 2002-2012 period (p = 0.00001). EBV positivity has decreased in all age groups but was more pronounced among young patients, in the 15-24-year age group (46.1 vs 10.3 %, p = 0.003), in the 25-34-year age group (56.2 vs 25 %, p = 0.04), and among children (88.4 vs 59.2 %, p = 0.01). This decrease in EBV-positive HL over time contrasted with a remarkable increase in EBV-negative HL in young adults aged 15-34 years (51.2 vs 83 %; p = 0.001), especially among women (59.1 vs 91.2 %; p = 0.01). The decrease in EBV-positive HL over time concerns particularly the nodular sclerosis histological subtype (69.2 vs 31.6 %, p = 0.000001). These results indicate that the epidemiology of HL and its association with EBV are changing over time, with a trend toward a Western profile, and point toward the emergence of other environmental causative factors, especially among young women, which remain to be identified.

  5. Infectious mononucleosis due to epstein-barr virus infection in children: A profile from eastern India

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    Madhumita Nandi

    2017-01-01

    Full Text Available Objective: The objective of this study is to delineate the clinical and laboratory profile of infectious mononucleosis due to Epstein-Barr virus (EBV infection in children admitted to tertiary care teaching hospitals. Materials and Methods: Retrospective observational multicentric analysis of clinical and laboratory features of children between 1 month to 12 years with a diagnosis of infectious mononucleosis due to EBV infection confirmed by positive serology over a 12-month period after seeking approval from the Institutional Ethics Committee. Results: Out of 66 children screened, 53 were included in final analysis. The majority were aged between 5 and 8 years with male: female ratio of 1.2:1. Most presentations were during the monsoon months. The common clinical features were fever (100%, splenomegaly (86.7%, and cervical lymphadenopathy (73.5% in contrast to the classical triad of fever, sore throat, and generalized lymphadenopathy described in the literature. There were no age differences in clinical findings except for generalized and cervical lymphadenopathy and hepatomegaly which were commoner in 9–12 years age band. Although the incidence of common findings matched with previously published studies, there were some notable differences. While frequencies of upper eyelid edema, epitrochlear lymphadenopathy, and splenomegaly were more, those of rash and sore throat were less. Lymphocytosis and presence of atypical lymphocytes were relatively less common in our series. All children recovered. Conclusions: This multicentric study on profiling childhood infectious mononucleosis, possibly first of its kind from Eastern India, has documented clinical and laboratory features associated with this condition. These data can serve as a reference for future studies.

  6. Prevalence of human papillomavirus and Epstein-Barr virus DNA in penile cancer cases from Brazil

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    Larissa Alves Afonso

    2012-02-01

    Full Text Available Penile cancer is a potentially mutilating disease. Although its occurrence is relatively rare worldwide, penile cancer rates can be high in developing countries. A few studies have been conducted on the involvement of human papillomavirus (HPV in penile carcinoma, which have found HPV present in 30-70% of penile malignant lesions, with a higher prevalence of HPV 16 and 18. It has been assumed that cofactors, such as Epstein-Barr virus (EBV infections, may play a role in the progression of penile neoplasia. The aim of this study was to determine HPV and EBV prevalence in 135 penile malignant lesions from Brazilian men through the use of MY09/11 polymerase chain reaction (PCR, type-specific PCR and restriction fragment length polymorphism analysis. HPV prevalence among the men tested was 60.7%. Of the men who tested positive, 27 presented with HPV 16 (29.7%, five with HPV 18 (5.5%, 21 with HPV 45 (23.1% and nine with HPV 6 (9.9%. Seven mixed infections were detected (9.2%, while 11 cases remained untyped (13.4%. Regarding EBV positivity, 46.7% of the samples contained EBV DNA with EBV-1 as the most prevalent type (74.6%. More than 23% of the men were co-infected with both HPV and EBV, while 35% presented exclusively with HPV DNA and 20% presented only with EBV DNA. Penile carcinoma aetiology has not been fully elucidated and the role of HPV and EBV infections individually or synergistically is still controversial. Hence, more studies are needed to determine their possible role in carcinogenesis.

  7. Manifestaciones oftalmológicas por virus de Epstein-Barr

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    Adrianne MayulySuñetÁlvarez

    Full Text Available Se trata de un paciente masculino de 26 años que acude por disminución brusca de la visión del ojo derecho. Seingresó como una uveítis posterior dada por exudación extensa en área macular del ojo derecho, acompañada de edema del disco óptico, vasculitis aledaña a la lesión y hemorragias dispersas en llama en el polo posterior. La etiología era controversial y, el tratamiento más apropiado era debatible, por lo que se le realizaron estudios como retinografías seriadas, angiografías fluoresceínicas y reacción en cadena de polimerasa a una muestra del humor acuoso, que confirmó la etiología viral; lo que resultó en una agudeza visual final de 0,1. Posterior a 6 meses del cuadro inicial, el paciente presentó queratitis intraestromal en forma numular -que recurre ante episodios de stress-, para desaparecer luego de terapia tópica con antiinflamatorios no esteroideos y esteroideos.La baja incidencia de casos reportados con uveítis posterior por virus de Epstein Barr resulta de un pobre conocimiento de la presentación de la enfermedad, por tanto un retraso en la instauración del tratamiento. En estos casos la prueba de oro es la reacción de cadena de polimerasa.

  8. Lack of Association between Epstein-Barr Virus and Epithelial Malignancies Developed after Kidney Transplantation.

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    Seo, Jung Seon; Kang, Kyeong Hee; Kang, Jin Hyoung; Lee, Suk Kyeong

    2003-10-01

    Organ transplant recipients are at high risk of developing malignancies due to immunosuppressive regimens. Unlike post-transplant lymphoproliferative diseases (PTLDs), where Epstein-Barr virus (EBV) plays an etiological role, there are conflicting data regarding the association of EBV with post-transplant epithelial malignancies. In order to clarify the role of EBV in carcinomas that develop after solid-organ transplantation, the presence of EBV infection in the carcinomas of post-kidney transplant patients was examined. The presence of EBV infection in skin carcinoma (PTSC), gastric carcinoma (PTGC) and urothelial carcinoma (PTUC), which developed in the patients under an immune suppression regime following kidney transplantation, was examined. Tumors from the patients without organ transplantation were also used as a comparison in the study. The study group included five nasopharyngeal carcinomas (NPCs), one Hodgkin's disease (HD), one B-cell non-Hodgkin's malignant lymphoma (NHL) and one hypopharynx (HPC) tumor. Immunofluorescence assay and Western blot analysis, using sera from the same patients, confirmed that all of the tested patients were previously infected with EBV. From in situ hybridization, no EBER positive cells were detected in any of the tumor tissues obtained from the three kidney transplant recipients (PTSC, PTGC and PTUC) or in the NHL and HPC tissues. In contrast, all five of the NPC and HD tissues showed strong EBER positivity. These results suggest that there is a strong association of EBV with NPC and HD as previously reported, while no such strong association of EBV was found with epithelial malignancies that developed after kidney transplantation.

  9. Epstein-Barr virus associated gastric carcinoma: a report from Iran in the last four decades

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    Mosavi-Jarrahi Alireza

    2007-07-01

    Full Text Available Abstract Background Epstein-Barr virus has been proved to be associated with many of the human malignancy including gastric carcinoma, one of the most important human malignancies in the world. There has been no study about the presence of EBV in gastric adenocarcinoma in Iran. Methods We examined the presence of EBV in 273 formalin fixed paraffin-embedded cases of gastric carcinoma from Cancer institute of Tehran University, from 1969 to 2004. In situ hybridization of EBV-encoded small RNA-1 (EBER-1 was conducted. The strain of positive cases was examined by means of polymerase chain reaction and/or restriction fragment length polymorphism analysis. Results We found 9 (3%; 95% CI = 1–5% EBV positive cases. The gender difference was not statisticaly significant. The proportion of EBV-GC cases in diffuse type was higher than intestinal type (OR = 0.08; 95% CI = 0.002–0.64. EBV-GC cases had no relation with age, location and invasion. Six out of 9 EBV-GC cases were born during the period between 1928 and 1930. All 9 cases were Type A. Prototype F was seen in 6 out of 8 cases. Type "i" was found in 8 cases and type I in 1 case. XhoI+ and XhoI- polymorphism accounted 6 and 3 of the cases, respectively. Conclusion Our study is the first to describe the frequency of EBV-GC in Iran and the Middle East, highlighting a very low prevalence with specific clinicopathologic features. The predominance of EBV-GC birth year in a fixed period, suggests that EBV infection or other events at early childhood may be related to the development of EBV-GC later in the life. The predominance of the type "i" and XhoI+ cases are contradictory to other studies in Asia and is similar to what is reported from Latin American countries.

  10. Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer.

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    Chia, Marie C; Leung, Abby; Krushel, Tiffany; Alajez, Nehad M; Lo, Kwok W; Busson, Pierre; Klamut, Henry J; Bastianutto, Carlo; Liu, Fei-Fei

    2008-02-15

    The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes. The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model. C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 microg/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences. Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression. These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.

  11. Detection of autoimmunity in early primary Epstein-Barr virus infection by Western blot analysis.

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    Mascia, M T; Sandri, G; Guerzoni, C; Roncaglia, R; Mantovani, G; Ferri, C

    2008-01-01

    The Epstein-Barr virus (EBV) represents a potentially important factor in the pathogenesis of certain autoimmune disorders such as systemic lupus erythematosus (SLE), and Sjögren's syndrome, probably through a molecular mimicry mechanism. Several studies have focused on the relationship between previous EBV infection and clinically overt connective tissue diseases (CTDs), while the aim of this study was to investigate the immunological alterations during the early phase of primary acute EBV infection by means of ENA Western blotting (WB) analysis. This technique is able to detect a wide spectrum of anti-ENA autoantibodies, potentially directed against diverse epitopes of the same antigen. Sera from 54 subjects (F/M=24/30, mean age 17+/-6 SD years) with primary acute EBV infection were analysed using indirect immunofluorescence (IF) on Hep-2 cells for ANA, and both ELISA and WB for ENA. Only 8 ANA+ and no ENA+ were found by means of IF and ELISA techniques, respectively; however, one or more ENA autoantibodies were detected in 24/54 (44%) sera using WB. The autoantibodies were no longer present at the second evaluation. Subjects with immunological alterations had not developed any significant clinical manifestations at a 5-year follow-up. This study demonstrated the appearance of autoantibody production in a high proportion of individuals with primary acute EBV infection; interestingly, the observed serological subsets are quite similar to clinical SLE clusters. Moreover, the absence of immunological disorders during the follow-up reinforces the role of multiple genetic and/or environmental co-factors in the pathogenesis of CTDs.

  12. Epstein-Barr virus-encoded BARF1 protein is a decoy receptor for macrophage colony stimulating factor and interferes with macrophage differentiation and activation

    NARCIS (Netherlands)

    Hoebe, Eveline K.; Le Large, Tessa Y. S.; Tarbouriech, Nicolas; Oosterhoff, Dinja; de Gruijl, Tanja D.; Middeldorp, Jaap M.; Greijer, Astrid E.

    2012-01-01

    Epstein-Barr virus (EBV), like many other persistent herpes viruses, has acquired numerous mechanisms for subverting or evading immune surveillance. This study investigates the role of secreted EBV-encoded BARF1 protein (sBARF1) in creating an immune evasive microenvironment. Wild-type consensus

  13. Lack of Epstein-Barr virus- and HIV-specific CD27- CD8+ T cells is associated with progression to viral disease in HIV-infection

    NARCIS (Netherlands)

    van Baarle, Debbie; Kostense, Stefan; Hovenkamp, Egbert; Ogg, Graham; Nanlohy, Nening; Callan, Margaret F. C.; Dukers, Nicole H. T. M.; McMichael, Andrew J.; van Oers, Marinus H. J.; Miedema, Frank

    2002-01-01

    OBJECTIVE: Despite readily detectable virus-specific CD8+ T cells in most HIV-infected patients, immune surveillance is eventually lost, leading to progression to AIDS. To investigate the underlying mechanism of this loss of immune control phenotypic analysis of HIV- and Epstein-Barr virus

  14. Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

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    Kano, Kohei; Katayama, Takayuki; Takeguchi, Shiori; Asanome, Asuka; Takahashi, Kae; Saito, Tsukasa; Sawada, Jun; Saito, Masato; Anei, Ryogo; Kamada, Kyousuke; Miyokawa, Naoyuki; Nishihara, Hiroshi; Hasebe, Naoyuki

    2017-06-01

    A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis. © 2016 Japanese Society of Neuropathology.

  15. Detection of Epstein Barr Virus by Chromogenic In Situ Hybridization in cases of extra-hepatic biliary atresia

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    Farahmand Fatemeh

    2008-04-01

    Full Text Available Abstract Introduction Extra-hepatic biliary atresia (EHBA is an important cause of neonatal cholestasis. Several infectious agents have been proposed as etiologic factors such as Rotavirus and Reovirus. There is limited data on the role of Epstein Barr virus (EBV infection in EHBA, so we decided to study the presence of EBV virus in a series of 16 proven EHBA cases by Chromogenic in situ hybridization (CISH technique. Methods In the current study a total of 16 liver wedge biopsies of proven cases of EHBA were selected in a period of 4 years. CISH staining for EBV-encoded RNA (EBER transcript was performed. Results The review of H&E-stained slides of liver biopsies revealed fibrosis and marked ductular proliferation. In CISH-stained slides, EBV trace was observed in hepatocytes in two cases and in biliary epithelium in one case of EHBA. Discussion Considering the association of hepatitis with the Epstein-Barr virus in later life, it is likely that EBV hepatitis and its complications occur in the neonatal/perinatal period. Since EHBA is a relatively rare disease, a similar study on wedge biopsies of this number of proven cases of EHBA has not been performed to date. Current observation proposes the need for a study of larger series and employing other methods for confirming the etiologic role of EBV in EHBA cases.

  16. The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.

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    Samantha K Dunmire

    2015-12-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV's lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset-coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in

  17. Epstein-Barr Virus BKRF4 Gene Product Is Required for Efficient Progeny Production.

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    Masud, H M Abdullah Al; Watanabe, Takahiro; Yoshida, Masahiro; Sato, Yoshitaka; Goshima, Fumi; Kimura, Hiroshi; Murata, Takayuki

    2017-12-01

    Epstein-Barr virus (EBV), a member of human gammaherpesvirus, infects mainly B cells. EBV has two alternative life cycles, latent and lytic, and is reactivated occasionally from the latent stage to the lytic cycle. To combat EBV-associated disorders, understanding the molecular mechanisms of the EBV lytic replication cycle is also important. Here, we focused on an EBV lytic gene, BKRF4. Using our anti-BKRF4 antibody, we revealed that the BKRF4 gene product is expressed during the lytic cycle with late kinetics. To characterize the role of BKRF4, we constructed BKRF4-knockout mutants using the bacterial artificial chromosome (BAC) and CRISPR/Cas9 systems. Although disruption of the BKRF4 gene had almost no effect on viral protein expression and DNA synthesis, it significantly decreased progeny virion levels in HEK293 and Akata cells. Furthermore, we show that BKRF4 is involved not only in production of progeny virions but also in increasing the infectivity of the virus particles. Immunoprecipitation assays revealed that BKRF4 interacted with a virion protein, BGLF2. We showed that the C-terminal region of BKRF4 was critical for this interaction and for efficient progeny production. Immunofluorescence analysis revealed that BKRF4 partially colocalized with BGLF2 in the nucleus and perinuclear region. Finally, we showed that BKRF4 is a phosphorylated, possible tegument protein and that the EBV protein kinase BGLF4 may be important for this phosphorylation. Taken together, our data suggest that BKRF4 is involved in the production of infectious virions. IMPORTANCE Although the latent genes of EBV have been studied extensively, the lytic genes are less well characterized. This study focused on one such lytic gene, BKRF4, which is conserved only among gammaherpesviruses (ORF45 of Kaposi's sarcoma-associated herpesvirus or murine herpesvirus 68). After preparing the BKRF4 knockout virus using B95-8 EBV-BAC, we demonstrated that the BKRF4 gene was involved in infectious

  18. Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis and Guillain-Barre Syndrome in a 16-Month-Old Child.

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    Matsui, Motohiro; Shimizu, Mariko; Ioi, Aya; Mayumi, Azusa; Higuchi, Kohei; Sawada, Akihisa; Sato, Maho; Yasui, Masahiro; Yanagihara, Keiko; Inoue, Masami

    2016-01-01

    A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic lymphohistiocytosis and transferred to our hospital on the 58th day of the hemophagocytic lymphohistiocytosis after treatment failure according to the Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital, she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was established. Intravenous immunoglobulin G was started on the 57th day of the Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen (pirarubicin, cyclophosphamide, vincristine, and prednisone) and 2 courses of ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase), we are now in the process of coordinating unrelated umbilical cord blood transplantation. To the best of our knowledge, we report the youngest case of Guillain-Barre syndrome accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid progression of Guillain-Barre syndrome, the electrophysiological subtype of Guillain-Barre syndrome, and treatment delay possibly led to poor neurological outcome.

  19. Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis and Guillain-Barre Syndrome in a 16-Month-Old Child

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    Motohiro Matsui MD

    2016-03-01

    Full Text Available A 16-month-old girl was diagnosed with Epstein-Barr virus hemophagocytic lymphohistiocytosis and transferred to our hospital on the 58th day of the hemophagocytic lymphohistiocytosis after treatment failure according to the Hemophagocytic Lymphohistiocytosis-2004 protocol. On admission to our hospital, she had a flaccid paralysis of her lower limbs. Nerve conduction studies showed a acute motor axonal neuropathy, and a diagnosis of Guillain-Barre syndrome was established. Intravenous immunoglobulin G was started on the 57th day of the Guillain-Barre syndrome. To date, her neurological recovery is incomplete. For hemophagocytic lymphohistiocytosis, after treatment failure of THP-COP regimen (pirarubicin, cyclophosphamide, vincristine, and prednisone and 2 courses of ESCAP regimen (etoposide, prednisone, cytarabine, L-asparaginase, we are now in the process of coordinating unrelated umbilical cord blood transplantation. To the best of our knowledge, we report the youngest case of Guillain-Barre syndrome accompanied by Epstein-Barr virus hemophagocytic lymphohistiocytosis. Rapid progression of Guillain-Barre syndrome, the electrophysiological subtype of Guillain-Barre syndrome, and treatment delay possibly led to poor neurological outcome.

  20. Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.

    Science.gov (United States)

    Ballard, Ashley James

    2015-12-01

    The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Spontaneous Remission of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly

    Directory of Open Access Journals (Sweden)

    T. Mizuno

    2013-05-01

    Full Text Available A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R. Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.

  2. Detection of human papillomavirus and Epstein-Barr virus DNA sequences in oral mucosa of HIV-infected patients by the polymerase chain reaction.

    Science.gov (United States)

    Snijders, P. J.; Schulten, E. A.; Mullink, H.; ten Kate, R. W.; Jiwa, M.; van der Waal, I.; Meijer, C. J.; Walboomers, J. M.

    1990-01-01

    The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) was analyzed in 21 oral biopsy specimens of HIV-infected patients using the polymerase chain reaction (PCR) method. Biopsies were categorized as hairy leukoplakia (HL) (n = 12), candidiasis (n = 3), oral warts (n = 2), and clinically normal epithelium (n = 4). For HPV detection a modified general primer-mediated PCR method (GP-PCR), which detects a broad spectrum of HPV genotypes at sub-picogram levels, was used. Human papillomavirus DNA was only found in two oral warts and was identified as HPV type 32. Epstein-Barr virus DNA was detected in 16 biopsy specimens, including the 12 HLs, 2 cases of candidiasis, and 2 samples of normal epithelium. Epstein-Barr virus positivity in HL could be confirmed by Southern blot analysis and DNA in situ hybridization using biotinylated DNA probes (bio-DISH). Epstein-Barr virus bio-DISH was also positive in one sample of normal epithelium from a patient with HL. The results indicate that HL is strongly associated with EBV and not with any of the common HPV types that react with general HPV primers in the PCR. However the detection of EBV in normal oral epithelium by PCR and bio-DISH suggests that the presence of this virus is not exclusively related to HL. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2169191

  3. Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study.

    Science.gov (United States)

    Torniainen-Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H

    2018-03-01

    Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. Copyright © 2018. Published by Elsevier Inc.

  4. Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1.

    Science.gov (United States)

    Wang, Qianli; Lingel, Amy; Geiser, Vicki; Kwapnoski, Zachary; Zhang, Luwen

    2017-10-15

    Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and

  5. Surgical Treatment for Epstein-Barr Virus Otomastoiditis Complicated by Facial Nerve Paralysis: A Case Report of Two Young Brothers and Review of Literature

    NARCIS (Netherlands)

    Eeten, E. van; Faber, H.T.; Kunst, D.

    2017-01-01

    We report the case of two young brothers with Epstein-Barr virus (EBV) otomastoiditis complicated by a facial nerve paralysis. The boys, aged 7 months (patient A) and 2 years and 8 months (patient B), were diagnosed with a facial nerve paralysis House-Brackmann (HB) grade IV (A) and V (B). After

  6. Cell transformation mediated by the Epstein-Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling

    DEFF Research Database (Denmark)

    Lyngaa, Rikke Birgitte; Nørregaard, K.; Kristensen, Martin

    2010-01-01

    Epstein-Barr virus (EBV) open reading frame BILF1 encodes a seven trans-membrane (TM) G protein-coupled receptor that signals with high constitutive activity through G alpha(i) (Beisser et al., 2005; Paulsen et al., 2005). In this paper, the transforming potential of BILF1 is investigated in vitro...

  7. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients

    NARCIS (Netherlands)

    Stevens, SJC; Verschuuren, EAM; Pronk, [No Value; van der Bij, W; Harmsen, MC; The, TH; Meijer, CJLM; van den Brule, AJC; Middeldorp, JM

    2001-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)-associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function, The diagnostic value of weekly EBV DNA load monitoring was investigated in

  8. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries

    DEFF Research Database (Denmark)

    Ok, Chi Young; Li, Ling; Xu-Monette, Zijun Y

    2014-01-01

    PURPOSE: Epstein-Barr virus-positive (EBV(+)) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV(+) DLBCL, independent of age...

  9. Diverse IgG serum response to novel glycopeptide epitopes detected within immunodominant stretches of Epstein-Barr virus glycoprotein 350/220

    DEFF Research Database (Denmark)

    D'Arrigo, Isotta; Cló, Emiliano; Bergström, Tomas

    2013-01-01

    The Epstein-Barr virus (EBV) envelope glycoprotein 350/220 (gp350/220) is the most abundant molecule on the viral surface and it is responsible for the initial viral attachment to cell surface of the host. As many other viral envelope proteins, it is highly glycosylated, not least with O...

  10. The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma

    DEFF Research Database (Denmark)

    Anderton, J A; Bose, S; Vockerodt, M

    2011-01-01

    ), an Epstein-Barr virus (EBV) associated malignancy. KDM6B is over-expressed in primary HL and induced by the EBV oncogene, latent membrane protein (LMP1) in GC B cells, the presumptive progenitors of HL. Consistent with these observations, we found that KDM6B transcriptional targets in GC B cells are enriched...

  11. Co-existence of Chiari malformation type I and Epstein-Barr virus meningoencephalitis in a 3-year-old child: case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Solomou, E.K.; Kotsarini, C.; Badra, F.A. [University Hospital of Patras, Department of Radiology, Rio (Greece); Krepis, A.; Papanastasiou, D. [University Hospital of Patras, Pediatric Clinic, Patras (Greece); Patriarcheas, G. [Diagnostic Centre B Diagnosis, Patras (Greece)

    2005-01-01

    In the present report we describe an unusual case of a 3-year-old girl who was admitted to our hospital with Epstein-Barr virus meningoencephalitis. Brain magnetic resonance imaging revealed diffuse abnormalities in white matter and Chiari I malformation with cervical and thoracic hydro-syringomyelia. (orig.)

  12. Different pattern of allelic loss in Epstein-Barr virus-positive gastric cancer with emphasis on the p53 tumor suppressor pathway

    NARCIS (Netherlands)

    van Rees, Bastiaan P.; Caspers, Eric; zur Hausen, Axel; van den Brule, Adriaan; Drillenburg, Paul; Weterman, Marian A. J.; Offerhaus, G. Johan A.

    2002-01-01

    Both Helicobacter pylori (HP) and Epstein-Barr virus (EBV) have been implicated in carcinogenesis of the stomach. Fifty-seven gastric carcinomas were tested for microsatellite instability and allelic loss at several tumor suppressor loci using 21 polymorphic microsatellite markers. Furthermore,

  13. Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment

    Directory of Open Access Journals (Sweden)

    Massimiliano Castellazzi

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV sustained by the levels of antiviral capsid antigen (VCA and anti-Epstein-Barr nuclear antigen-1 (EBNA-1 IgG has been described. Our goal was to verify the utility of EBV-specific IgG as a marker in Natalizumab treated MS. Twenty patients (17 female and 3 male in treatment with Natalizumab were enrolled. Serum levels of anti-VCA and anti-EBNA-1 IgG were determined and expressed as arbitrary units (AU before treatment and every three months for 21 months of therapy. Anti-VCA IgG levels were increased at the 15th month (235410 ± 196712 AU comparing with the 3rd (98146 ± 47145 AU and the 6th (109866 ± 52270 AU months of therapy p<0.05. No significant differences were found for serum anti-EBNA-1 IgG levels. Our data indicate that a transient, self-limited, EBV reactivation can occur in MS during Natalizumab therapy but our results do not support the use of serum EBV-specific antibody levels as biomarkers for monitoring therapeutic response to Natalizumab in the course of MS.

  14. Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.

    Science.gov (United States)

    El-Naby, Noha Ed Hassab; Hassan Mohamed, Hameda; Mohamed Goda, Asmaa; El Sayed Mohamed, Ahmed

    2017-06-01

    A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature. We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center. This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls. Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003. Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  15. Expression of Epstein-Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco-chewing population.

    Science.gov (United States)

    Reddy, Sujatha S; Sharma, Shivani; Mysorekar, Vijaya

    2017-07-01

    Oral cancer is the sixth most common malignancy in the world. Viruses are the causative agents of approximately 10-15% of all cancers worldwide (Cancers, 6, 2014 and 2155). The tumorigenic roles of Epstein-Barr virus in oral cancer are unclear. Literature search results are conflicting and dependent on various factors such as geographical/regional variations, sociocultural lifestyles, dietary habits, chewing/smoking tobacco habit. This study is the first original observation about frequency of Epstein-Barr virus among South Indian tobacco-chewing patients to elucidate its involvement in oral carcinogenesis and to know whether this can be a valuable diagnostic and prognostic indicator. A total number of 75 tobacco chewer subjects aged between 23 and 76 years with histopathologically confirmed oral potentially malignant disorders (25), oral squamous cell carcinoma (25), and age-matched healthy controls (25) formed the study group. Immunohistochemical expression of Epstein-Barr virus latent membrane protein 1 was assessed among cases and healthy controls. Out of the total 75 subjects, six subjects (8%) were positive for Epstein-Barr virus antigen and 69 subjects (92%) negative. The antigen positivity was observed among two cases of moderately differentiated oral squamous cell carcinoma, two cases of leukoplakia, and two healthy controls. No significant association between Epstein-Barr virus positivity was observed among oral potentially malignant disorders and oral squamous cell carcinoma among South Indian tobacco-chewing patients. This can be partially explained by the methodology employed, by the patient population analyzed and different habits in various geographical regions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Improvement of therapy for escherichiosis in children infected with Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Ye.S. Olkhovskyy

    2017-03-01

    Full Text Available Background. Escherichiosis remains one of the most common intestinal infections, especially among young children. Indigestion of essential nutrients, transient fermentopathy, imbalance of the symbiotic flora, which develop in escherichiosis in combination with general intoxication and water-electrolyte disturbances, can lead to unfavorable outcomes. One of the factors influencing the course of escherichiosis can be Epstein-Barr virus (EBV infection in the child. Purpose of the research — improvement of treatment of children with escherichiosis and EBV infection in different periods of the disease. Materials and methods. We examined 74 children aged 2–3 years, who were treated at the Regional Children’s Clinical Infectious Diseases Hospital in Kharkiv with a diagnosis of moderate-to-severe escherichiosis. A group of 36 children was selected, who received conventional therapy with early gradual restoration of nutrition according to the existing protocol, and the restoration of the qualitative and quantitative composition of food was carried out as soon as possible (first group. The second group was represented by 38 children, who received two-day prolonged gradual restoration of the diet: more gradual increasing the volume of food at each feeding and reducing the number of feedings per day. Children of the second group received drugs containing Lactobacillus, milk thistle extract and B vitamins (once daily with meals from the first day. Ultrasound examination of the abdominal cavity was performed in all children. Results. Analysis of the main clinical, laboratory and instrumental parameters of patients in both groups during their stay in the hospital and one month after the discharge from the hospital revealed that in children of the second group, in whom rational diet therapy was applied, there was a reduction in the duration of bowel dysfunction, abdominal syndrome, flatulence; the parameters of the coprological test and the echosonoscopy

  17. Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

    International Nuclear Information System (INIS)

    Kim, Sun Young; Song, Kyung-A; Kieff, Elliott; Kang, Myung-Soo

    2012-01-01

    Highlights: ► Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. ► A small molecule and a peptide as EBNA1 dimerization inhibitors identified. ► Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. ► Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)’s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459–607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-Jκ binding to the Jκ site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560–574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated with EBNA1 in vitro, and repressed EBNA1-dependent transcription in vivo. Collectively, this study describes two

  18. Epstein-Barr virus and human papillomavirus infections and genotype distribution in head and neck cancers.

    Directory of Open Access Journals (Sweden)

    Zeyi Deng

    Full Text Available To investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV and human papillomavirus (HPV infections in Japanese patients with different types of head and neck cancer (HNC.HPV and EBV DNA, EBV genotypes and LMP-1 variants, and HPV mRNA expression were detected by PCR from fresh-frozen HNC samples. HPV genotypes were determined by direct sequencing, and EBV encoded RNA (EBER was examined by in situ hybridization.Of the 209 HNC patients, 63 (30.1% had HPV infection, and HPV-16 was the most common subtype (86.9%. HPV E6/E7 mRNA expression was found in 23 of 60 (38.3% HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%. Among 146 (69.9% HNCs in which EBV DNA was identified, 107 (73.3% and 27 (18.5% contained types A and B, respectively, and 124 (84.9% showed the existence of del-LMP-1. However, only 13 (6.2% HNCs were positive for EBER, 12 (92.3% of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC patients than in the other OPC patients (P = 0.027 and 0.017, respectively. Multivariate analysis showed that stage T1-3 (P = 0.002 and HPV mRNA-positive status (P = 0.061 independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155.Our findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.

  19. Epstein - Barr virus expression in Hodgkin's disease: Correlation withhistologic subtypes and T and B lymphocyte distribution

    International Nuclear Information System (INIS)

    Mourad, W.; Bazerbashi, S.; Alsohaibani, Mohamed O.; Saddik, M.

    1998-01-01

    The pathogenesis of Hodgkin's disease is linked to Epstein-Barr virus(EBV). Some histologic subtypes show a high level of viral expression. Theseinclude mixed cellularity (MCHD) and nodular sclerosis (NSHD) subtypes. GradeII NSHD is a more aggressive variant of HD. Lymphocyte predominant (LPHD) isa B cell lymphoproliferative disorder that has not been associated with EBVexpression. Infiltrating lymphocytes in HD are predominantly T lymphocytes,with minor component of B lymphocytes. In the current study, EBV expressionwas tested in cases of HD in relation to histologic subtypes. An attempt wasmade at correlating EBV expression with T and B lymphocyte distribution inlymph nodes involved by HD. Formalin-fixed paraffin-embedded tissue from 62cases of HD were tested for EBV and mRNA expression, using the EBER-1 probeand in situ hybridization. T and B lymphocyte distribution and their ratioswere evaluated using antibodies to T and B lymphocytes (UCHL-1 [CD45RO] andCD20, respectively), and the immunoperoxidase technique. The cases were seenin 38 male and 24 female patients, with an age range of 3 to 72 years (median25 years). There were 30 cases of grade I and 15 cases of grade II NSHD, 9cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases(46%). This expression was seen in 8 cases of grade I NSHD (26%), 13 cases ofgrade II NSHD (86%) and 8 cases of MCHD (88%). None of the cases of LPHDshowed viral expression. T to B lymphocytes ratios in EBV-positive casesranged from 1/6 to 8/1 and ranged from 2/1 to 20/1 in EBV-negative cases(P=0.06). Nine of the 29 positive cases (31%) showed equal T/B lymphocyteratios (n=4), or predominance of B lymphocytes (n=5). None of theEBV-negative cases showed predominance of B lymphocytes. Our study confirmedpreviously reported findings of the prevalence of EBV expression in MCHD andNSHD. Our findings also suggest that EBV expression may be more commonly seenin aggressive forms of HD. Decreased number of T lymphocytes in

  20. Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Young; Song, Kyung-A [Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kieff, Elliott [Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Kang, Myung-Soo, E-mail: mkang@skku.edu [Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. Black-Right-Pointing-Pointer A small molecule and a peptide as EBNA1 dimerization inhibitors identified. Black-Right-Pointing-Pointer Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. Black-Right-Pointing-Pointer Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)'s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459-607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-J{kappa} binding to the J{kappa} site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560-574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated

  1. Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.

    Science.gov (United States)

    Correia, Samantha; Palser, Anne; Elgueta Karstegl, Claudio; Middeldorp, Jaap M; Ramayanti, Octavia; Cohen, Jeffrey I; Hildesheim, Allan; Fellner, Maria Dolores; Wiels, Joelle; White, Robert E; Kellam, Paul; Farrell, Paul J

    2017-08-01

    Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV) strains, including many primary isolates, have been used to investigate variation in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART microRNA (miRNA) cluster 2. Determination of type 1 and type 2 EBV in saliva samples from people from a wide range of geographic and ethnic backgrounds demonstrates a small percentage of healthy white Caucasian British people carrying predominantly type 2 EBV. Linkage of Zp and gp350 variants to type 2 EBV is likely to be due to their genes being adjacent to the EBNA3 locus, which is one of the major determinants of the type 1/type 2 distinction. A novel classification of EBNA1 DNA binding domains, named QCIGP, results from phylogeny analysis of their protein sequences but is not linked to the type 1/type 2 classification. The BART cluster 2 miRNA region is classified into three major variants through single-nucleotide polymorphisms (SNPs) in the primary miRNA outside the mature miRNA sequences. These SNPs can result in altered levels of expression of some miRNAs from the BART variant frequently present in Chinese and Indonesian nasopharyngeal carcinoma (NPC) samples. The EBV genetic variants identified here provide a basis for future, more directed analysis of association of specific EBV variations with EBV biology and EBV-associated diseases. IMPORTANCE Incidence of diseases associated with EBV varies greatly in different parts of the world. Thus, relationships between EBV genome sequence variation and health, disease, geography, and ethnicity of the host may be important for understanding the role of EBV in diseases and for development of an effective EBV vaccine. This paper provides the most comprehensive analysis so far of variation in specific EBV genes relevant to these diseases and proposed EBV vaccines. By focusing on variation in LMP1, Zp, gp350, EBNA1, and the BART miRNA cluster 2, new relationships with the known

  2. Influence of Quillaja saponaria triterpenoid content on the immunomodulatory capacity of Epstein-Barr virus iscoms.

    Science.gov (United States)

    Dotsika, E; Karagouni, E; Sundquist, B; Morein, B; Morgan, A; Villacres-Eriksson, M

    1997-03-01

    The immune responses to immunostimulating complexes (iscoms) containing recombinant Epstein-Barr virus (EBV) gp340 envelope protein was evaluated in BALB/c (H-2(d)) and CBA (H-2(k)) mice. Gp340-iscoms were used either with a low content of Quillaja triterpenoid adjuvant (L-iscoms) or supplemented with additional Quillaja adjuvant in the form of iscomatrix (S-iscoms). Class and subclass distribution of anti-gp340 antibodies, EBV-neutralizing antibodies, antigen-specific T cell proliferation and cytokine production were determined and these results compared to those obtained by immunization with non-adjuvated gp340. The H-2(d) and H-2(k) mice were characterized as low or high responders in respect to the level of specific anti-gp340 antibodies, secretion of IgG2a isotype, antigen-specific lymphoproliferative capacity, interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) production in the basic immunizations with gp340. While presentation of the antigen in iscom formulations with low levels of Quillaja triterpenoids induces a moderate enhancement of the immune responses in the low responder H-2(d) mice, supplementation with high levels of iscomatrix immunomodulator was required to enhance the immune responses in the high responder H-2(k) mice. In both mouse strains subcutaneous immunization with S-iscoms resulted in a significant increase of IgG1- and IgG2a-specific antibodies, as well as in strong antigen-specific proliferative response confirmed by the simultaneous cytokine production. The enhanced antigen-specific secretion of IL-2 and IFN-gamma together with the abrogation of IL-10 and the absence of IL-4 indicates that the responses were driven towards a Th1-type rather than Th2-type immune response. The S-iscom formulations minimized the differences in immune responses between the two mouse strains, but the capacity of immune sera to neutralize EBV transformation in vitro remained completely strain-dependent. These data indicate that immune responses

  3. FEATURES IMMUNOLOGIC INDICATORS OF CHRONIC TONSILLITIS ASSOCIATED WITH EPSTEIN-BARR VIRUS IN ADULTS

    Directory of Open Access Journals (Sweden)

    Kuchma I.U

    2014-10-01

    Full Text Available Chronic tonsillitis are the most common diseases of the upper respiratory tract. One of the causes of tonsillitis, with severe clinical manifestations or erased is the Epstein - Barr virus (EBV. According to the literature, more than 90% of the adult population infected with EBV and are lifelong carriers of the virus. After primary infection replication of the virus in asymptomatic or in the case of a weakened immune system may develop infectious mononucleosis. Primary EBV infection in adolescence and adults is much greater than in children and often causes the formation of chronic forms. The main entrance gate is EBV oropharyngeal epithelium. In epithelial cells undergoing complete EBV replication with lysis of cells and the formation of a large number of virions. EBV infects B lymphocytes through the interaction of the surface gp320 virus with CD21 (receptor for complement component C3d. In EBV-infected B lymphocytes are two possible kinds of replication: lytic and latent process. During replication of EBV lytic expressed approximately 100 proteins are immunogenic but are 4 types of proteins, which have specific antibodies: early antigen - EA; viral capsid antigen - VCA; Epstein-Barr nuclear antigen - EBNA; latent membrane protein - LMP. LMP-1 induced bcl-2 (a blocker of apoptosis in B-cells and promotes proliferation and migration of B-lymphocytes. Thus, EBV infection is characterized by widespread, reactivation of infection from infected parts that most often manifests itself with recurrent infection with symptoms of chronic tonsillitis. Objective: what features of general and local immunological parameters inherent in chronic tonsillitis in the acute stage, caused by reactivation of EBV infection. Materials and methods. The study included 311 patients with chronic tonsillitis subcompensated in the acute stage. Microbiological testing of samples produced from the throat, determined EBV DNA in saliva, EVB-VCA-IgM, EVB-EA-IgG and EVB-NA-IgG in

  4. Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis.

    Science.gov (United States)

    Tirotta, Emanuele; Duncker, Patrick; Oak, Jean; Klaus, Suzi; Tsukamoto, Michelle R; Gov, Lanny; Lane, Thomas E

    2013-01-15

    Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 and p35 to form the immunomodulatory cytokines IL-27 and IL-35, respectively. Infection of EBI3-/- mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality that was not associated with impaired ability to control viral replication but enhanced T cell and macrophage infiltration into the CNS. IFN-γ secretion from virus-specific CD4+ and CD8+ T cells isolated from infected EBI3-/- mice was augmented while IL-10 expression muted in comparison to infected WT mice. These data demonstrate a regulatory role for EBI3-associated cytokines in controlling host responses following CNS viral infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Sequence analysis of the Epstein-Barr virus (EBV) latent membrane protein-1 gene and promoter region

    DEFF Research Database (Denmark)

    Sandvej, K; Gratama, J W; Munch, M

    1997-01-01

    . The widespread prevalence of LMP-1 sequence variations, particularly the Xho I polymorphism and the 30-bp deletion, indicate that they cannot be used as simple markers for oncogenic viruses related to particular forms of EBV-associated tumor. Several of the structural changes detected occur, however, at sites......Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which...... wild-type virus isolates, we sequenced the LMP-1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D...

  6. Epstein-Barr virus associated modulation of Wnt pathway is not dependent on latent membrane protein-1.

    Directory of Open Access Journals (Sweden)

    Natasha Webb

    2008-09-01

    Full Text Available Previous studies have indicated that Epstein-Barr virus (EBV can modulate the Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded oncogene latent membrane protein 1 (LMP1. Here we have reassessed the role of LMP1 in regulating the expression of various mediators of the canonical Wnt cascade. Contradicting the previous finding, we found that the levels of E-cadherin, beta-catenin, Glycogen Synthase Kinase 3ss (GSK3beta, axin and alpha-catenin were not affected by the expression of LMP1 sequences from normal B cells or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no detectable effect on the E-cadherin and beta-catenin interaction and did not induce transcriptional activation of beta-catenin. Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1.

  7. Prevalence of human papillomavirus and Epstein-Barr virus DNA in Chinese children with tonsillar and/or adenoidal hypertrophy.

    Science.gov (United States)

    Xue, Xiao-cheng; Chen, Xiao-ping; Yao, Wen-hao; Zhang, Yi; Sun, Guang-bin; Tan, Xue-jun

    2014-06-01

    Tonsillar and adenoidal hypertrophy are prevalent otolaryngologic disorders in children, but their pathogenesis is largely unknown. The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNA in 146 tonsil and/or adenoid tissue specimens from 104 Chinese children with tonsillar and/or adenoidal hypertrophy were screened using flow-through hybridization gene-chip technology and real-time fluorescence-based quantitative PCR. Then, the relationships between the prevalence of the viruses and other clinical characteristics of tonsillar and/or adenoidal hypertrophy were analyzed. No patient had HPV DNA. EBV DNA was detected in 19/42 (45.2%) tonsil tissues and 72/104 (69.2%) adenoid tissue specimens (P hypertrophy. Adenoid tissues might more susceptible than tonsil tissues to EBV infection. In addition, EBV infection did not aggravate snoring in patients with tonsillar and/or adenoidal hypertrophy. © 2014 Wiley Periodicals, Inc.

  8. Analysis of Immunogenicity of Intracellular CTAR Fragments of Epstein-Barr Virus Latent Phase Protein LMP1.

    Science.gov (United States)

    Lomakin, Ya A; Shmidt, A A; Bobik, T V; Chernov, A S; Pyrkov, A Yu; Aleksandrova, N M; Okunola, D O; Vaskina, M I; Ponomarenko, N A; Telegin, G B; Dubina, M V; Belogurov, A A

    2017-10-01

    Intracellular fragments of latent phase protein LMP1 of Epstein-Barr virus, denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to the transforming potential of the virus. Generation of recombinant proteins CTAR1/2/3 is expected to yield more ample data on functional and immunogenic characteristics of LMP1. We created genetic constructs for prokaryotic expression of LMP1 CTAR fragments and selected optimal conditions for their production and purification. Using a new library of LMP1 CTAR fragments, we carried out epitope mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of CTAR elements comparable with that of full-length protein.

  9. Co-prevalence of Epstein-Barr virus and high-risk human papillomaviruses in Syrian women with breast cancer.

    Science.gov (United States)

    Al Moustafa, Ala-Eddin; Al-Antary, Noor; Aboulkassim, Tahar; Akil, Nizar; Batist, Gerald; Yasmeen, Amber

    2016-07-02

    ABSTRAT We recently performed 2 studies viewing the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human breast cancer in the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in breast cancer in Syrian women. Therefore, and based on our previous studies and present data, we reveal that 35 (32%) of 108 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high grade invasive ductal carcinomas (IDCs) with at least one positive lymph nodes, in comparison with EBV and high-risk HPVs-positive samples, which are low to intermediate grade IDCs, respectively. Future studies are needed to confirm the co-presence and the cooperation effect of these onco-viruses in human breast carcinogenesis and metastasis.

  10. Mutagenesis and Genome Engineering of Epstein-Barr Virus in Cultured Human Cells by CRISPR/Cas9.

    Science.gov (United States)

    Yuen, Kit-San; Chan, Chi-Ping; Kok, Kin-Hang; Jin, Dong-Yan

    2017-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 nuclease (Cas9) system is a powerful genome-editing tool for both chromosomal and extrachromosomal DNA. DNA viruses such as Epstein-Barr virus (EBV), which undergoes episomal replication in human cells, can be effectively edited by CRISPR/Cas9. We have demonstrated targeted editing of the EBV genome by CRISPR/Cas9 in several lines of EBV-infected cells. CRISPR/Cas9-based mutagenesis and genome engineering of EBV provides a new method for genetic analysis, which has some advantages over bacterial artificial chromosome-based recombineering. This approach might also prove useful in the cure of EBV infection. In this chapter, we use the knockout of the BART promoter as an example to detail the experimental procedures for construction of recombinant EBV in human cells.

  11. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wendy K Glenn

    Full Text Available BACKGROUND: The purpose of this investigation is to determine if Epstein Barr virus (EBV, high risk human papillomavirus (HPV, and mouse mammary tumour viruses (MMTV co-exist in some breast cancers. MATERIALS AND METHODS: All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis and 14 were predominantly invasive ductal carcinomas (idc. RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%, HPV, 20% and MMTV (32% of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. CONCLUSIONS: We conclude that (i EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  12. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Science.gov (United States)

    Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

    2012-01-01

    The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  13. Microbial transformation of isosteviol and inhibitory effects on Epstein-Barr virus activation of the transformation products.

    Science.gov (United States)

    Akihisa, Toshihiro; Hamasaki, Yusuke; Tokuda, Harukuni; Ukiya, Motohiko; Kimura, Yumiko; Nishino, Hoyoku

    2004-03-01

    Microbial transformation of isosteviol (2), a beyerane-type diterpenoid obtained from stevioside (1) by acid hydrolysis, yielded 7beta-hydroxyisosteviol (3), 11beta-hydroxyisosteviol (5), and 12beta-hydroxyisosteviol (6) by the fungus Aspergillus niger, 17-hydroxyisosteviol (7) by the fungus Glomerella cingulata, and 3 and 7-oxoisosteviol (4) by the fungus Mortierella elongate. The five metabolites, 3-7, along with 1 and 2 were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the diterpenes tested showed potent inhibitory effects, with the five metabolites 3-7 exhibiting more potent effects.

  14. Epstein-Barr virus-associated adult respiratory distress syndrome in a patient with AIDS: a case report and review

    DEFF Research Database (Denmark)

    Stopyra, G A; Multhaupt, H A; Alexa, L

    1999-01-01

    such reported case, along with a survey of archival autopsy cases to assess baseline expression of EBV in AIDS patients. DESIGN: The case patient's autopsy material was studied exhaustively for infectious agents by culture, histochemistry, and immunohistochemistry, with negative results. Formalin-fixed paraffin......BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with fatal pneumonitis in immunocompetent patients. We present a case of fatal adult respiratory distress syndrome caused by EBV infection in a patient with acquired immunodeficiency syndrome (AIDS), to our knowledge the first......-embedded lung, spleen, lymph node, and liver tissue were further studied by in situ hybridization using a probe for EBV early RNA (EBER, Kreatech). The same method was applied to lymphoid tissues from eight other archival AIDS autopsy cases. Case patient tissues were also examined by electron microscopy...

  15. Reduced response to Epstein-Barr virus antigens by T-cells in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Draborg, Anette Holck; Jacobsen, Søren; Westergaard, Marie

    2014-01-01

    OBJECTIVE: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. METHODS: T cells were analyzed by flow cytometry and antibodies were...... analyzed by enzyme-linked immunosorbent assay. RESULTS: SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced...... number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV...

  16. A Rare Occurrence of Primary Hepatic Leiomyosarcoma Associated with Epstein Barr Virus Infection in an AIDs Patient

    Directory of Open Access Journals (Sweden)

    Haritha Chelimilla

    2013-01-01

    Full Text Available Primary hepatic leiomyosarcoma is exceedingly rare accounting for less than 1% of the hepatic tumors. Close to 45 cases have been reported in the English literature. Presentation is usually nonspecific and diagnosis is often delayed until tumors reach a large size. This leads to a dismal prognosis. The tumors are not yet fully understood, hence the standard of care is not well defined. Curative resection remains the mainstay of management. Close association of Epstein Barr virus (EBV induced soft tissue sarcomas is proven, especially in the presence of immunosuppression encountered in HIV/AIDS patients and in posttransplant patients. We herein present a case report of a 54-year-old man diagnosed to have HIV/AIDS and EBV infection admitted to our hospital with complaints of intractable hiccups for more than a week. Extensive workup revealed primary leiomyosarcoma of the liver.

  17. Epstein-Barr virus super-enhancer eRNAs are essential for MYC oncogene expression and lymphoblast proliferation.

    Science.gov (United States)

    Liang, Jun; Zhou, Hufeng; Gerdt, Catherine; Tan, Min; Colson, Tyler; Kaye, Kenneth M; Kieff, Elliott; Zhao, Bo

    2016-12-06

    Epstein-Barr virus (EBV) super-enhancers (ESEs) are essential for lymphoblastoid cell (LCL) growth and survival. Reanalyses of LCL global run-on sequencing (Gro-seq) data found abundant enhancer RNAs (eRNAs) being transcribed at ESEs. Inactivation of ESE components, EBV nuclear antigen 2 (EBNA2) and bromodomain-containing protein 4 (BRD4), significantly decreased eRNAs at ESEs -428 and -525 kb upstream of the MYC oncogene transcription start site (TSS). shRNA knockdown of the MYC -428 and -525 ESE eRNA caused LCL growth arrest and reduced cell growth. Furthermore, MYC ESE eRNA knockdown also significantly reduced MYC expression, ESE H3K27ac signals, and MYC ESEs looping to MYC TSS. These data indicate that ESE eRNAs strongly affect cell gene expression and enable LCL growth.

  18. Epstein-Barr virus-associated adult respiratory distress syndrome in a patient with AIDS: a case report and review

    DEFF Research Database (Denmark)

    Stopyra, G A; Multhaupt, H A; Alexa, L

    1999-01-01

    -embedded lung, spleen, lymph node, and liver tissue were further studied by in situ hybridization using a probe for EBV early RNA (EBER, Kreatech). The same method was applied to lymphoid tissues from eight other archival AIDS autopsy cases. Case patient tissues were also examined by electron microscopy......BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with fatal pneumonitis in immunocompetent patients. We present a case of fatal adult respiratory distress syndrome caused by EBV infection in a patient with acquired immunodeficiency syndrome (AIDS), to our knowledge the first...... and pneumocytes. Of the archival cases studied, only one spleen was found to have rare positive lymphocytes. CONCLUSION: Primary or reactivation EBV infection may represent a previously underreported cause of morbidity and mortality in AIDS patients. Autopsy tissues from AIDS patients do not routinely show...

  19. Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency

    DEFF Research Database (Denmark)

    Abolhassani, Hassan; Edwards, Emily S. J.; Ikinciogullari, Aydan

    2017-01-01

    is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70-CD27 interactions therefore play a nonredundant role in T and B cell-mediated immunity, especially for protection against EBV and humoral immunity.......In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)-related diseases. Three patients presented with EBV-associated Hodgkin's lymphoma...... and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal...

  20. Cell surface alteration in Epstein-Barr virus-transformed cells from patients with extreme insulin resistance

    International Nuclear Information System (INIS)

    Gorden, D.L.; Robert, A.; Moncada, V.Y.; Taylor, S.I.; Muehlhauser, J.C.; Carpentier, J.L.

    1990-01-01

    An abnormality was detected in the morphology of the cell surface of Epstein-Barr virus-transformed lymphocytes of patients with genetic forms of insulin resistance. In cells from two patients with leprechaunism and two patients with type A extreme insulin resistance, scanning electron microscopy demonstrated a decrease in the percentage of the cell surface occupied by microvilli in cells from the patients with leprechaunism and type A insulin resistance compared with control cells. When cells from a healthy control subject and one of the patients with leprechaunism (Lep/Ark-1) were incubated with 125 I-labeled insulin, there was a decrease in the percentage of 125 I-insulin associated with microvilli on the cell surface. Thus, the decreased localization of insulin receptors with the microvillous region of the cell surface was in proportion to the decrease in microvilli

  1. The Epstein-Barr Virus BART miRNA Cluster of the M81 Strain Modulates Multiple Functions in Primary B Cells

    Science.gov (United States)

    Lin, Xiaochen; Tsai, Ming-Han; Shumilov, Anatoliy; Poirey, Remy; Bannert, Helmut; Middeldorp, Jaap M.; Feederle, Regina; Delecluse, Henri-Jacques

    2015-01-01

    The Epstein-Barr virus (EBV) is a B lymphotropic virus that infects the majority of the human population. All EBV strains transform B lymphocytes, but some strains, such as M81, also induce spontaneous virus replication. EBV encodes 22 microRNAs (miRNAs) that form a cluster within the BART region of the virus and have been previously been found to stimulate tumor cell growth. Here we describe their functions in B cells infected by M81. We found that the BART miRNAs are downregulated in replicating cells, and that exposure of B cells in vitro or in vivo in humanized mice to a BART miRNA knockout virus resulted in an increased proportion of spontaneously replicating cells, relative to wild type virus. The BART miRNAs subcluster 1, and to a lesser extent subcluster 2, prevented expression of BZLF1, the key protein for initiation of lytic replication. Thus, multiple BART miRNAs cooperate to repress lytic replication. The BART miRNAs also downregulated pro- and anti-apoptotic mediators such as caspase 3 and LMP1, and their deletion did not sensitize B-cells to apoptosis. To the contrary, the majority of humanized mice infected with the BART miRNA knockout mutant developed tumors more rapidly, probably due to enhanced LMP1 expression, although deletion of the BART miRNAs did not modify the virus transforming abilities in vitro. This ability to slow cell growth could be confirmed in non-humanized immunocompromized mice. Injection of resting B cells exposed to a virus that lacks the BART miRNAs resulted in accelerated tumor growth, relative to wild type controls. Therefore, we found that the M81 BART miRNAs do not enhance B-cell tumorigenesis but rather repress it. The repressive effects of the BART miRNAs on potentially pathogenic viral functions in infected B cells are likely to facilitate long-term persistence of the virus in the infected host. PMID:26694854

  2. Glypican-4 gene polymorphism (rs1048369) and susceptibility to Epstein-Barr virus-associated and -negative gastric carcinoma.

    Science.gov (United States)

    Zhao, Danrui; Liu, Shuzhen; Sun, Lingling; Zhao, Zhenzhen; Liu, Song; Kuang, Xiaojing; Shu, Jun; Luo, Bing

    2016-07-15

    Gastric cancer (GC) is one of the most common malignant tumors in China and single nucleotide polymorphisms (SNPs) have been found to be highly related to GC carcinogenesis. Glypican-4 (GPC4), a member of the heparan sulphate proteoglycan family, plays an important role in the regulation of cell growth and differentiation. However, little is known about polymorphisms of GPC4 gene and their associated susceptibility to GC, especially to Epstein-Barr virus-associated GC (EBVaGC). Here we studied the GPC4 polymorphism (rs1048369) in GC individuals, especially those with EBVaGC, and we explored an association between the GPC4 gene polymorphism (rs1048369) and susceptibility to EBVaGC and Epstein-Barr virus-negative GC (EBVnGC) in a population from Northern China. The GPC4 gene polymorphism (rs1048369) was detected in 54 cases of EBVaGC and 73 cases of EBVnGC using polymerase chain reaction (PCR). One hundred and seven peripheral blood samples from healthy individuals were also measured as a control group. There were significant differences in both the genotype and allelic frequency of GPC4 gene (rs1048369) between the EBVaGC and EBVnGC patients. Meanwhile, the distribution of genotype and allelic frequency of GPC4 (rs1048369) differed between EBVaGC and control groups. Distribution of the GPC4 genotype also revealed differences between EBVnGC and control groups, no significant differences in the allelic frequency of the GPC4 gene (rs1048369) were observed. The frequency of the T allele in EBVaGC group was significantly higher than that in control and EBVnGC groups. The GPC4 gene polymorphism and the allele of GPC4 are both associated with susceptibility to EBVaGC. The T allele of GPC4 may represent a risk factor for EBVaGC. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

    Science.gov (United States)

    Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

    2016-01-01

    ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

  4. Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus.

    Science.gov (United States)

    Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J; King, Sarah L; Vakhrushev, Sergey Y; Olofsson, Sigvard; Wandall, Hans H

    2016-06-03

    Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a "bottom up" mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus*

    Science.gov (United States)

    Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J.; King, Sarah L.; Vakhrushev, Sergey Y.; Olofsson, Sigvard; Wandall, Hans H.

    2016-01-01

    Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a “bottom up” mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation. PMID:27129252

  6. The Definition of Epstein Barr Virus (EBV)’s Role in HTLV-III Infected USAF Personnel as Related to Disease Progression

    Science.gov (United States)

    1989-04-15

    manifestations. The subgroup of patients with oral hairy leukoplakia (OIIL) had an overall high body burden of EBV, including a high density of (ntinued on...result of the increased longevity of HIV-infected patients through the administration of antiretroviral chemotherapy. Oral hairy leukoplakia was found...Boswell RN: Erhanced Epstein-Barr virus activity in patients with oral hairy leukoplakia and human iMndeficiency virus infection. Presented at the

  7. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    Science.gov (United States)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  8. Low intrathecal antibody production despite high seroprevalence of Epstein-Barr virus in multiple sclerosis: a review of the literature.

    Science.gov (United States)

    Ruprecht, Klemens; Wildemann, Brigitte; Jarius, Sven

    2018-02-01

    Patients with multiple sclerosis (MS) frequently have an intrathecal production of antibodies to different common viruses, which can be detected by elevated antiviral antibody indices (AIs). There is a strong and consistent association of MS and Epstein-Barr virus (EBV) infection. To systematically compare the frequencies of intrathecal antibody production to EBV, measles virus, rubella virus, varicella zoster virus (VZV) and herpes simplex virus (HSV) in patients with MS. Review of the English and German literature on the frequencies of intrathecal immunoglobulin (Ig)G antibody production, as defined by an elevated AI, to EBV, measles virus, rubella virus, VZV and HSV in adult and pediatric patients with MS. In nine original studies identified, the frequencies of an intrathecal production of antibodies to Epstein-Barr nuclear antigen-1 (33/340, 9.7%), EBV viral capsid antigen (12/279, 4.3%) and antigens from EBV-infected cell lines (14/90, 15.6%) in adult patients with MS were clearly lower (p ≤ 0.03 for all pairwise comparisons) than the frequencies of an intrathecal production of antibodies to measles virus (612/922, 66.4%), rubella virus (521/922, 56.5%), VZV (470/922, 51%; data from 17 original studies) and HSV (78/291, 26.8%; data from 6 original studies). Though based on a lower number of original studies and patients, findings in children with MS were essentially similar. As in adults and children with MS the seroprevalence of EBV is higher than the seroprevalences of the other investigated viruses, the lower frequency of elevated EBV AIs became even more pronounced after correction of the frequencies of elevated antiviral AIs for the seroprevalences of the respective viruses. Given the very high seroprevalence of EBV in MS, the frequency of intrathecally produced antibodies to EBV in patients with MS is paradoxically low compared to that of other common viruses. These findings are compatible with the recently proposed hypothesis that in individuals

  9. Structure of Epstein-Barr Virus Glycoprotein 42 Suggests a Mechanism for Triggering Receptor-Activated Virus Entry

    Energy Technology Data Exchange (ETDEWEB)

    Kirschner, Austin N.; Sorem, Jessica; Longnecker, Richard; Jardetzky, Theodore S.; (NWU); (Stanford-MED)

    2009-05-26

    Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLA complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an {alpha} helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.

  10. Association of Monoclonal Expansion of Epstein-Barr Virus-Negative CD158a+ NK Cells Secreting Large Amounts of Gamma Interferon with Hemophagocytic Lymphohistiocytosis▿

    Science.gov (United States)

    López-Álvarez, María R.; Martínez-Sánchez, María V.; Salgado-Cecilia, María G.; Campillo, José A.; Heine-Suñer, Damian; Villar-Permuy, Florentina; Fuster, José L.; Bas, Águeda; Gil-Herrera, Juana; Muro, Manuel; García-Alonso, Ana M.; Álvarez-López, María R.; Minguela, Alfredo

    2009-01-01

    We report the first case of hemophagocytic lymphohistiocytosis (HLH) induced by the monoclonal expansion of Epstein-Barr virus (EBV)-negative NK cells. Consanguinity of the patient's parents made it necessary to discard familial HLH in the patient and her sister with identical HLA markers and demonstrate that no cause other than the expansion of NK cells, which secrete high levels of gamma interferon, was inducing HLH in this patient. PMID:19020108

  11. Central nervous system involvement in Hodgkin's lymphoma associated with Epstein-Barr virus in a patient with AIDS: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    Full Text Available Intracranial and intraspinal involvement is a rare complication of Hodgkin's disease. We report a case of a patient with diagnosis of AIDS and Hodgkin's lymphoma who developed brain and spinal involvement at the time of the relapse of the neoplasm disease. Mixed cellularity histology was the subtype of Hodgkin's disease in our patient; we identified the Epstein-Barr virus genome in the Reed-Sternberg cells by immunohistochemistry and in situ hybridization.

  12. Analysis of the Variability of Epstein-Barr Virus Genes in Infectious Mononucleosis: Investigation of the Potential Correlation with Biochemical Parameters of Hepatic Involvement

    Directory of Open Access Journals (Sweden)

    Banko Ana

    2016-09-01

    Full Text Available Background: Primary Epstein-Barr virus (EBV infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM, during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters.

  13. PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model

    OpenAIRE

    Ma, Shi-Dong; Xu, Xuequn; Jones, Richard; Delecluse, Henri-Jacques; Zumwalde, Nicholas A.; Sharma, Akshat; Gumperz, Jenny E.; Kenney, Shannon C.

    2016-01-01

    Epstein-Barr virus (EBV) infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperit...

  14. Pembrolizumab, Capecitabine, and Radiation Therapy in Treating Patients With Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer

    Science.gov (United States)

    2017-11-15

    Epstein-Barr Virus Positive; Gastric Adenocarcinoma; Mismatch Repair Protein Deficiency; Stage IB Gastric Cancer AJCC v7; Stage II Gastric Cancer AJCC v7; Stage IIA Gastric Cancer AJCC v7; Stage IIB Gastric Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7

  15. Comparison of QIAsymphony Automated and QIAamp Manual DNA Extraction Systems for Measuring Epstein-Barr Virus DNA Load in Whole Blood Using Real-Time PCR

    OpenAIRE

    Laus, Stella; Kingsley, Lawrence A.; Green, Michael; Wadowsky, Robert M.

    2011-01-01

    Automated and manual extraction systems have been used with real-time PCR for quantification of Epstein-Barr virus [human herpesvirus 4 (HHV-4)] DNA in whole blood, but few studies have evaluated relative performances. In the present study, the automated QIAsymphony and manual QIAamp extraction systems (Qiagen, Valencia, CA) were assessed using paired aliquots derived from clinical whole-blood specimens and an in-house, real-time PCR assay. The detection limits using the QIAsymphony and QIAam...

  16. Inhibition of Antigen Presentation by the Glycine/Alanine Repeat Domain Is Not Conserved in Simian Homologues of Epstein-Barr Virus Nuclear Antigen 1

    OpenAIRE

    Blake, Neil W.; Moghaddam, Amir; Rao, Pasupuleti; Kaur, Amitinder; Glickman, Rhona; Cho, Young-gyu; Marchini, Andrew; Haigh, Tracey; Johnson, R. Paul; Rickinson, Alan B.; Wang, Fred

    1999-01-01

    Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptovirus (LCV) subgroup. Several potential strategies for immune evasion and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experimentally. Interest has focused on the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and re...

  17. Investigation of BK virus, Epstein-Barr virus and human papillomavirus sequences in postoperative thyroid gland specimens.

    Science.gov (United States)

    Stamatiou, Dimitris; Derdas, Stavros P; Symvoulakis, Emmanouil K; Sakorafas, Georgios H; Zoras, Odysseas; Spandidos, Demetrios A

    2015-02-24

    Although recent evidence has implicated viruses in the regulation of epithelial-to-mesenchymal transition and tumor progression, little is known regarding viral infections in thyroid malignancies. Thus the aim of this study was to detect sequences of 3 potentially oncogenic viruses - BK virus (BKV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) - in a series of postoperative thyroid gland specimens. Thirty patients with thyroid nodules who underwent surgery for thyroid disease within a 3-year period were enrolled. Both nodular and adjacent normal thyroid tissue was surgically excised from each patient. Viral gene sequences of BKV (VP1), EBV (LMP1, EBNA2 and EBER1) and HPV were amplified by PCR. The PCR results were confirmed by direct sequencing analysis. VP1 gene sequences were detected in 60% (18/30) of thyroid cancer or multinodular hyperplasia lesions compared with in 43.3% (13/30) of adjacent normal thyroid tissue specimens. Fifteen of thirty (50%) of thyroid cancer or multinodular hyperplasia samples revealed LMP1 sequences compared with 46.7% (14/30) of corresponding normal thyroid tissues. EBNA2 gene sequences were detected in 90% (27/30) of thyroid cancer or multinodular hyperplasia samples, compared with 90% (27/30) of adjacent normal thyroid tissue specimens. All samples were negative for EBER1 sequences, while HPV DNA was not detected in either nodular or normal thyroid tissue. This study suggests that BKV and EBV "infection" is an early event, occurring within normal tissue. Our findings do not show a clear role for the viruses examined, instead they suggest an "endemicity" pattern rather than a causal effect.

  18. Seroprevalence of cytomegalovirus, Epstein Barr virus and varicella zoster virus among pregnant women in Bradford: a cohort study.

    Directory of Open Access Journals (Sweden)

    Lucy Pembrey

    Full Text Available To estimate the seroprevalence of cytomegalovirus (CMV, Epstein Barr virus (EBV and varicella zoster virus (VZV among pregnant women in Bradford by ethnic group and country of birth.A stratified random sample of 949 pregnant women enrolled in the Born in Bradford birth cohort was selected to ensure sufficient numbers of White UK born women, Asian UK born women and Asian women born in Asia. Serum samples taken at 24-28 weeks' gestation were tested for CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included socio-demographic information.CMV seroprevalence was 49% among the White British women, 89% among South Asian UK born women and 98% among South Asian women born in South Asia. These differences remained after adjusting for socio-demographic factors. In contrast, VZV seroprevalence was 95% among women born in the UK but significantly lower at 90% among South Asian women born in Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country of birth.Although about half of White British women are at risk of primary CMV infection in pregnancy and the associated increased risk of congenital infection, most congenital CMV infections are likely to be in children born to South Asian women with non-primary infection during pregnancy. South Asian women born in South Asia are at risk of VZV infection during pregnancy which could produce congenital varicella syndrome or perinatal chickenpox. Differences in CMV and VZV seroprevalence by ethnic group and country of birth must be taken into account when universal immunisation against these viruses is contemplated.

  19. Epstein-Barr Virus-Associated Gastric Carcinoma: Use of Host Cell Machineries and Somatic Gene Mutations.

    Science.gov (United States)

    Abe, Hiroyuki; Kaneda, Atsushi; Fukayama, Masashi

    2015-01-01

    Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric carcinoma, consisting of clonal growth of EBV-infected epithelial cells. Its unique characteristics have been demonstrated by epidemiological, clinical and pathological studies using in situ hybridization for EBV-encoded small RNAs. An oncogenic process for EBVaGC has also been revealed. EBV uses various host-cell machineries, including cell division machinery to propagate clonal virus genomes, DNA-methylation machinery to epigenetically control infected cells, and microRNA and exosome machineries to modify the behavior and microenvironment of infected cells. Recent comprehensive molecular analyses from The Cancer Genome Atlas project demonstrate that EBVaGC is a representative molecular subtype that is distinct from microsatellite unstable, genomically stable and chromosome unstable subtypes. In addition to having the highest level of DNA methylation in CpG islands of promoter regions, EBVaGC harbors particular gene alterations, including a high frequency of mutations in PIK3CA and ARID1A, mutation in BCOR, and amplification of PD-L1 and PD-L2. Although currently undetermined, the virus might use the altered cellular functions that are induced by these somatic mutations. Further investigation of virus-driven oncogenesis will enable hitherto unknown functions of stomach epithelial cell machineries to be elucidated, which may reveal potential therapeutic targets for EBVaGC. © 2015 S. Karger AG, Basel.

  20. Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients With Refractory Celiac Disease.

    Science.gov (United States)

    Perfetti, Vittorio; Baldanti, Fausto; Lenti, Marco Vincenzo; Vanoli, Alessandro; Biagi, Federico; Gatti, Marta; Riboni, Roberta; Dallera, Elena; Paulli, Marco; Pedrazzoli, Paolo; Corazza, Gino Roberto

    2016-08-01

    Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein-Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of latency- and replication-associated proteins confirmed active infection. Further studies are needed to determine whether EBV infection contributes to the pathogenesis of refractory celiac disease and enteropathy-associated T-cell lymphoma. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Structural and Functional Basis for an EBNA1 Hexameric Ring in Epstein-Barr Virus Episome Maintenance.

    Science.gov (United States)

    Deakyne, Julianna S; Malecka, Kimberly A; Messick, Troy E; Lieberman, Paul M

    2017-10-01

    Epstein-Barr virus (EBV) establishes a stable latent infection that can persist for the life of the host. EBNA1 is required for the replication, maintenance, and segregation of the latent episome, but the structural features of EBNA1 that confer each of these functions are not completely understood. Here, we have solved the X-ray crystal structure of an EBNA1 DNA-binding domain (DBD) and discovered a novel hexameric ring oligomeric form. The oligomeric interface pivoted around residue T585 as a joint that links and stabilizes higher-order EBNA1 complexes. Substitution mutations around the interface destabilized higher-order complex formation and altered the cooperative DNA-binding properties of EBNA1. Mutations had both positive and negative effects on EBNA1-dependent DNA replication and episome maintenance with OriP. We found that one naturally occurring polymorphism in the oligomer interface (T585P) had greater cooperative DNA binding in vitro , minor defects in DNA replication, and pronounced defects in episome maintenance. The T585P mutant was compromised for binding to OriP in vivo as well as for assembling the origin recognition complex subunit 2 (ORC2) and trimethylated histone 3 lysine 4 (H3K4me3) at OriP. The T585P mutant was also compromised for forming stable subnuclear foci in living cells. These findings reveal a novel oligomeric structure of EBNA1 with an interface subject to naturally occurring polymorphisms that modulate EBNA1 functional properties. We propose that EBNA1 dimers can assemble into higher-order oligomeric structures important for diverse functions of EBNA1. IMPORTANCE Epstein-Barr virus is a human gammaherpesvirus that is causally associated with various cancers. Carcinogenic properties are linked to the ability of the virus to persist in the latent form for the lifetime of the host. EBNA1 is a sequence-specific DNA-binding protein that is consistently expressed in EBV tumors and is the only viral protein required to maintain the viral

  2. An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1.

    Science.gov (United States)

    Skinner, Camille M; Ivanov, Nikita S; Barr, Sarah A; Chen, Yan; Skalsky, Rebecca L

    2017-11-01

    Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3' untranslated region (UTR) by EBV miR-BHRF1-2-5p was confirmed using 3'-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis. IMPORTANCE IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell. Copyright © 2017 American Society for Microbiology.

  3. Genome-Wide Analysis of 18 Epstein-Barr Viruses Isolated from Primary Nasopharyngeal Carcinoma Biopsy Specimens.

    Science.gov (United States)

    Tu, Chaofeng; Zeng, Zhaoyang; Qi, Peng; Li, Xiayu; Yu, Zhengyuan; Guo, Can; Xiong, Fang; Xiang, Bo; Zhou, Ming; Gong, Zhaojian; Liao, Qianjin; Yu, Jianjun; He, Yi; Zhang, Wenling; Li, Xiaoling; Li, Yong; Li, Guiyuan; Xiong, Wei

    2017-09-01

    Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that is highly prevalent in almost all human populations and is associated with many human cancers, such as nasopharyngeal carcinoma (NPC), Hodgkin's disease, and gastric carcinoma. However, in these EBV-associated cancers, only NPC exhibits remarkable ethnic and geographic distribution. We hypothesized that EBV genomic variations might contribute to the pathogenesis of different human cancers in different geographic areas. In this study, we collected 18 NPC biopsy specimens from the Hunan Province in southern China and de novo assembled 18 NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HN1 to HN18. This was achieved through target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, to reveal sequence diversity. These EBV genomes harbored 20,570 variations totally, including 20,328 substitutions, 88 insertions, and 154 deletions, compared to the EBV reference genome. Phylogenetic analysis revealed that all NPC-EBV genomes were distinct from other EBV genomes. Furthermore, HN1 to HN18 had some nonsynonymous variations in EBV genes including genes encoding latent, early lytic, and tegument proteins, such as substitutions within transmembrane domains 1 and 3 of LMP1, FoP_duplication, and zf-AD domains of ENBA1, in addition to aberrations in noncoding regions, especially in BamHI A rightward transcript microRNAs. These variations might have potential biological significance. In conclusion, we reported a genome-wide view of sequence variation in EBV isolated from primary NPC biopsy specimens obtained from the Hunan Province. This might contribute to further understanding of how genomic variations contribute to carcinogenesis, which would impact the treatment of EBV-associated cancer. IMPORTANCE Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV) infection and exhibits remarkable ethnic and geographic distribution. Hunan Province in southern

  4. How compelling are the data for Epstein-Barr virus being a trigger for systemic lupus and other autoimmune diseases?

    Science.gov (United States)

    Draborg, Anette; Izarzugaza, Jose M G; Houen, Gunnar

    2016-07-01

    Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on EBV, and present our integrated theory of SLE development. SLE patients have dysfunctional control of EBV infection resulting in frequent reactivations and disease progression. These comprise impaired functions of EBV-specific T-cells with an inverse correlation to disease activity and elevated serum levels of antibodies against lytic cycle EBV antigens. The presence of EBV proteins in renal tissue from SLE patients with nephritis suggests direct involvement of EBV in SLE development. As expected for patients with immunodeficiencies, studies reveal that SLE patients show dysfunctional responses to other viruses as well. An association with EBV infection has also been demonstrated for other autoimmune diseases, including Sjögren's syndrome, rheumatoid arthritis, and multiple sclerosis. Collectively, the interplay between an impaired immune system and the cumulative effects of EBV and other viruses results in frequent reactivation of EBV and enhanced cell death, causing development of SLE and concomitant autoreactivities.

  5. Comparison of two automated instruments for Epstein-Barr virus serology in a large adult hospital and implementation of an Epstein-Barr virus nuclear antigen-based testing algorithm.

    Science.gov (United States)

    Al Sidairi, Hilal; Binkhamis, Khalifa; Jackson, Colleen; Roberts, Catherine; Heinstein, Charles; MacDonald, Jimmy; Needle, Robert; Hatchette, Todd F; LeBlanc, Jason J

    2017-11-01

    Serology remains the mainstay for diagnosis of Epstein-Barr virus (EBV) infection. This study compared two automated platforms (BioPlex 2200 and Architect i2000SR) to test three EBV serological markers: viral capsid antigen (VCA) immunoglobulins of class M (IgM), VCA immunoglobulins of class G (IgG) and EBV nuclear antigen-1 (EBNA-1) IgG. Using sera from 65 patients at various stages of EBV disease, BioPlex demonstrated near-perfect agreement for all EBV markers compared to a consensus reference. The agreement for Architect was near-perfect for VCA IgG and EBNA-1 IgG, and substantial for VCA IgM despite five equivocal results. Since the majority of testing in our hospital was from adults with EBNA-1 IgG positive results, post-implementation analysis of an EBNA-based algorithm showed advantages over parallel testing of the three serologic markers. This small verification demonstrated that both automated systems for EBV serology had good performance for all EBV markers, and an EBNA-based testing algorithm is ideal for an adult hospital.

  6. Close relationship between immunoglobulin secreting-cells and Epstein-Barr virus reservoir in patients infected with HIV.

    Science.gov (United States)

    Ouedraogo, David Eric; Tuaillon, Edouard; Rubbo, Pierre-Alain; Bollore, Karine; Foulongne, Vincent; Reynes, Jacques; Vendrell, Jean-Pierre

    2014-01-01

    Individuals infected with HIV have higher circulating Epstein-Barr virus (EBV) DNA load compared to healthy carriers. This study investigated whether level of spontaneous immunoglobulin secreting cells, one of the major hallmarks of HIV infection, is associated with an increase of EBV DNA load in PBMCs and the spontaneous EBV lytic cycle ex vivo in patients infected with HIV. Spontaneous virus production by cells infected with EBV and EBV DNA loads in PBMCs from which CD8(+) T-cells were removed were measured in 20 HIV-aviremic and 14 HIV-viremic patients. The number of circulating immunoglobulin-secreting cells (Ig-SCs) and CD8(+) T-lymphocyte activation were also investigated. Patients with detectable HIV RNA in plasma exhibited higher spontaneous ex vivo EBV secretion and higher levels of EBV DNA in PBMCs than their aviremic counterparts. In the two groups observed, a positive correlation was found between PBMCs EBV DNA viral load and Ig-SCs, CD38(bright) expression on CD8(+) T-cells and EBV DNA load in cell culture supernatants. These findings suggest that B-cell polyclonal activation and B-cell terminal differentiation into Ig-SCs may fuel EBV DNA reservoir and promote EBV production ex vivo in patients infected with HIV. © 2013 Wiley Periodicals, Inc.

  7. Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease

    Directory of Open Access Journals (Sweden)

    Paibel Aguayo-Hiraldo

    2016-01-01

    Full Text Available Fifty years after the first reports of Epstein-Barr virus (EBV-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease. This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.

  8. Transplantation of solid organ recipients shedding Epstein-Barr virus DNA pre-transplant: A prospective study.

    Science.gov (United States)

    Verghese, Priya S; Schmeling, David O; Filtz, Emma A; Grimm, Jennifer M; Matas, Arthur J; Balfour, Henry H

    2017-11-01

    Epstein-Barr virus (EBV) poses a significant threat to patient and graft survival post-transplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease post-transplant. To test this hypothesis, we conducted a 5-year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years. Pre-transplant samples were available from 98 subjects. EBV DNA was detected pre-transplant in 32 of 95 (34%) and 5 of 93 subjects (5%) in oral wash and blood, respectively. Recipients with and without detectable pre-transplant EBV DNA were not significantly different demographically and had no significant difference in patient and graft survival (P = .6 for both comparisons) or post-transplant EBV viremia-free survival (P = .8). There were no cases of EBV-related disease or post-transplant lymphoproliferative disorder (PTLD) in any of the patients with detectable EBV DNA pre-transplant. In conclusion, detectable EBV DNA pre-transplant was not associated with differences in patient/graft survival, post-transplant EBV viremia, or EBV-related diseases including PTLD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Evaluation of the presence of Epstein-Barr virus (EBV) in Iranian patients with thyroid papillary carcinoma.

    Science.gov (United States)

    Homayouni, Maryam; Mohammad Arabzadeh, Seyed Ali; Nili, Fatemeh; Razi, Farideh; Amoli, Mahsa Mohammad

    2017-07-01

    Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma. In this study the presence of Epstein-Barr Nuclear Antigen 1 (EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N=41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene. In 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages. The significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.

    Science.gov (United States)

    Price, Alexander M; Dai, Joanne; Bazot, Quentin; Patel, Luv; Nikitin, Pavel A; Djavadian, Reza; Winter, Peter S; Salinas, Cristina A; Barry, Ashley Perkins; Wood, Kris C; Johannsen, Eric C; Letai, Anthony; Allday, Martin J; Luftig, Micah A

    2017-04-20

    Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFκB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFκB early after infection. We used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL-1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival mechanisms is unique to virus-infected cells and relies on regulation of MCL-1 mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein. This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis.

  11. Rapid CRISPR/Cas9-Mediated Cloning of Full-Length Epstein-Barr Virus Genomes from Latently Infected Cells.

    Science.gov (United States)

    Yajima, Misako; Ikuta, Kazufumi; Kanda, Teru

    2018-04-03

    Herpesviruses have relatively large DNA genomes of more than 150 kb that are difficult to clone and sequence. Bacterial artificial chromosome (BAC) cloning of herpesvirus genomes is a powerful technique that greatly facilitates whole viral genome sequencing as well as functional characterization of reconstituted viruses. We describe recently invented technologies for rapid BAC cloning of herpesvirus genomes using CRISPR/Cas9-mediated homology-directed repair. We focus on recent BAC cloning techniques of Epstein-Barr virus (EBV) genomes and discuss the possible advantages of a CRISPR/Cas9-mediated strategy comparatively with precedent EBV-BAC cloning strategies. We also describe the design decisions of this technology as well as possible pitfalls and points to be improved in the future. The obtained EBV-BAC clones are subjected to long-read sequencing analysis to determine complete EBV genome sequence including repetitive regions. Rapid cloning and sequence determination of various EBV strains will greatly contribute to the understanding of their global geographical distribution. This technology can also be used to clone disease-associated EBV strains and test the hypothesis that they have special features that distinguish them from strains that infect asymptomatically.

  12. Distribution and characterization of environmental promoter substances as assayed by synergistic Epstein-Barr virus-activating system.

    Science.gov (United States)

    Ito, Y; Tokuda, H; Ohigashi, H; Koshimizu, K

    1983-01-01

    The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and tumor-promoting diterpene esters enabled rapid and easy detection of environmental substances with Epstein-Barr virus (EBV)-activating/tumor-promoting potency. Over 500 samples were tested and more than 30 substances with such activities were identified. Most, if not all, were plant diterpene esters derived from Euphorbiaceae and Thymelaeaceae families and a few were indole alkaloids of microbial origin. We attempted to link these laboratory findings with those of epidemiological field studies on three virus-associated diseases, Burkitt's lymphoma, nasopharyngeal carcinoma, and adult T-cell leukemia/lymphoma, which are known to have a peculiar geographical distribution. Our hypothesis was that EBV-activating/tumor-promoting substances might be present in the abundant areas where such diseases are endemic. We noticed that many active diterpene ester-containing plants are widely used as herbal medicaments in Africa and China and determined many plant species that had such activities. One example is Aleurites fordii, a plant commonly grown in Southern China for industrial purposes which yielded a potent promoter substance (12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate, HHPA). The active diterpene esters were purified and their possible mechanism was studied from the view of receptor-binding, protein kinase C activation and transmembrane signaling.

  13. Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

    Science.gov (United States)

    O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2002-01-01

    Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.

  14. Detection of the Epstein-Barr virus, Human Bocavirus and novel KI and KU polyomaviruses in adenotonsillar tissues.

    Science.gov (United States)

    Günel, Ceren; Kırdar, Sevin; Ömürlü, İmran Kurt; Ağdaş, Fatih

    2015-03-01

    We aimed to investigate the seasonal disturbations and the rates of detection of Epstein-Barr virus (EBV), Human Bocavirus (HBoV), and polyomaviruses KI and WU (KIPyV and WUPyV) in adenoid and tonsil tissues during the absence of acute infection symptoms. Cross-sectional prospective study. Tertiary hospital. DNA expressions of EBV, HBoV, polyomaviruses KIPyV and WUPyV were investigated in children with chronic tonsillar and adenoidal diseases using real-time polymerase chain reaction. The patients were grouped as follows: adenoid, recurrent tonsillitis and hypertrophic tonsillitis group. The relationships of the expressions of these viruses with age, gender, recurrent infection and airway obstruction were also analyzed. Seasonal variations in rates of detection of these viruses in adenoid and tonsil tissues were also investigated. Considering adenoid specimens, HBoV was found to be the most frequent virus with the rate of 43.1%. In specimens of recurrent tonsillitis and hypertrophic tonsils, EBV was the most frequently encountered virus (53.8%, and 32.0%, respectively). In children with hypertrophic adenoids, while HBoV was detected to be positive throughout the year, EBV was present throughout the year in children with recurrent tonsillitis. The detection of HBoV and EBV throughout the year in samples of children with asymptomatic chronic adenotonsillar diseases may indicate that these viruses may remain persistently in lymphoepithelial tissues of upper respiratory tract. Virus persistence may have a pathogenetic potential for development of lymphoid hypertrophy and a chronic stimulatory effect for inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced gene 2 (GPR183)

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Norn, Christoffer; Laurent, Stephane

    2012-01-01

    , the family of G protein-coupled seven transmembrane-spanning receptors (7TM receptors) was added to this group. Specifically, the Epstein-Barr virus-induced gene 2 (EBI2 or GPR183) was shown to be activated by several oxysterols, most potently by 7α,25-dihydroxycholesterol (7α,25-OHC). Nothing is known about...... the binding mode, however. Using mutational analysis, we identify here four key residues for 7α,25-OHC binding: Arg-87 in TM-II (position II:20/2.60), Tyr-112 and Tyr-116 (positions III:09/3.33 and III:13/3.37) in TM-III, and Tyr-260 in TM-VI (position VI:16/6.51). Substituting these residues with Ala and....../or Phe results in a severe decrease in agonist binding and receptor activation. Docking simulations suggest that Tyr-116 interacts with the 3β-OH group in the agonist, Tyr-260 with the 7α-OH group, and Arg-87, either directly or indirectly, with the 25-OH group, although nearby residues likely also...

  16. Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

    Science.gov (United States)

    Mameli, Giuseppe; Cocco, Eleonora; Frau, Jessica; Arru, Giannina; Caggiu, Elisa; Marrosu, Maria Giovanna; Sechi, Leonardo A

    2016-07-07

    Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

  17. Epstein-Barr virus as a possible etiologic agent in primary central nervous system lymphoma in immunocompetent individuals.

    Science.gov (United States)

    Tandon, Ashwani; Challa, Sundaram; Shanmugam, M; Gopalan, Swarnalatha; Paul, Roshni T; Digumarthi, Raghunadharao

    2009-01-01

    Primary central nervous system lymphoma (PCNSL) occurs in both immunocompetent and immunosuppressed individuals. The role of Epstein-Barr virus (EBV) has been implicated in immunosuppressed individuals but its role is not established in immunocompetent individuals. To study the possible role of EBV in PCNSL in immunocompetent individuals. Retrospective study. Thirty patients with PCNSL were studied immunohistochemically with antibodies to CD45, CD20, CD3 and EBV latent membrane protein-1 (EBV LMP-1). In situ hybridization was done in 19 patients where enough tissue was available using a specific oligonucleotide probe for EBV-Early RNA (EBER). All the patients were immunocompetent and mean age was 41.6 years. Histologically they were diffuse large cell lymphoma: 25 (83.3%) were B cell, 1(3.3%) was T cell and 4 (13.3%) were unclassified. EBV LMP-1 showed variable membrane and cytoplasmic positivity in 24 (80%) patients. In situ hybridization for EBER was negative in all the 19 patients studied. In this region of the world probably EBV has no etiologic role in PCNSL in immunocompetent individuals.

  18. Epstein-Barr virus-related cutaneous necrotizing vasculitis in a girl heterozygous for factor V Leiden.

    Science.gov (United States)

    Guerriero, Cristina; Moretta, Gaia; Bersani, Giulia; Valentini, Piero; Gatto, Antonio; Rigante, Donato

    2017-12-01

    Necrotizing vasculitides are basically characterized by vessel wall neutrophil infiltration and necrosis and they can occur as a primary process or secondary to an underlying disease. Although Henoch-Schönlein purpura (HSp) is the more frequent primary vasculitis in childhood, sometimes it has to be distinguished from other secondary vasculitides induced by infections, drugs, vaccines, or immune-mediated disorders. We report a case of a 14-year-old girl with cutaneous necrotizing vasculitis, appearing in the course of acute Epstein-Barr virus infection. Physical examination revealed highly aching erythematous-purple lesions with reticular edges localized on the back of feet. Pain was non-responsive to ibuprofen and required administration of tapentadol and pregabalin. The patient was also heterozygous for factor V Leiden that might have contributed to the development of cutaneous painful lesions. To our knowledge this is the first documented pediatric case of necrotizing vasculitis associated with acute EBV infection in a girl heterozygous for factor V Leiden. In this patient the severity of skin manifestations might have been influenced by the concomitant factor V Leiden, which gave rise to hypercoagulability and occlusive vasculopathy with markedly severe pain, a symptom rather infrequent in other childhood vasculitides.

  19. Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells.

    Science.gov (United States)

    Kalchschmidt, Jens S; Bashford-Rogers, Rachael; Paschos, Kostas; Gillman, Adam C T; Styles, Christine T; Kellam, Paul; Allday, Martin J

    2016-05-30

    Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence variation in immunoglobulins (Igs) during the process of somatic hypermutation (SHM) and also Ig class switching, can have a potent mutator phenotype in the development of lymphoma. Using various Epstein-Barr virus (EBV) recombinants, we provide definitive evidence that the viral nuclear protein EBNA3C is essential in EBV-infected primary B cells for the induction of AID mRNA and protein. Using lymphoblastoid cell lines (LCLs) established with EBV recombinants conditional for EBNA3C function, this was confirmed, and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to highly conserved regulatory elements located proximal to and upstream of the AICDA transcription start site. EBNA3C binding initiated epigenetic changes to chromatin at specific sites across the AICDA locus. Deep sequencing of cDNA corresponding to the IgH V-D-J region from the conditional LCL was used to formally show that SHM is activated by functional EBNA3C and induction of AID. These data, showing the direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiology of B cell cancers, including endemic Burkitt lymphoma. © 2016 Kalchschmidt et al.

  20. Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Diseases: Three Distinct Cases from a Single Center

    Directory of Open Access Journals (Sweden)

    Şule Mine Bakanay

    2014-03-01

    Full Text Available Three cases of Epstein-Barr virus (EBV-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

  1. Detection of Epstein-Barr virus infection subtype in patients with multiple sclerosis by indirect immunofluorescence assay

    Directory of Open Access Journals (Sweden)

    Shan-Chao Zhang

    2014-06-01

    Full Text Available Aim: The aim was to investigate the infectious conditions of Epstein-Barr virus (EBV in patients with multiple sclerosis (MS. Methods: Cerebrospinal fluid (CSF of 20 patients with MS and 20 with other neurological diseases (OND were tested with indirect immunofluorescence for anti-EBV capsid antigen (EBV-CA immunoglobulin G (IgG, IgG affinity for anti-EBV-CA, anti-EBV-CA immunoglobulin M (IgM, anti-EBV early antigen (EBV-EA IgG and anti-EBV nuclear antigen (EBNA IgG. According to the pattern of antibodies in CSF, infection rates of acute, chronic, primary, recurrent, and past infections were analyzed in the two groups of patients. Results: There were no significant differences in anti-EBV-CA, anti-EBC-EA, and anti-EBNA antigen IgG in CSF between MS and OND patients (P > 0.05. The positive rate of low affinity for anti-EBV-CA IgG in MS patients was significantly higher than that for OND patients (75% vs. 40%, P < 0.05. Furthermore, significant differences in the positive rate of anti-EBV-CA IgM were found between MS and OND patients (70% vs. 25%, P < 0.05. Of the MS patients, 75% were in an EBV acute infection state compared with 40% of OND patients (P < 0.05. Conclusion: Acute infection of EBV closely correlates with the occurrence of MS.

  2. Impact of Plasma Epstein-Barr Virus-DNA and Tumor Volume on Prognosis of Locally Advanced Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Meng Chen

    2015-01-01

    Full Text Available This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV- DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC. A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx, the lymph node lesions (GTVnd, and the total GTV before treatment were 72.46, 23.26, and 106.25 cm3, respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P<0.01. The 2-year overall survival (OS rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P=1.000, and the disease-free survival (DFS rates were 94.4% and 80.8% (P=0.044, respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

  3. HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Lundgren, Jens Dilling

    1991-01-01

    All 51 cases of HIV-related malignant lymphoma in Denmark diagnosed from 1983 to 1989 were reviewed. There were 12 Burkitt-type lymphomas, 30 immunoblast-rich lymphomas and 9 other lymphomas. Patients with immunoblast-rich lymphomas had significantly lower CD4 cell counts (median 60 vs. 188 x 10......(6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0.......10). Compared with EBV DNA-negative tumours EBV DNA-positive tumours were associated with lower CD4 cell counts (median 39 vs. 188 x 10(6)/l, P = 0.01). It is concluded that two main types of HIV-related malignant lymphoma exist. One is associated with severe immunosuppression, is often of immunoblast...

  4. Epstein-Barr virus-associated adult respiratory distress syndrome in a patient with AIDS: a case report and review.

    Science.gov (United States)

    Stopyra, G A; Multhaupt, H A; Alexa, L; Husson, M; Stern, J; Warhol, M J

    1999-10-01

    Epstein-Barr virus (EBV) infection has been associated with fatal pneumonitis in immunocompetent patients. We present a case of fatal adult respiratory distress syndrome caused by EBV infection in a patient with acquired immunodeficiency syndrome (AIDS), to our knowledge the first such reported case, along with a survey of archival autopsy cases to assess baseline expression of EBV in AIDS patients. The case patient's autopsy material was studied exhaustively for infectious agents by culture, histochemistry, and immunohistochemistry, with negative results. Formalin-fixed paraffin-embedded lung, spleen, lymph node, and liver tissue were further studied by in situ hybridization using a probe for EBV early RNA (EBER, Kreatech). The same method was applied to lymphoid tissues from eight other archival AIDS autopsy cases. Case patient tissues were also examined by electron microscopy. Strikingly numerous lymphocytes were positive for EBV early RNA in the case patient's spleen, lymph nodes, and hepatic portal areas. In addition to positive lymphocytes in the lung, EBV-infected pneumocytes were also present. Electron microscopy also demonstrated viral material in lymphocytes and pneumocytes. Of the archival cases studied, only one spleen was found to have rare positive lymphocytes. Primary or reactivation EBV infection may represent a previously underreported cause of morbidity and mortality in AIDS patients. Autopsy tissues from AIDS patients do not routinely show overexpression of EBV early RNA by in situ hybridization, making this technique ideal for assessing the contribution of EBV to terminal events in these patients.

  5. TaqMan Real-Time Quantification of Epstein-Barr Virus in Severe Early Childhood Caries.

    Science.gov (United States)

    Yildirim, Sibel; Yildiz, Esma; Kubar, Ayhan

    2010-01-01

    Early childhood caries (ECC) has several risk factors and it is important stressful/painful events of childhood and immunosuppression may occur during this unique rampant caries pattern. The changes in the host immune competence by compromised cellular immune system functions can activate Epstein Barr virus (EBV). The objective of this study was to determine whether the supragingival plaque samples of severe-ECC (S-ECC) patients harbor more EBV load than the non-carious healthy children by quantitative TaqMan Real-Time polymerase chain reaction (PCR). Sixty subjects, including 30 S-ECC patients as well as age and gender matched 30 caries-free patients were studied. The supragingival plaque samples were collected from patients by brushing their teeth for 1 minute and the toothbrush was washed in 1 ml of sterile deionized water. After viral DNA extraction, TaqMan real-time PCR assay was used to quantify EBV DNA. Dental treatments were completed for all S-ECC patients and they were called for routine controls. Only 10 treated S-ECC patients were come to the 3(rd) months' control and post-treatment viral sampling was made in the same manner. EBV DNA was detected 16 of 30 S-ECC patients and 6 of the healthy controls (Pstudy suggest that oro-dental hygiene motives of S-ECC patients might be important contributory factor for S-ECC and EBV would not be involved in the etiopathogenesis of ECC.

  6. Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor prognosis of head and neck carcinomas.

    Science.gov (United States)

    Turunen, Aaro; Rautava, Jaana; Grénman, Reidar; Syrjänen, Kari; Syrjänen, Stina

    2017-04-18

    Epstein-Barr virus (EBV) is the main cause of nasopharyngeal carcinoma (NPC), also found in other head and neck carcinomas (HNSCCs) where its role remains controversial. EBV was found in 80% and 21% of the samples with PCR and ISH (in cancer cells), respectively. Eight of ISH-positive samples were not NPCs. EBER-RNA detection in carcinoma cells was associated with worse prognosis, whether or not NPCs were included. HPV/EBV and HSV/HPV coinfections associated with a shorter survival. LMP-1 expression, positive in 51% of samples did not correlate with the disease outcome. We analyzed EBV in 73 HNSCC samples with a known HPV and HSV-1 status, using in situ hybridization (ISH) and immunohistochemistry (IHC) for EBV-early transcripts (EBER) and LMP-1 protein, respectively. EBV-DNA was detected with a Luminex-based method. The results were correlated with HPV-status and disease outcome. EBV is transcriptionally active in NPC cells but also in a subgroup of other HNSCCs.

  7. Conserved sequences of BART and BHRF regions encoding viral microRNAs in Epstein-Barr virus-associated lymphoma.

    Science.gov (United States)

    Sunagawa, Keishin; Hishima, Tsunekazu; Fukumoto, Hitomi; Hasegawa, Hideki; Katano, Harutaka

    2017-07-14

    Epstein-Barr virus (EBV) encodes at least 25 pri-microRNAs (miRNAs) in two regions of its DNA genome, BART and BHRF. B95-8, an EBV reference strain, has a deletion in the BART region. However, no information is available on the deletions or mutations in the BART and BHRF regions in clinical samples of EBV-associated lymphoma. Nine DNA fragments encoding miR-BARTs and two coding miR-BHRF1s were amplified by PCR from DNA samples extracted from 16 cases of EBV-associated lymphoma. All the PCR products were sequenced directly. DNA fragments encoding miR-BARTs and miR-BHRF1-1 were successfully amplified from all samples. An adenine-to-guanine mutation in the DNA fragment encoding miR-BART2-3p was detected in four of the 16 cases, and a cytosine-to-thymidine mutation in the DNA fragment encoding miR-BART11-3p was detected in one of the 16 samples. These mutations were not associated with any histological categories of lymphoma. In conclusion, mutations were rarely observed in the DNA encoding viral miRNAs in cases of lymphoma. This suggests that the DNA sequences of EBV-encoded miR-BARTs and miR-BHRF1-1 are conserved in EBV-associated lymphoma.

  8. Performance of the Real-Q EBV Quantification Kit for Epstein-Barr Virus DNA Quantification in Whole Blood.

    Science.gov (United States)

    Huh, Hee Jae; Park, Jong Eun; Kim, Ji Youn; Yun, Sun Ae; Lee, Myoung Keun; Lee, Nam Yong; Kim, Jong Won; Ki, Chang Seok

    2017-03-01

    There has been increasing interest in standardized and quantitative Epstein-Barr virus (EBV) DNA testing for the management of EBV disease. We evaluated the performance of the Real-Q EBV Quantification Kit (BioSewoom, Korea) in whole blood (WB). Nucleic acid extraction and real-time PCR were performed by using the MagNA Pure 96 (Roche Diagnostics, Germany) and 7500 Fast real-time PCR system (Applied Biosystems, USA), respectively. Assay sensitivity, linearity, and conversion factor were determined by using the World Health Organization international standard diluted in EBV-negative WB. We used 81 WB clinical specimens to compare performance of the Real-Q EBV Quantification Kit and artus EBV RG PCR Kit (Qiagen, Germany). The limit of detection (LOD) and limit of quantification (LOQ) for the Real-Q kit were 453 and 750 IU/mL, respectively. The conversion factor from EBV genomic copies to IU was 0.62. The linear range of the assay was from 750 to 10⁶ IU/mL. Viral load values measured with the Real-Q assay were on average 0.54 log₁₀ copies/mL higher than those measured with the artus assay. The Real-Q assay offered good analytical performance for EBV DNA quantification in WB.

  9. Comparison of Epstein-Barr virus genotypes and clinicohistopathological features of nasopharyngeal carcinoma between Guilin, China and Fukuoka, Japan.

    Science.gov (United States)

    Zhou, Yingqiong; Nabeshima, Kazuki; Koga, Kaori; Aoki, Mikiko; Hayashi, Hiroyuki; Hamasaki, Makoto; Iwasaki, Hiroshi

    2008-06-01

    Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to Guilin, China, but not Fukuoka, Japan. To examine whether the NPC in these two cities are distinct in their association with EBV, we analyzed the histology and EBV genotypes in 163 NPC from Guilin, 52 NPC from Fukuoka and non-cancerous control nasopharyngeal tissues (n=22 each) by in situ hybridization and PCR. The proportion of EBV-positive NPC from Guilin (95%) was higher than that of Fukuoka (55%, pGuilin (95 vs. 46%) and Fukuoka (55 vs. 32%). Histopathologically, non-keratinizing carcinoma and the undifferentiated subtype (NKC-U) were predominant in Guilin (84%), while the proportion of keratinizing squamous cell carcinoma (KSCC, 38%) was similar to NKC-U (42%) in Fukuoka. EBV-positivity was higher in NKC-U than KSCC in the two cities. EBV genotype A was highly prevalent in Guilin and Fukuoka. However, the BamHI f variant was predominant in Guilin (79%), whereas all the identified types were the F prototype in Fukuoka. The genetic structure and biological functions of the EBV strain associated with endemic NPC in Guilin were probably different from those of Fukuoka. The genetic differences between Guilin and Fukuoka may mirror the differences in histology and patient profiles.

  10. [Recurrence of chronic active Epstein-Barr virus infection presenting with myelopathy after umbilical cord blood transplantation].

    Science.gov (United States)

    Watanabe, Shohei; Okada, Masaya; Tokugawa, Tazuko; Sawada, Akihiro; Ogawa, Hiroyasu; Yoshikawa, Hiroo

    2014-01-01

    A 38-year-old man was admitted to our hospital with neck pain, dysesthesia of both hands, and weakness of the left upper limb. He had been diagnosed with a chronic active Epstein-Barr virus infection (CAEBV) at the age of 34 and had undergone umbilical cord blood transplantation at the age of 37. MRI of the spinal cord revealed an intramedullary hyperintense lesion on T₂-weighted images with gadolinium enhancement. Because his laboratory tests revealed proliferation of CD19(+) lymphocytes in the peripheral blood, and EBV DNA was detected in both peripheral blood and CSF, he was diagnosed as having post-transplant EBV associated lymphoproliferative disease. However, chemotherapy did not alleviate his symptoms. At a later time, quantitative chimerism analysis of his CSF showed a higher proportion of lymphocytes that had originated from the recipient. Finally, he was diagnosed as having a recurrence of CAEBV in the central nervous system, and his symptoms were restored by intrathecal chemotherapy (methotrexate, cytosine arabinoside, and prednisolone). Quantitative chimerism analysis of CSF was useful for diagnosing the recurrence of CAEBV in the central nervous system.

  11. Identification and Characterization of Epstein-Barr Virus Genomes in Lung Carcinoma Biopsy Samples by Next-Generation Sequencing Technology.

    Science.gov (United States)

    Wang, Shanshan; Xiong, Hongchao; Yan, Shi; Wu, Nan; Lu, Zheming

    2016-05-18

    Epstein-Barr virus (EBV) has been detected in the tumor cells of several cancers, including some cases of lung carcinoma (LC). However, the genomic characteristics and diversity of EBV strains associated with LC are poorly understood. In this study, we sequenced the EBV genomes isolated from four primary LC tumor biopsy samples, designated LC1 to LC4. Comparative analysis demonstrated that LC strains were more closely related to GD1 strain. Compared to GD1 reference genome, a total of 520 variations in all, including 498 substitutions, 12 insertions, and 10 deletions were found. Latent genes were found to harbor the most numbers of nonsynonymous mutations. Phylogenetic analysis showed that all LC strains were closely related to Asian EBV strains, whereas different from African/American strains. LC2 genome was distinct from the other three LC genomes, suggesting at least two parental lineages of EBV among the LC genomes may exist. All LC strains could be classified as China 1 and V-val subtype according to the amino acid sequence of LMP1 and EBNA1, respectively. In conclusion, our results showed the genomic diversity among EBV genomes isolated from LC, which might facilitate to uncover the previously unknown variations of pathogenic significance.

  12. Conserved cell cycle regulatory properties within the amino terminal domain of the Epstein-Barr virus nuclear antigen 3C

    International Nuclear Information System (INIS)

    Sharma, Nikhil; Knight, Jason S.; Robertson, Erle S.

    2006-01-01

    The gammaherpesviruses Rhesus lymphocryptovirus (LCV) and Epstein-Barr virus (EBV) are closely related phylogenetically. Rhesus LCV efficiently immortalizes Rhesus B cells in vitro. However, despite a high degree of conservation between the Rhesus LCV and EBV genomes, Rhesus LCV fails to immortalize human B cells in vitro. This species restriction may, at least in part, be linked to the EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), known to be essential for B cell transformation. We compared specific properties of EBNA3C, a well-characterized and essential EBV protein, with its Rhesus counterpart to determine whether EBNA3C phenotypes which contribute to cell cycle regulation are conserved in the Rhesus LCV. We show that both EBNA3C and Rhesus EBNA3C bind to a conserved region of mammalian cyclins, regulate pRb stability, and modulate SCF Skp2 -dependent ubiquitination. These results suggest that Rhesus LCV restriction from human B cell immortalization is independent of the conserved cell cycle regulatory functions of the EBNA3C protein

  13. The incidence of epstein-barr virus primary infection among suspected patients referred to namazi hospital of shiraz, iran.

    Science.gov (United States)

    Moeini, Mahsa; Ziyaeyan, Mazyar; Asaei, Sadaf; Behzadi, Mohammad Amin

    2015-04-01

    Many children become infected with Epstein-Barr virus (EBV) during their childhood. Since the clinical profile of EBV primary infection is challenging, it is important to use the best diagnostic clinical means. Detection of IgM against viral capsid antigen (VCA) by ELISA has been shown to be a reliable method. This study was conducted to demonstrate the incidence of EBV primary infection, among suspected patients referred to Namazi hospital, Shiraz, Iran. The sample included 346 patients with an age range of 0 to 20 years (6.31 ± 4.66: 10.97 years). A volume of 5 mL of blood was collected from each case. The patients were divided to four age groups. The sera were tested for the presence of VCA-IgM by commercially available Anti-EBV-VCA ELISA kit. The results indicated that 104 (30.0%) of the patients were EBV VCA IgM positive, with no significant difference in the incidence of EBV primary infection between males and females. However, the incidence of infection was significantly different between age group I (0 - 5 years) and III (11 - 15 years), and also between age group I (0 - 5 years) and IV (16 - 20 years) (P < 0.05). Considering the results, accurate and on time diagnosis of EBV primary infection in both children and adolescents will help prevent unnecessary hospitalization, medication and incorrect medical decisions. In addition, this will decrease further treatment costs and related medical procedures.

  14. Ekspresi produk gen laten virus epstein-barr pada karsinoma sel skuamosa rongga mulut (The expressions of latent gene product of epstein-barr virus in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Theresia Indah Budhy S

    2005-06-01

    Full Text Available Squamous cell carcinoma (SCC is a type of cancer often found in oral cavity and the area of head and neck at about 90%. Based on the geographical incidence oral SCC (OSCC has many types of different emerging. This case probably has connection with ethnic group, habit and social and economical condition. In East Java, the incidence is about 2.64% and it increases every year. The virus is known as one of the main factors that result in this disease. Epstein-Barr virus (EBV has potential capability of carcinogenesis. EBV is the family of herpesviridae that can infect cell through the linking of CD 21 receptor of the epithel with glycol protein 350/220 of the virus capsule. After primary infection, the virus will form latent-gene in human cell. Periodically, the latent-gene product can disturb proliferation and apoptotic regulator. In Indonesia, the expression of EBV latent geneproduct in the OSCC has not been reported yet. This study wanted to know the expression of EBV latent gene product found in the OSCC. This study found 25 cases of OSCC in which 17 were infected by EBV. Detection of EBV infection could be done by insitu hybridization to identify RNA EBV (EBER. To find the expression of EBV latent gene product, immunohistochemical analysis was done. The conclusion was that the emerging of expression of EBV latent gene product in OSCC were latent membrane protein-1 (LMP-1, EBV nuclear antigen-1 (EBNA-1 and RNA EBV (EBER. They were 28.28%, 25.26% and 46.47%. It was suggested to do the following research on OSCC infected by EBV and the emerging of expression of EBV latent gene product with regulator gene of proliferation and apoptotic in OSCC.

  15. Determination of Roles of Microgravity and Ionizing Radiation on the Reactivation of Epstein-Barr Virus In Vitro

    Science.gov (United States)

    Mehta, Satish K; Renner, Ashlie; Stowe, Raymond; Bloom, David; Pierson, Duane

    2015-01-01

    Astronauts experience symptomatic and asymptomatic herpes virus reactivation during spaceflight. We have shown increases in reactivation of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella zoster virus (VZV) and shedding in body fluids (saliva and urine) in astronauts during space travel. Alterations in immunity, increased stress hormone levels, microgravity, increased radiation, and other conditions unique to spaceflight may promote reactivation of latent herpes viruses. Unique mechanico-physico forces associated with spaceflight can have profound effects on cellular function, especially immune cells. In space flight analog studies such as Antarctica, bed rest studies, and NASA's undersea habitat (Aquarius), reactivation of these viruses occurred, but to a lesser extent than spaceflight. Spaceflight analogs model some spaceflight factors, but none of the analogs recreates all factors experienced in space. Most notably, microgravity and radiation are not included in many analogs. Stress, processed through the HPA axis and SAM systems, induces viral reactivation. However, the respective roles of microgravity and increased space radiation levels or if any synergy exists are not known. Therefore, we studied the effect of modeled space radiation and/or microgravity, independent of the immune system on the changes in cellular gene expression that results in viral (EBV) reactivation. The effects of modeled microgravity and low shear on EBV replication and cellular and EBV gene expression were studied in human B-lymphocyte cell cultures. Latently infected B-lymphocytes were propagated in the rotating wall bioreactor and irradiated with the various dosages of gamma irradiation. At specific time intervals following exposure to modeled microgravity, the cells and supernatant were harvested and reactivation of EBV were assessed by measuring EBV and gene expression, DNA methylation, and infectious virus production.

  16. Epstein-Barr virus-associated leiomyosarcoma with cutaneous involvement in an African child with human immunodeficiency virus: a case report and review of the literature.

    Science.gov (United States)

    Tetzlaff, Michael T; Nosek, Carl; Kovarik, Carrie L

    2011-09-01

    Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) are infrequently encountered lesions restricted to immunocompromised patients. However, they represent the second most common tumor in children with human immunodeficiency virus (HIV) infection. We report a case of a progressively enlarging abdominal mass with cutaneous involvement in an HIV-infected, 4-year-old African girl in Malawi with clinical acquired immunodeficiency syndrome on highly active antiretroviral therapy. Analysis of an excisional specimen revealed a well-differentiated leiomyosarcoma and subsequent studies revealed diffuse nuclear positivity for Epstein-Barr virus early RNAs in lesional cells. We present a report of this case and provide a summary of the literature regarding SMTs in pediatric HIV-infected patients. In addition, we draw attention to the cutaneous manifestations of SMTs in immunosuppressed populations. We highlight EBV-related SMTs as a potential cutaneous complication of HIV infection in children and immunosuppressed patients populations as a whole. 2011 John Wiley & Sons A/S.

  17. Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark diagnosed from 1990-1996: clinical features, histopathology, and association with Epstein-Barr virus and human herpesvirus-8

    DEFF Research Database (Denmark)

    Hansen, P B; Penkowa, M; Kirk, O

    2000-01-01

    The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8 (...

  18. Oral dysplasia and squamous cell carcinoma: correlation between increased expression of CD21, Epstein-Barr virus and CK19.

    Science.gov (United States)

    Jiang, Ru; Gu, Xin; Moore-Medlin, Tara N; Nathan, Cherie-Ann; Hutt-Fletcher, Lindsey M

    2012-09-01

    Epstein-Barr virus is an orally transmitted human gammaherpesvirus that infects B lymphocytes and epithelial cells. Although most primary infections are asymptomatic, long term carriage of the virus can be associated with either lymphoid or epithelial malignancies. The association of EBV with oral squamous cell carcinomas is sporadic and it is uncertain if the virus is involved in initiation of the tumor or, possibly, in its progression. Complement receptor type 2, CR2 or CD21, is a receptor for the major attachment protein of EBV, which significantly enhances epithelial cell infection, but its expression on normal tissues is restricted to tonsil and adenoid epithelium. As cells become dysplastic they are reported to express higher levels of CK19. We sought to evaluate whether CD21 and CK19 expression change as oral epithelial cells outside Waldeyer's ring become dysplastic. Epithelial cells were isolated by laser capture microdissection and levels of CD21, CK19 and EBV RNA were measured by quantitative reverse transcriptase PCR. We report that expression of CD21 increases in frequency and intensity as oral epithelial cells become more dysplastic and that expression correlates with an increase in infection by EBV. Tumors or dysplastic lesions that carry EBV also generally express higher levels of CK19 than those that do not. The findings suggest that dysplasia may make cells more susceptible to infection by EBV and that infection by the virus may alter the phenotype of the infected cell in a manner which could affect prognosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. No evidence for the presence of Epstein-Barr virus in squamous cell carcinoma of the mobile tongue.

    Science.gov (United States)

    Wilms, Torben; Khan, Gulfaraz; Coates, Philip J; Sgaramella, Nicola; Fåhraeus, Robin; Hassani, Asma; Philip, Pretty S; Norberg Spaak, Lena; Califano, Luigi; Colella, Giuseppe; Olofsson, Katarina; Loizou, Christos; Franco, Renato; Nylander, Karin

    2017-01-01

    Squamous cell carcinoma of the head and neck (SCCHN) comprises a large group of cancers in the oral cavity and nasopharyngeal area that typically arise in older males in association with alcohol/tobacco usage. Within the oral cavity, the mobile tongue is the most common site for tumour development. The incidence of tongue squamous cell carcinoma (TSCC) is increasing in younger people, which has been suggested to associate with a viral aetiology. Two common human oncogenic viruses, human papilloma virus (HPV) and Epstein-Barr virus (EBV) are known causes of certain types of SCCHN, namely the oropharynx and nasopharynx, respectively. EBV infects most adults worldwide through oral transmission and establishes a latent infection, with sporadic productive viral replication and release of virus in the oral cavity throughout life. In view of the prevalence of EBV in the oral cavity and recent data indicating that it infects tongue epithelial cells and establishes latency, we examined 98 cases of primary squamous cell carcinoma of the mobile tongue and 15 cases of tonsillar squamous cell carcinoma for the presence of EBV-encoded RNAs (EBERs), EBV DNA and an EBV-encoded protein, EBNA-1. A commercially available in situ hybridisation kit targeting EBER transcripts (EBER-ISH) showed a positive signal in the cytoplasm and/or nuclei of tumour cells in 43% of TSCCs. However, application of control probes and RNase A digestion using in-house developed EBER-ISH showed identical EBER staining patterns, indicating non-specific signals. PCR analysis of the BamH1 W repeat sequences did not identify EBV genomes in tumour samples. Immunohistochemistry for EBNA-1 was also negative. These data exclude EBV as a potential player in TSCC in both old and young patients and highlight the importance of appropriate controls for EBER-ISH in investigating EBV in human diseases.

  20. Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants.

    Directory of Open Access Journals (Sweden)

    Beth Holder

    2010-11-01

    Full Text Available Epstein-Barr virus (EBV and cytomegalovirus (CMV are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.

  1. No evidence of transfusion transmission of Adenovirus and Epstein-Barr virus infections in paediatric recipients post-bone marrow transplant.

    Science.gov (United States)

    Patel, P; Tuke, P; Tettmar, K; Cloutman-Green, E; Hartley, J; Klein, N; Veys, P; Tedder, R S

    2015-07-01

    Adenovirus and Epstein-Barr virus can cause significant morbidity and mortality in paediatric patients post-bone marrow transplant. The source of infection is thought to be either reactivation of latent viruses or primary infection. We have investigated whether transfusion of blood components from viraemic donors could provide a route of primary infection in these patients and sought the prevalence of viraemia in the blood donor population from England. In 32 linked donor/recipient samples and 300 unselected blood donors, we found no evidence to suggest that these infections in paediatric bone marrow transplant recipients had been acquired from transfused blood components. © 2015 International Society of Blood Transfusion.

  2. Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

    Science.gov (United States)

    Sinha, Mahua; Rao, Clementina Rama; Premalata, C S; Shafiulla, Mohammed; Lakshmaiah, K C; Jacob, Linu Abraham; Babu, Govind K; Viveka, B K; Appaji, L; Subramanyam, Jayshree R

    2016-01-01

    There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

  3. Epstein-Barr virus (EBV Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.

    Directory of Open Access Journals (Sweden)

    Yen-Ju Chen

    Full Text Available Epstein-Barr virus (EBV Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV, to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1 an ideal environment for virus reactivation if EBV or KSHV coexists and (2 a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.

  4. [Encephalitis due to the Epstein-Barr virus: a description of a clinical case and review of the literature].

    Science.gov (United States)

    Barón, Johanna; Herrero-Velázquez, Sonia; Ruiz-Piñero, Marina; Pedraza, M Isabel; Rojo-Rello, Silvia; Guerrero-Peral, Ángel Luis

    2013-11-16

    INTRODUCTION. Infection by the Epstein-Barr virus (EBV) -either as a primary infection, a reactivation or an active chronic infection- can give rise to several clinical forms of involvement of the central nervous system. We report a case of encephalitis due to EBV produced by viral reactivation in an immunocompetent patient which initially mimicked, from the clinical and electroencephalographic point of view, encephalitis due to type 1 herpes simplex virus (HSV-1). CASE REPORT. A 51-year-old male who had reported the presence of dorsal herpes zoster some days earlier. The patient visited the emergency department after suffering a holocranial oppressive headache and febricula for seven days; 24 hours before admission to hospital, he was suffering from drowsiness and language disorder. The neurological examination revealed stiffness in the back of the neck and dysphasia. An analysis of the cerebrospinal fluid revealed pleocytosis (422 cells/mm(3)) with 98% of mononuclear cells and normal protein and glucose concentration levels in cerebrospinal fluid. Magnetic resonance imaging of the brain and electroencephalogram readings were normal with periodic lateralised epileptiform discharges in the left temporal region. Intravenous acyclovir treatment was initiated, but renal failure meant it had to be changed to oral valaciclovir with clinical resolution and improvement of the liquoral parameters. Polymerase chain reaction in the cerebrospinal fluid was positive for EBV and negative for the other neurotropic viruses. In blood, the serology test for EBV with IgG was positive, while IgM and heterophile antibody tests were negative. CONCLUSIONS. EBV infection can give rise to acute disseminated encephalomyelitis or affect several locations in the central nervous system, especially the cerebellum. Clinical pictures mimicking HSV-1 are less frequent. When encephalitis is related to viral reactivation, precipitating factors can be detected, as in our case.

  5. The biological properties of different Epstein-Barr virus strains explain their association with various types of cancers.

    Science.gov (United States)

    Tsai, Ming-Han; Lin, Xiaochen; Shumilov, Anatoliy; Bernhardt, Katharina; Feederle, Regina; Poirey, Remy; Kopp-Schneider, Annette; Pereira, Bruno; Almeida, Raquel; Delecluse, Henri-Jacques

    2017-02-07

    The Epstein-Barr virus (EBV) is etiologically associated with the development of multiple types of tumors, but it is unclear whether this diversity is due to infection with different EBV strains. We report a comparative characterization of SNU719, GP202, and YCCEL1, three EBV strains that were isolated from gastric carcinomas, M81, a virus isolated in a nasopharyngeal carcinoma and several well-characterized laboratory type A strains. We found that B95-8, Akata and GP202 induced cell growth more efficiently than YCCEL1, SNU719 and M81 and this correlated positively with the expression levels of the viral BHRF1 miRNAs. In infected B cells, all strains except Akata and B95-8 induced lytic replication, a risk factor for carcinoma development, although less efficiently than M81. The panel of viruses induced tumors in immunocompromised mice with variable speed and efficacy that did not strictly mirror their in vitro characteristics, suggesting that additional parameters play an important role. We found that YCCEL1 and M81 infected primary epithelial cells, gastric carcinoma cells and gastric spheroids more efficiently than Akata or B95-8. Reciprocally, Akata and B95-8 had a stronger tropism for B cells than YCCEL1 or M81. These data suggest that different EBV strains will induce the development of lymphoid tumors with variable efficacy in immunocompromised patients and that there is a parallel between the cell tropism of the viral strains and the lineage of the tumors they induce. Thus, EBV strains can be endowed with properties that will influence their transforming abilities and the type of tumor they induce.

  6. Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway.

    Science.gov (United States)

    Lu, Yuanjun; Qin, Zailong; Wang, Jia; Zheng, Xiang; Lu, Jianhong; Zhang, Xuemei; Wei, Lingyu; Peng, Qiu; Zheng, Ying; Ou, Chunlin; Ye, Qiurong; Xiong, Wei; Li, Guiyuan; Fu, Yuxin; Yan, Qun; Ma, Jian

    2017-01-01

    Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3'UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance. © 2017 S. Karger AG, Basel.

  7. Desarrollo de improntas para el diagnóstico del virus Epstein-Barr por inmunofluorescencia indirecta Development of slides for Epstein-Barr virus diagnosis by indirect immunofluorescence

    Directory of Open Access Journals (Sweden)

    Germán R. Pérez

    2005-08-01

    Full Text Available El virus de Epstein-Barr (VEB es el principal agente oncogénico linfotrópico dentro de la familia Herpesviridae y se encuentra mundialmente distribuido. La primoinfección se produce en adultos jóvenes y se manifiesta como mononucleosis infecciosa. La detección de anticuerpos anti-viral capside antigen (VCA indica infección previa o presente con VEB. Además, se observan títulos elevados de anticuerpos anti-VCA en las enfermedades neoplásicas asociadas al VEB como los linfomas, en individuos HIV-positivos. El objetivo de este estudio fue el desarrollo y puesta a punto de improntas de células P3HR1 para la detección serológica del VEB por técnicas de inmunofluorescencia indirecta (IFI. Se estimularon cultivos de células P3HR1 en crecimiento exponencial con phorbol-12-mirystoil-13-acetato, y se recolectaron alícuotas a distintos tiempos para realizar improntas. Se realizó una IFI con cada impronta usando como anticuerpo primario un suero VEB-positivo. Se observó un aumento del 11% en la expresión del VCA a las 40 horas post-estimulación, decayendo al 3.5% a las 48 horas. Estos datos fueron corroborados por ensayo de western blot con inmunodetección. La precisión intra- e inter-lote de las improntas fue evaluada para anticuerpos IgM e IgG, con sueros probados previamente por equipos para esta determinación disponibles en el mercado para el VEB y con sueros reactivos para otros miembros de la familia Herpesviridae. No se obtuvieron resultados falsos-negativos ni falsos-positivos para el VEB ni se observó reactividad cruzada con otros herpesvirus. Las improntas desarrolladas constituyen un instrumento para el diagnóstico de la primoinfección del VEB y la detección serológica de anticuerpos IgG anti-VCA de neoplasias asociadas al VEB.Epstein-Barr virus (EBV is the main oncogenic lymphotropic agent of the Herpesviridae family and is globally distributed. EBV acute infection occurs in young adults producing infectious

  8. Characterization of Epstein-Barr virus-encoded small RNA gene variations in virus associated lymphomas in Northern China.

    Science.gov (United States)

    Zhao, Zhenzhen; Sun, Lingling; Liu, Song; Shu, Jun; Luo, Bing

    2017-06-01

    Epstein-Barr virus (EBV)-encoded small RNAs (EBER1 and EBER2) are highly expressed in all forms of EBV latency in EBV-associated malignancies. EBER gene variations and their association with EBV-associated disease still remain poorly characterized. To investigate the patterns of EBER gene variations and their roles in tumorigenesis, EBER gene sequences were analyzed by nested-PCR and DNA sequencing in 101 lymphomas from Northern China, a non-nasopharyngeal carcinoma (NPC) endemic area. In addition, EBV type 1 and type 2 classifications were made by using nested-PCR assays across type-specific regions in the EBNA2 gene. EB-6m was the dominant subtype (95.0%, 96/101) in lymphoma. The distribution of the EBER subtypes in the four lymphoma groups was not significantly different (p > 0.05), neither was that of the EBNA2 type (p > 0.05). Compared with previous data in the same area, the distribution of EBER subtypes in lymphoma was similar to that in EBV-associated gastric carcinoma (EBVaGC) and throat washing (TW) from healthy donors (p > 0.05), but was significantly different from that of NPC. The EBNA2 type distribution between lymphoma and the other three groups was significantly different (p < 0.05). The proportion of type 1 and type 2 dual infections was higher in lymphoma than that in GC, NPC and TW. The mutation 7123nt A → T was identified in 11 of 101 (10.9%, 11/101) lymphomas, significantly more than that in EBV-associated gastric carcinomas (EBVaGC) (0%, 0/50) and throat washings (TWs) from healthy donors (3.3%, 3/92) (p < 0.05). These findings indicate that EBER subtypes may not be associated with pathogenesis of lymphoma, but that a point mutation at position 7123nt (A → T) provides a new area for further exploration. Furthermore it is necessary to investigate the role of EBNA2-subtype mixed infections in the establishment of lymphoma.

  9. Reliability of the Siemens Enzygnost and Novagnost Epstein-Barr virus assays for routine laboratory diagnosis: agreement with clinical diagnosis and comparison with the Merifluor Epstein-Barr virus immunofluorescence assay.

    Science.gov (United States)

    Kreuzer, Christina; Nabeck, Klaus Udo; Levy, H Roma; Daghofer, Elisabeth

    2013-06-03

    Diagnosis of Epstein-Barr virus (EBV) infection is routinely conducted by clinical laboratories, especially to diagnose infectious mononucleosis. At an estimated general population incidence of 1:200, this represents a potentially significant testing burden. We evaluated the reliability of the Siemens Novagnost® and Enzygnost® EBV microtiter assays measuring VCA IgM and IgG, and EBNA-1 IgG for clinical diagnosis of EBV-related infectious mononucleosis. Remnant sera from 537 patients tested for EBV infection were used to compare the Siemens assays to each other and to the Merifluor assay. The Siemens assays are qualitative/semiquantitative, automatable enzyme immunoassays. The Merifluor assays are manual, qualitative indirect immunofluorescent assays. Testing was conducted on the Siemens and Merifluor assays in parallel. All assays were conducted and interpreted according to each manufacturer's specifications. Agreement of serostatus between each of the three assays was assessed. Discrepant results were resolved using a third method (Mikrogen recomLine). Final EBV serostatus indicated 2.9% of the population had an acute infection, 89.6% had a past infection, and 7.5% were EBV naive. All three assays demonstrated 100% agreement with acute infection. Agreement with past-infection serostatus was 99.1% for Enzygnost, between 86% and 98.8% for Novagnost, and 98.1% for Merifluor. Seronegative agreement was 100% for Enzygnost, 89.7% for Novagnost, and 92.3% for Merifluor. The Siemens Enzygnost and Novagnost EBV microtiter assays are suitable for clinical rule-in of acute EBV infection and for identifying EBV-naive individuals. Both assays also adequately identify remote EBV infections. Because these assays can be automated, they can improve speed and efficiency of EBV testing, especially in high-volume laboratories.

  10. Higher prevalence of Epstein-Barr virus DNA in deeper periodontal pockets of chronic periodontitis in Japanese patients.

    Directory of Open Access Journals (Sweden)

    Ayako Kato

    Full Text Available Periodontitis, a complex chronic inflammatory disease caused by subgingival infection, is among the most prevalent microbial diseases in humans. Although traditional microbiological research on periodontitis has focused on putative bacteria such as Porphyromonas gingivalis, the herpes virus is proposed to be involved in the pathogenesis of periodontitis because bacterial etiology alone does not adequately explain various clinical aspects. In this study, we established for the first time, more Epstein-Barr virus (EBV DNA is found deeper in periodontal pockets of chronic periodontitis in Japanese patients. Subgingival samples were collected from 85 patients with chronic periodontitis having two periodontal sites with probing depths (PD of ≤ 3 mm (shallow or ≥ 5 mm (deep and were subjected to a nested polymerase chain reaction. EBV DNA was more frequently detected in patients with deeper PD sites (66% than in those with shallow PD sites (48% or healthy controls (45%. Coexistence of EBV DNA and P. gingivalis was significantly higher in patients with deeper PD sites (40% than in those with shallow PD sites (14% or healthy controls (13%. Although no difference in clinical index for periodontitis, the odds ratio of EBV DNA in patients with deeper PD sites was 2.36, which was 2.07-fold higher than that in those with shallow PD sites. Interestingly, the odds of acquiring chronic periodontitis (PD ≥ 5 mm were higher in the presence of both EBV DNA and P. gingivalis compared with either EBV DNA or P. gingivalis only. In addition, we also observed that EBV-encoded small RNA (EBER in positive cells of human gingival tissues. These results would suggest that EBV DNA may serve as a pathogenic factor leading to chronic periodontitis among Japanese patients.

  11. Epstein-Barr virus-containing T-cell lymphoma presents with hemophagocytic syndrome mimicking malignant histiocytosis.

    Science.gov (United States)

    Su, I J; Hsu, Y H; Lin, M T; Cheng, A L; Wang, C H; Weiss, L M

    1993-09-15

    The previously designated malignant histiocytosis (MH) may include lymphoid neoplasms of T-cell lineage as well as patients with benign virus-associated hemophagocytic syndrome (VAHS). In this study, the association of Epstein-Barr virus (EBV) with T cell lymphomas which present with clinicopathologic features indistinguishable from malignant histiocytosis (MH) was investigated further. Four adult patients, three women and one man, were admitted because of fever, cutaneous lesions, hepatosplenomegaly, and jaundice. Laboratory examinations revealed pancytopenia, abnormal liver functions and coagulopathy. All patients ran a fulminant course terminating in a hemophagocytic syndrome within 1 month. Immunophenotypic study, Southern blot analysis, and in situ hybridization were performed on the specimens obtained from the four patients. The biopsy-necropsy specimens from skin, liver, spleen, and bone marrow showed infiltration of atypical large cells with reactive histiocytosis and florid hemophagocytosis activity. Based on the clinical and histologic findings, these cases would have been designated as MH by previous criteria. Immunophenotypic, Southern blot, and in situ hybridization studies, however, showed clonotypic proliferation of EBV genomes in the nuclei of the large atypical cells that expressed T-cell antigens. Therefore, these patients should be diagnosed as a recently described EBV-associated peripheral T-cell lymphoma (EBV-PTCL). EBV-PTCL may present with a fulminant hemophagocytic syndrome indistinguishable from the previously designated MH. This finding represents a step forward in our changing concept regarding MH, some of which only recently has been suggested to be of T-cell lymphoma origin. Differentiation from benign VAHS is clinically important. Features useful in this distinction are tabulated and discussed.

  12. A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Cécile Voisset

    2014-04-01

    Full Text Available Epstein-Barr virus (EBV is tightly associated with certain human cancers, but there is as yet no specific treatment against EBV-related diseases. The EBV-encoded EBNA1 protein is essential to maintain viral episomes and for viral persistence. As such, EBNA1 is expressed in all EBV-infected cells, and is highly antigenic. All infected individuals, including individuals with cancer, have CD8+ T cells directed towards EBNA1 epitopes, yet the immune system fails to detect and destroy cells harboring the virus. EBV immune evasion depends on the capacity of the Gly-Ala repeat (GAr domain of EBNA1 to inhibit the translation of its own mRNA in cis, thereby limiting the production of EBNA1-derived antigenic peptides presented by the major histocompatibility complex (MHC class I pathway. Here we establish a yeast-based assay for monitoring GAr-dependent inhibition of translation. Using this assay we identify doxorubicin (DXR as a compound that specifically interferes with the GAr effect on translation in yeast. DXR targets the topoisomerase-II–DNA complexes and thereby causes genomic damage. We show, however, that the genotoxic effect of DXR and various analogs thereof is uncoupled from the effect on GAr-mediated translation control. This is further supported by the observation that etoposide and teniposide, representing another class of topoisomerase-II–DNA targeting drugs, have no effect on GAr-mediated translation control. DXR and active analogs stimulate, in a GAr-dependent manner, EBNA1 expression in mammalian cells and overcome GAr-dependent restriction of MHC class I antigen presentation. These results validate our approach as an effective high-throughput screening assay to identify drugs that interfere with EBV immune evasion and, thus, constitute candidates for treating EBV-related diseases, in particular EBV-associated cancers.

  13. A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus.

    Science.gov (United States)

    Voisset, Cécile; Daskalogianni, Chrysoula; Contesse, Marie-Astrid; Mazars, Anne; Arbach, Hratch; Le Cann, Marie; Soubigou, Flavie; Apcher, Sébastien; Fåhraeus, Robin; Blondel, Marc

    2014-04-01

    Epstein-Barr virus (EBV) is tightly associated with certain human cancers, but there is as yet no specific treatment against EBV-related diseases. The EBV-encoded EBNA1 protein is essential to maintain viral episomes and for viral persistence. As such, EBNA1 is expressed in all EBV-infected cells, and is highly antigenic. All infected individuals, including individuals with cancer, have CD8(+) T cells directed towards EBNA1 epitopes, yet the immune system fails to detect and destroy cells harboring the virus. EBV immune evasion depends on the capacity of the Gly-Ala repeat (GAr) domain of EBNA1 to inhibit the translation of its own mRNA in cis, thereby limiting the production of EBNA1-derived antigenic peptides presented by the major histocompatibility complex (MHC) class I pathway. Here we establish a yeast-based assay for monitoring GAr-dependent inhibition of translation. Using this assay we identify doxorubicin (DXR) as a compound that specifically interferes with the GAr effect on translation in yeast. DXR targets the topoisomerase-II-DNA complexes and thereby causes genomic damage. We show, however, that the genotoxic effect of DXR and various analogs thereof is uncoupled from the effect on GAr-mediated translation control. This is further supported by the observation that etoposide and teniposide, representing another class of topoisomerase-II-DNA targeting drugs, have no effect on GAr-mediated translation control. DXR and active analogs stimulate, in a GAr-dependent manner, EBNA1 expression in mammalian cells and overcome GAr-dependent restriction of MHC class I antigen presentation. These results validate our approach as an effective high-throughput screening assay to identify drugs that interfere with EBV immune evasion and, thus, constitute candidates for treating EBV-related diseases, in particular EBV-associated cancers.

  14. Determining the correlation of Epstein-Barr virus with diffuse large B-cell lymphoma by chromogenic in situ hybridization

    Directory of Open Access Journals (Sweden)

    Kosari F

    2012-09-01

    Full Text Available Background: Diffuse large B-cell lymphoma (DLBCL is the most common type of lymphoma. There are various types of DLBCL including immunoblastic and centroblastic. Epstein-Barr virus (EBV is a member of Herpes virus family found in all human populations inducing different lymphoproliferative disorders. The role of EBV in the development of DLBCL is known. Multiple laboratory methods are available for detecting EBV. This study was conducted to determine the correlation of EBV with DLBCL in samples referred to pathology ward in Shariati and Sina Hospitals by chromogenic in situ hybridization (CISH method.Methods: In this case/control study, pathological specimens of 50 patients with DLBCL as well as 50 reactive lymph nodes and tonsils (control group were collected from archives of Shariati and Sina Hospitals and were evaluated for EBV encoded RNA (EBER expression based on CISH method. A peptide nucleic acid (PNA EBV probe (Dakocytomatin was used while all the processes were done in RNAase-free conditions using RNAase-free water, sterile gloves and samplers. Results: Out of fifty specimens in the case group, eight were positive for EBER in comparison with two in the control group (P=0.046. No statistically significant difference was observed between intranodal or extranodal samples (P=0.736 or between males and females (P=0.0746.Conclusion: Our study showed that EBV positivity for EBER in patient with DLBCL could be determined more effectively by CISH method than immunohistochemistry (IHC. Comparative analysis between CISH, PCR and IHC methods is recommended.

  15. Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.

    Directory of Open Access Journals (Sweden)

    Renfeng Li

    2015-12-01

    Full Text Available Epstein-Barr virus (EBV is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1. Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR, mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been

  16. Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34+ Cells with Epstein-Barr Virus

    Science.gov (United States)

    Islas-Ohlmayer, Miguel; Padgett-Thomas, Angela; Domiati-Saad, Rana; Melkus, Michael W.; Cravens, Petra D.; Martin, Maria del P.; Netto, George; Garcia, J. Victor

    2004-01-01

    Epstein-Barr virus (EBV)-induced lymphoproliferative disease is an important complication in the context of immune deficiency. Impaired T-cell immunity allows the outgrowth of transformed cells with the subsequent production of predominantly B-cell lymphomas. Currently there is no in vivo model that can adequately recapitulate EBV infection and its association with B-cell lymphomas. NOD/SCID mice engrafted with human CD34+ cells and reconstituted mainly with human B lymphocytes may serve as a useful xenograft model to study EBV infection and pathogenesis. We therefore infected reconstituted mice with EBV. High levels of viral DNA were detected in the peripheral blood of all infected mice. All infected mice lost weight and showed decreased activity levels. Infected mice presented large visible tumors in multiple organs, most prominently in the spleen. These tumors stained positive for human CD79a, CD20, CD30, and EBV-encoded RNAs and were light chain restricted. Their characterization is consistent with that of large cell immunoblastic lymphoma. In addition, tumor cells expressed EBNA1, LMP1, and LMP2a mRNAs, which is consistent with a type II latency program. EBV+ lymphoblastoid cell lines expressing human CD45, CD19, CD21, CD23, CD5, and CD30 were readily established from the bone marrow and spleens of infected animals. Finally, we also demonstrate that infection with an enhanced green fluorescent protein (EGFP)-tagged virus can be monitored by the detection of infected EGFP+ cells and EGFP+ tumors. These data demonstrate that NOD/SCID mice that are reconstituted with human CD34+ cells are susceptible to infection by EBV and accurately recapitulate important aspects of EBV pathogenesis. PMID:15564497

  17. [Bilateral facial nerve palsy associated with Epstein-Barr virus infection in a 3-year-old boy].

    Science.gov (United States)

    Grassin, M; Rolland, A; Leboucq, N; Roubertie, A; Rivier, F; Meyer, P

    2017-06-01

    Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We describe a case of bilateral simultaneous facial nerve palsy associated with Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to the diagnosis of EBV infection: the clinical situation (fever, stomachache, and throat infection), white blood cell count (5300/mm 3 with 70% lymphocyte count), seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a positive blood EBV polymerase chain reaction (9.3×10 3 copies of EBV-DNA). An MRI brain scan showed bilateral gadolinium enhancement of the facial nerve. A treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was implemented. Antibiotics were stopped after the diagnosis of Lyme disease was ruled out. The patient's facial weakness improved within a few weeks. Bilateral facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic in only 20% of cases. Therefore, it requires further investigation and examination to search for the underlying etiology. Lyme disease is the first infectious disease that should be considered in children, especially in endemic areas. An antibiotic treatment effective against Borrelia burgdorferi should be set up until the diagnosis is negated or confirmed. Further examination should include a blood test (such as immunologic testing, and serologic testing for viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and an MRI brain scan to exclude any serious or curable underlying etiology. Facial bilateral nerve palsy associated with EBV is rarely described in children. Neurological complications have been reported in 7% of all EBV infections. The facial nerve is the most frequently affected of all cranial nerves. Facial palsy described in EBV infections is bilateral in 35% of all cases. The physiopathology is currently unknown. Prognosis is good most of the time. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Detection of human papillomavirus and Epstein-Barr virus DNA sequences in oral mucosa of HIV-infected patients by the polymerase chain reaction.

    OpenAIRE

    Snijders, P. J.; Schulten, E. A.; Mullink, H.; ten Kate, R. W.; Jiwa, M.; van der Waal, I.; Meijer, C. J.; Walboomers, J. M.

    1990-01-01

    The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) was analyzed in 21 oral biopsy specimens of HIV-infected patients using the polymerase chain reaction (PCR) method. Biopsies were categorized as hairy leukoplakia (HL) (n = 12), candidiasis (n = 3), oral warts (n = 2), and clinically normal epithelium (n = 4). For HPV detection a modified general primer-mediated PCR method (GP-PCR), which detects a broad spectrum of HPV genotypes at sub-picogram levels, was used. Human pa...

  19. High sensitivity but normal DNA-repair activity after UV irradiation in Epstein-Barr virus-transformed lymphoblastoid cell lines from Chediak-Higashi syndrome

    International Nuclear Information System (INIS)

    Tanaka, H.; Orii, T.

    1980-01-01

    We established lymphoblastoid cell lines from 2 children with Chediak-Higashi syndrome (CHS), 2 xeroderma pigmentosum (XP) patients and control donors after transformation of peripheral lymphocytes by Epstein-Barr virus (EBV). We used these lymphoblastoid cell lines to investigate repair activity after ultraviolet irradiation. Cell survival of both CHS lymphoblastoid cell lines after irradiation by UV and treatment by 4-nitroquinoline 1-oxide (4NQO) fell between those of the XP and control cells lines. Unscheduled DNA synthesis of CHS cells after UV irradiation occured at rates similar to those of control cells. (orig.)

  20. Characterization and Intracellular Localization of the Epstein-Barr Virus Protein BFLF2: Interactions with BFRF1 and with the Nuclear Lamina

    OpenAIRE

    Gonnella, Roberta; Farina, Antonella; Santarelli, Roberta; Raffa, Salvatore; Feederle, Regina; Bei, Roberto; Granato, Marisa; Modesti, Andrea; Frati, Luigi; Delecluse, Henri-Jacques; Torrisi, Maria Rosaria; Angeloni, Antonio; Faggioni, Alberto

    2005-01-01

    We have reported in the accompanying paper that the BFRF1 protein of Epstein-Barr virus (EBV) is important for efficient primary viral envelopment and egress (A. Farina, R. Feederle, S. Raffa, R. Gonnella, R. Santarelli, L. Frati, A. Angeloni, M. R. Torrisi, A. Faggioni, and H.-J. Delecluse, J. Virol. 79:3703-3712). Here we describe the characterization of the product of the EBV BFLF2 gene, which belongs to a family of conserved herpesviral genes which include the UL31 genes of herpes simplex...

  1. Epstein-Barr Virus-Associated Lymphoepithelioma-Like Gastric Carcinoma Presenting as a Submucosal Mass: CT Findings with Pathologic Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Chang Jin; Lee, Ji Hye; Lee, Chang Kyun; Jeong, Dong Jun [Soonchunhyang University Cheonan Hospital, Cheonan(Korea, Republic of)

    2010-12-15

    A lymphoepithelioma-like carcinoma, characterized by a carcinoma with heavy lymphocyte infiltration, is one of the histological patterns observed in patients with Epstein-Barr virus (EBV)-associated gastric carcinoma. Less than half of invasive carcinomas with lymphoepithelioma-like histology can grow to make a submucosal mass. These tumors generally have a better prognosis than conventional adenocarcinomas. We report a case of an EBV-associated lymphoepitheliomalike gastric carcinoma that presented as a submucosal mass on multi-detector (MD) CT and correlate them with the pathology

  2. A rare case of acute pancreatitis and life-threatening hemolytic anemia associated with Epstein-Barr virus infection in a young healthy adult.

    Science.gov (United States)

    Singh, Sukhchain; Khosla, Pam

    2016-01-01

    Epstein-Barr virus (EBV) is a common infection that affects 95% of adults worldwide at some point during life. It is usually asymptomatic or causes a self-limiting clinical syndrome known as infectious mononucleosis. It rarely causes complications. Here, we present a case of a healthy 21-year-old female college student who suffered from severe pancreatitis and life-threatening autoimmune hemolytic anemia in association with EBV infection, and we also discuss the common presentation of EBV infection and the diagnosis and treatment of simple and complicated EBV infection. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  3. Measurement of Epstein-Barr virus DNA loads in whole blood and plasma by TaqMan PCR and in peripheral blood lymphocytes by competitive PCR.

    Science.gov (United States)

    Wadowsky, Robert M; Laus, Stella; Green, Michael; Webber, Steven A; Rowe, David

    2003-11-01

    Epstein-Barr virus (EBV) DNA load values were measured in samples of whole blood (n = 60) and plasma (n = 59) by TaqMan PCR and in samples of peripheral blood lymphocytes (PBLs) (n = 60) by competitive PCR (cPCR). The samples were obtained from 44 transplant recipients. The whole-blood and PBL loads correlated highly (r(2) > 0.900), whereas the plasma and PBL loads correlated poorly (r(2) = 0.512). Testing of whole blood by TaqMan PCR is an acceptable alternative to testing of PBLs by cPCR for quantifying EBV DNA load.

  4. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  5. Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells.

    Science.gov (United States)

    Al Tabaa, Yassine; Tuaillon, Edouard; Bollore, Karine; Foulongne, Vincent; Petitjean, Gael; Seigneurin, Jean-Marie; Duperray, Christophe; Desgranges, Claude; Vendrell, Jean-Pierre

    2009-01-15

    The Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle. Purified B lymphocytes were polyclonally stimulated and BZLF1- or gp350-secreting cells (BZLF1-SCs or gp350-SCs) were enumerated by ELISpot assays. The number of BZLF1-SCs ranged from 50 to 480/107 lymphocytes (median, 80; 25th-75th percentiles, 70-150) and gp350-SCs from 10 to 40/107 lymphocytes (median, 17; 25th-75th percentiles, 10-20). gp350-SCs represented only 7.7% to 28.6% of BZLF1-SCs (median, 15%; 25th-75th percentiles, 10.5%-20%). This EBV functional reservoir was preferentially restricted to plasma cells derived from CD27(+) IgD(-) memory B lymphocytes. In 9 of 13 subjects, EBV DNA quantification in B-cell culture supernatants gave evidence of completion of EBV lytic cycle. These results demonstrate that EBV proteins can be secreted by EBV-infected B lymphocytes from healthy carriers, a majority generating an abortive EBV lytic cycle and a minority completing the cycle.

  6. Early exposure to interleukin-21 limits rapidly generated anti-Epstein-Barr virus T-cell line differentiation.

    Science.gov (United States)

    Orio, Julie; Carli, Cédric; Janelle, Valérie; Giroux, Martin; Taillefer, Julie; Goupil, Mathieu; Richaud, Manon; Roy, Denis-Claude; Delisle, Jean-Sébastien

    2015-04-01

    The adoptive transfer of ex vivo-expanded Epstein-Barr virus (EBV)-specific T-cell lines is an attractive strategy to treat EBV-related neoplasms. Current evidence suggests that for adoptive immunotherapy in general, clinical responses are superior if the transferred cells have not reached a late or terminal effector differentiation phenotype before infusion. The cytokine interleukin (IL)-21 has shown great promise at limiting late T-cell differentiation in vitro, but this remains to be demonstrated in anti-viral T-cell lines. We adapted a clinically validated protocol to rapidly generate EBV-specific T-cell lines in 12 to 14 days and tested whether the addition of IL-21 at the initiation of the culture would affect T-cell expansion and differentiation. We generated clinical-scale EBV-restricted T-cell line expansion with balanced T-cell subset ratios. The addition of IL-21 at the beginning of the culture decreased both T-cell expansion and effector memory T-cell accumulation, with a relative increase in less-differentiated T cells. Within CD4 T-cell subsets, exogenous IL-21 was notably associated with the cell surface expression of CD27 and high KLF2 transcript levels, further arguing for a role of IL-21 in the control of late T-cell differentiation. Our results show that IL-21 has profound effects on T-cell differentiation in a rapid T-cell line generation protocol and as such should be further explored as a novel approach to program anti-viral T cells with features associated with early differentiation and optimal therapeutic efficacy. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  7. Frequency and clinical correlates of elevated plasma Epstein-Barr virus DNA at diagnosis in peripheral T-cell lymphomas

    Science.gov (United States)

    Haverkos, Bradley M.; Huang, Ying; Gru, Alejandro; Pancholi, Preeti; Freud, Aharon G.; Mishra, Anjali; Ruppert, Amy S.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Epstein Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis, but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact, and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14–37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd− patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd− tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd− patients were also EBER+. With median follow up of 24 months (range 1–96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd− patients (13 vs. 72 months; p=0.04). In this retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL. PMID:27943278

  8. Clinical significance of gastritis cystica profunda and its association with Epstein-Barr virus in gastric cancer.

    Science.gov (United States)

    Choi, Min-Gew; Jeong, Ji Yun; Kim, Kyoung-Mee; Bae, Jae Moon; Noh, Jae Hyung; Sohn, Tae Sung; Kim, Sung

    2012-11-01

    Gastritis cystica profunda (GCP) is a relatively rare disorder characterized by hyperplastic and cystic down growth of gastric glands into the submucosa. In the current study, the authors attempted to clarify the clinical and pathologic features of GCP in patients with gastric cancer. The records of 10,728 patients with gastric cancer who underwent gastric cancer surgery were reviewed. The clinicopathologic features of patients who had GCP (n = 161) were compared with the features of patients without GCP (n = 10,567). In situ hybridization to determine Epstein-Barr virus (EBV) positivity was performed in cancer tissues from patients with (n = 119) and without (n = 503) GCP. GCP was associated significantly with older age, male gender, proximal tumor location, differentiated histology and Lauren intestinal type compared with non-GCP. GCP also was present more frequently in remnant and multiple gastric cancers. Patients who had GCP presented with earlier tumor stages in terms of depth of invasion and lymph node metastasis, and they had less lymphatic and perineural invasion than patients without GCP; however, the presence of GCP was not an independent prognostic factor. The EBV-positive rate was significantly higher in the GCP group (31.1%) than in the non-GCP group (5.8%). Patients with gastric cancer who had GCP had clinicopathologic features that differed from the features observed in patients without GCP. GCP was associated significantly with EBV-positive gastric cancers, and its possible role as a premalignant lesion needs to be clarified. Copyright © 2012 American Cancer Society.

  9. Epstein-Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A antibodies in systemic lupus erythematosus patients.

    Science.gov (United States)

    Draborg, A H; Jørgensen, J M; Müller, H; Nielsen, C T; Jacobsen, S; Iversen, L V; Theander, E; Nielsen, L P; Houen, G; Duus, K

    2012-08-01

    We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients. We used enzyme-linked immunosorbent assay (ELISA) to investigate the prevalence of EBV early antigen diffuse (EBV-EA/D) antibodies in sera from 60 patients with SLE, 40 with scleroderma (SSc), 20 with primary Sjögren's syndrome (pSS), 20 with rheumatoid arthritis (RA), 20 healthy controls, and also subjects with various circulating autoantibodies. Samples from patients were obtained from clinics specialized within the diseases in Denmark and Sweden and samples from healthy controls were obtained from volunteers. A significant elevated titre of immunoglobulin (Ig)A, IgG, and IgM EBV-EA/D antibodies was found in SLE patients compared to healthy controls, a finding not explained by immunosuppressive treatment or disease activity. The largest difference was observed for IgA EBV-EA/D antibodies (p = 0.0013) with a seropositive rate of 58% in SLE patients and 0% in healthy controls. RA and SSc patients and individuals seropositive for anti-Scl-70 were additionally found to have elevated titres of IgA EBV-EA/D antibodies (40%, p = 0.014; 60%, p = 0.015; and 38.5%, p = 0.045, respectively). However, the titres were generally lower than in SLE patients. Our findings support an association between EBV and SLE. The elevated titre of EBV-EA/D-directed IgA antibodies found in SLE patients could suggest reactivation of EBV in epithelial cells or reinfection of epithelial cells after reactivation in B cells, indicating lack of control of the latent infection.

  10. Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.

    Directory of Open Access Journals (Sweden)

    John J Miles

    2010-11-01

    Full Text Available Despite the ∼10(18 αβ T cell receptor (TCR structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(DJ recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems.

  11. Quantitative profiling of housekeeping and Epstein-Barr virus gene transcription in Burkitt lymphoma cell lines using an oligonucleotide microarray

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    Niggli Felix K

    2006-06-01

    Full Text Available Abstract Background The Epstein-Barr virus (EBV is associated with lymphoid malignancies, including Burkitt's lymphoma (BL, and can transform human B cells in vitro. EBV-harboring cell lines are widely used to investigate lymphocyte transformation and oncogenesis. Qualitative EBV gene expression has been extensively described, but knowledge of quantitative transcription is lacking. We hypothesized that transcription levels of EBNA1, the gene essential for EBV persistence within an infected cell, are similar in BL cell lines. Results To compare quantitative gene transcription in the BL cell lines Namalwa, Raji, Akata, Jijoye, and P3HR1, we developed an oligonucleotide microarray chip, including 17 housekeeping genes, six latent EBV genes (EBNA1, EBNA2, EBNA3A, EBNA3C, LMP1, LMP2, and four lytic EBV genes (BZLF1, BXLF2, BKRF2, BZLF2, and used the cell line B95.8 as a reference for EBV gene transcription. Quantitative polymerase chain reaction assays were used to validate microarray results. We found that transcription levels of housekeeping genes differed considerably among BL cell lines. Using a selection of housekeeping genes with similar quantitative transcription in the tested cell lines to normalize EBV gene transcription data, we showed that transcription levels of EBNA1 were quite similar in very different BL cell lines, in contrast to transcription levels of other EBV genes. As demonstrated with Akata cells, the chip allowed us to accurately measure EBV gene transcription changes triggered by treatment interventions. Conclusion Our results suggest uniform EBNA1 transcription levels in BL and that microarray profiling can reveal novel insights on quantitative EBV gene transcription and its impact on lymphocyte biology.

  12. Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination.

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    Jill M Brooks

    2016-04-01

    Full Text Available Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three "first wave" proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501, as well as subdominant responses through common class I alleles (e.g. B7 and C*0304. Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that "first wave" antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design.

  13. Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus.

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    Jakovljevic, A; Andric, M; Nikolic, N; Coric, V; Krezovic, S; Carkic, J; Knezevic, A; Beljic-Ivanovic, K; Pljesa-Ercegovac, M; Miletic, M; Soldatovic, I; Radosavljevic, T; Jovanovic, T; Simic, T; Ivanovic, V; Milasin, J

    2018-01-09

    To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  14. Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

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    Sahar Shoman

    2014-09-01

    Full Text Available Epstein-Barr virus (EBV plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC, group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ and interleukin (IL-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL compared to CHC patients (6.76 pg/mL and normal controls (4.69 pg/mL. A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL compared to EBV patients (29.3 pg/mL. Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

  15. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

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    Karanikiotis, C. [424 Army General Hospital, Thessaloniki (Greece); Daniilidis, M.; Karyotis, N.; Nikolaou, A. [AHEPA Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece); Bakogiannis, C. [Hygeia Hospital, Athens (Greece); Economopoulos, T. [' Attikon' Univ. Hospital, Athens (Greece); Murray, S. [Metropolitan Hospital, Athens (Greece); Papamichael, D. [Bank of Cyprus Oncology Center, Nicosia, Cyprus (Greece); Samantas, E. [' Agii Anargiri' Cancer Hospital, Athens (Greece); Skoura, L. [' Hippokration' Hospital, Thessaloniki (Greece); Tselis, N.; Zamboglou, N. [Dept. of Radiotherapy, Offenbach Hospital (Germany); Fountzilas, G. [' Papageorgiou' Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece)

    2008-06-15

    Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

  16. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Karanikiotis, C.; Daniilidis, M.; Karyotis, N.; Nikolaou, A.; Bakogiannis, C.; Economopoulos, T.; Murray, S.; Papamichael, D.; Samantas, E.; Skoura, L.; Tselis, N.; Zamboglou, N.; Fountzilas, G.

    2008-01-01

    Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

  17. Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus

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    Hickie Ian B

    2006-01-01

    Full Text Available Abstract Background Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV infection. Methods We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Results Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene, DNAJB2 (DnaJ [Hsp40] homolog and CD99, CDK8 (cyclin-dependent kinase 8, E2F2 (E2F transcription factor 2, CDK8 (cyclin-dependent kinase 8, and ACTN2 (actinin, alpha 2, known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. Conclusion These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

  18. Epstein-Barr virus (EBV infection in Chinese children: a retrospective study of age-specific prevalence.

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    Geng Xiong

    Full Text Available BACKGROUND: Epstein-Barr Virus (EBV is a globally prevalent herpesvirus associated with infectious mononucleosis and many malignancies. The survey on EBV prevalence appears to be important to study EBV-related diseases and determine when to administer prophylactic vaccine. The purpose of this retrospective study was to collect baseline information about the prevalence of EBV infection in Chinese children. METHODOLOGY/PRINCIPAL FINDING: We collected 1778 serum samples from healthy children aged 0 to 10, who were enrolled in conventional health and nutrition examinations without any EBV-related symptom in 2012 and 2013 in North China (n = 973 and South China (n = 805. We detected four EBV-specific antibodies, i.e., anti-VCA-IgG and IgM, anti-EBNA-IgG and anti-EA-IgG, by ELISA, representing all of the phases of EBV infection. The overall EBV seroprevalence in samples from North and South China were 80.78% and 79.38% respectively. The EBV seropositivity rates dropped slightly at age 2, and then increased gradually with age. The seroprevalence became stabilized at over 90% after age 8. In this study, the seroprevalence trends between North and South China showed no difference (P>0.05, and the trends of average antibody concentrations were similar as well (P>0.05. CONCLUSIONS/SIGNIFICANCE: EBV seroprevalence became more than 50% before age 3 in Chinese children, and exceed 90% after age 8. This study can be helpful to study the relationship between EBV and EBV-associated diseases, and supportive to EBV vaccine development and implementation.

  19. Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat

    International Nuclear Information System (INIS)

    Kenney, S.; Kamine, J.; Markovitz, D.; Fenrick, R.; Pagano, J.

    1988-01-01

    Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, the authors demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses

  20. Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

    Science.gov (United States)

    Lawson, James S; Salmons, Brian; Glenn, Wendy K

    2018-01-01

    Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. MMTV and human breast cancer-the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer-the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer-the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer-the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

  1. Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

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    David H. Dreyfus

    2017-01-01

    Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

  2. Routine detection of Epstein-Barr virus specific T-cells in the peripheral blood by flow cytometry

    Science.gov (United States)

    Crucian, B. E.; Stowe, R. P.; Pierson, D. L.; Sams, C. F.

    2001-01-01

    The ability to detect cytomegalovirus-specific T-cells (CD4(+)) in the peripheral blood by flow cytometry has been recently described by Picker et al. In this method, cells are incubated with viral antigen and responding (cytokine producing) T-cells are then identified by flow cytometry. To date, this technique has not been reliably used to detect Epstein-Barr virus (EBV)-specific T-cells primarily due to the superantigen/mitogenic properties of the virus which non-specifically activate T-cells. By modifying culture conditions under which the antigens are presented, we have overcome this limitation and developed an assay to detect and quantitate EBV-specific T-cells. The detection of cytokine producing T-cells by flow cytometry requires an extremely strong signal (such as culture in the presence of PMA and ionomycin). Our data indicate that in modified culture conditions (early removal of viral antigen) the non-specific activation of T-cells by EBV is reduced, but antigen presentation will continue uninhibited. Using this method, EBV-specific T-cells may be legitimately detected using flow cytometry. No reduction in the numbers of antigen-specific T-cells was observed by the early removal of target antigen when verified using cytomegalovirus antigen (a virus with no non-specific T-cell activation properties). In EBV-seropositive individuals, the phenotype of the EBV-specific cytokine producing T-cells was evaluated using four-color flow cytometry and found to be CD45(+), CD3(+), CD4(+), CD45RA(-), CD69(+), CD25(-). This phenotype indicates the stimulation of circulating previously unactivated memory T-cells. No cytokine production was observed in CD4(+) T-cells from EBV-seronegative individuals, confirming the specificity of this assay. In addition, the use of four color cytometry (CD45, CD3, CD69, IFNgamma/IL-2) allows the total quantitative assessment of EBV-specific T-cells while monitoring the interference of EBV non-specific mitogenic activity. This method may

  3. Fate and expression of the deleted mitochondrial DNA differ between human heteroplasmic skin fibroblast and Epstein-Barr virus-transformed lymphocyte cultures.

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    Bourgeron, T; Chretien, D; Rötig, A; Munnich, A; Rustin, P

    1993-09-15

    We report on the variant phenotypic expression of mitochondrial genotypes in cultured skin fibroblasts and Epstein-Barr virus-transformed lymphocyte cultures from a patient with Pearson syndrome (McKusick no. 260560). Both cell types harbored a heteroplasmic population of normal and deleted mtDNA molecules. The deletion encompassed five tRNA genes and seven genes encoding subunits of cytochrome c oxidase, complex I, and ATPase. Patient skin fibroblasts and lymphocytes harbored 60 and 80% of deleted mtDNA molecules, respectively, and initially displayed defective respiratory chain activities. In both cases, there was a progressive recovery of respiratory chain activities during in vitro cell proliferation. In cultured skin fibroblasts, the loss of the deleted mtDNA molecules accounted for the recovery of normal respiratory chain activities. These features were prevented by allowing respiratory chain-deficient cells to grow in the presence of uridine (200 microM). In Epstein-Barr virus-transformed lymphocytes containing 60% of deleted mtDNA, the recovery of respiratory chain activities was attributable to an increase in the mtRNA translation efficiency rather than to an increased content in mtDNA or mtRNA. The present study suggests that the variant cellular responses to abnormal mitochondrial genotypes might contribute to the tissue-specific expression of mitochondrial disorders in vivo.

  4. Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

    Science.gov (United States)

    Menter, T; Schlageter, M; Bastian, L; Haberthür, R; Rätz Bravo, A E; Tzankov, A

    2014-03-01

    Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists. Copyright © 2013 John Wiley & Sons, Ltd.

  5. The Epstein-Barr virus DNA load in the peripheral blood of transplant recipients does not accurately reflect the burden of infected cells.

    Science.gov (United States)

    Fink, Susanne; Tsai, Ming-Han; Schnitzler, Paul; Zeier, Martin; Dreger, Peter; Wuchter, Patrick; Bulut, Olcay C; Behrends, Uta; Delecluse, Henri-Jacques

    2017-01-01

    Transplant recipients frequently exhibit an increased Epstein-Barr virus (EBV) load in the peripheral blood. Here, we quantitated the EBV-infected cells in the peripheral blood of these patients and defined the mode of viral infection, latent or lytic. These data indicated that there is no strong correlation between the number of infected cells and the EBV load (EBVL). This can be explained by a highly variable number of EBV copies per infected cell and by lytic replication in some cells. The plasma of these patients did not contain any free infectious viruses, but contained nevertheless EBV DNA, sometimes in large amounts, that probably originates from cell debris and contributed to the total EBVL. Some of the investigated samples carried a highly variable number of infected cells in active latency, characterized by an expression of the Epstein-Barr nuclear antigens (EBNA2) protein. However, a third of the samples expressed neither EBNA2 nor lytic proteins. Patients with an increased EBVL represent a heterogeneous group of patients whose infection cannot be characterized by this method alone. Precise characterization of the origin of an increased EBVL, in particular, in terms of the number of EBV-infected cells, requires additional investigations including the number of EBV-encoded small RNA-positive cells. © 2016 Steunstichting ESOT.

  6. Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus.

    Science.gov (United States)

    Delecluse, Henri-Jacques; Feederle, Regina; Behrends, Uta; Mautner, Josef

    2008-12-01

    Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The 'mini-EBVs', for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might

  7. Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

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    Iva Polakovicova

    2018-04-01

    Full Text Available Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori, a bacterium present in half of the world population; or by Epstein-Barr virus (EBV, a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs, influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA, a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1 which are

  8. Human Herpesvirus 8-Negative and Epstein-Barr Virus-Positive Effusion-Based Lymphoma in a Patient with Human Immunodeficiency Virus

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    Jung-Woo Choi

    2015-09-01

    Full Text Available A 39-year-old man infected with human immunodeficiency virus (HIV was admitted to our hospital because of sudden onset of chest pain. Chest radiography revealed pneumothorax of the right lung. Computed tomographic scans disclosed a 5.8-cm-sized emphysematous bulla in the right middle lobe of the lung. Histologically, the wedge-resected lung showed medium to large atypical cells within the bullous cavity of the Pneumocystis jirovecii pneumonia, without solid mass formation. These atypical cells were confirmed to be large B-cell lymphoma, Epstein-Barr virus–positive and human herpesvirus 8–negative. Therefore, this case was not diagnosed as primary effusion lymphoma, but effusion-based lymphoma arising in an emphysematous cavity of an HIV-infected patient. This type of effusion-based lymphoma has never been reported, and, although rare, it should be noted in order to clinically diagnose this lymphoma.

  9. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell--depleted SCT

    NARCIS (Netherlands)

    van Esser, J W; van der Holt, B; Meijer, E; Niesters, H G; Trenschel, R; Thijsen, S F; van Loon, A M; Frassoni, F; Bacigalupo, A; Schaefer, U W; Osterhaus, A D; Gratama, J W; Löwenberg, B; Verdonck, L F; Cornelissen, J J

    2001-01-01

    Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and

  10. Epstein-Barr virus-positive post-transplant lymphoproliferative disorder of the central nervous system, after renal transplantation with a discrepancy in viral load between peripheral blood and cerebrospinal fluid

    NARCIS (Netherlands)

    Boersma, Marijke Nynke; van der Zanden, Adri; Laverman, Gozewijn Dirk; Sanders, Jan Stephan; de Vries, Peter Alexander Marcel

    2012-01-01

    A 43-year-old female developed an EpsteinBarr virus (EBV)-positive post-transplant lymphoproliferative disorder (PTLD) in the central nervous system (CNS), 14 years after renal transplantation. One year prior to presentation, the patients treatment regimen was altered from cyclosporine,

  11. Direct Epstein-Barr virus (EBV) typing on peripheral blood mononuclear cells: no association between EBV type 2 infection or superinfection and the development of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    van Baarle, D.; Hovenkamp, E.; Kersten, M. J.; Klein, M. R.; Miedema, F.; van Oers, M. H.

    1999-01-01

    In the literature, a correlation has been suggested between the occurrence of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (NHL) and Epstein-Barr virus (EBV) type 2 infection. To further investigate a possible role for EBV type 2 infection in the development of AIDS-NHL,

  12. Evaluation of Novel Acyclic Nucleoside Phosphonates against Human and Animal Gammaherpesviruses Revealed an Altered Metabolism of Cyclic Prodrugs upon Epstein-Barr Virus Reactivation in P3HR-1 Cells

    Czech Academy of Sciences Publication Activity Database

    Coen, N.; Duraffour, S.; Naesens, L.; Krečmerová, Marcela; Van Den Oord, J.; Snoeck, R.; Andrei, G.

    2013-01-01

    Roč. 87, č. 22 (2013), s. 12422-12432 ISSN 0022-538X R&D Projects: GA MPO FR-TI4/625 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate * gammaherpesvirus * Epstein-Barr virus * Kaposi's sarcoma * HPMP-5-azaC * cidofovir Subject RIV: EE - Microbiology, Virology Impact factor: 4.648, year: 2013

  13. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    van Baarle, D; Hovenkamp, E; Callan, M F; Wolthers, K C; Kostense, S; Tan, L C; Niesters, H G; Osterhaus, A D; McMichael, A J; van Oers, M H; Miedema, F

    2001-01-01

    Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of

  14. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    D. van Baarle (Debbie); F. Miedema (Frank); E. Hovenkamp (Egbert); M.F.C. Callan (Margareth); K.C. Wolthers (Katja); S. Kostense; L.C. Tan; H.G.M. Niesters (Bert); A.D.M.E. Osterhaus (Albert); A.J. McMichael (Andrew); M.H.J. van Oers (Marinus)

    2001-01-01

    textabstractAcquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or

  15. Epstein-Barr virus in oral hairy leukoplakia scrapes: identification by PCR Vírus Epstein-Barr em esfregaço de leucoplasia pilosa oral: identificação por PCR

    Directory of Open Access Journals (Sweden)

    Tatiana Lucianelli Komatsu

    2005-12-01

    Full Text Available Oral hairy leukoplakia (OHL is a lesion associated with a compromised immune system, and its diagnosis is determined by the demonstration of the presence of Epstein-Barr virus (EBV in lesional tissue. The purpose of this article was to develop a simple technique to help the diagnosis of OHL, using PCR as an alternative technique to evidence EBV in scrapings. DNA samples were obtained by scraping the lateral border of the tongue of 38 adult patients: 29 HIV-positive patients (4 with clinical evidence of OHL; 4 with history of OHL, but without lesion at the moment the samples were collected; and 21 without clinical evidence of OHL, and 9 healthy volunteers for the control group. DNA was extracted from scrapes and amplified by PCR using specific primers for EBV. Of the 29 cases of HIV-positive patients, 22 (75.86% were positive for EBV: 2 patients with clinical evidence of OHL, 4 patients with history of OHL, but without lesion at the moment the samples were collected, and 16 patients without clinical evidence of OHL. In the control group, samples of 5 (55.56% healthy volunteers presented amplification for EBV. We concluded that the use of PCR in oral scrapes suggests a high sensitivity but low specificity for the diagnosis of OHL.A leucoplasia pilosa (LP é uma lesão associada ao comprometimento do sistema imune e seu diagnóstico é determinado pela demonstração da presença do vírus Epstein-Barr (EBV no tecido lesionado. O objetivo deste trabalho foi desenvolver uma metodologia simples para auxiliar no diagnóstico da LP, utilizando-se a técnica da PCR como uma alternativa para evidenciar o EBV em esfregaços da lesão. Amostras de DNA foram obtidas por meio de raspado de borda lateral de língua, de 38 pacientes adultos, sendo estes: 29 pacientes HIV positivos (4 com evidência clínica de leucoplasia pilosa, 4 que haviam apresentado LP previamente, mas não no momento da coleta, e 21 sem evidência clínica de leucoplasia pilosa e 9

  16. Hodgkin lymphoma, HIV, and Epstein-Barr virus in Malawi: Longitudinal results from the Kamuzu Central Hospital Lymphoma study.

    Science.gov (United States)

    Westmoreland, Katherine D; Stanley, Christopher C; Montgomery, Nathan D; Kaimila, Bongani; Kasonkanji, Edwards; El-Mallawany, Nader Kim; Wasswa, Peter; Mtete, Idah; Butia, Mercy; Itimu, Salama; Chasela, Mary; Mtunda, Mary; Chikasema, Maria; Makwakwa, Victor; Kampani, Coxcilly; Dhungel, Bal M; Sanders, Marcia K; Krysiak, Robert; Tomoka, Tamiwe; Liomba, N George; Dittmer, Dirk P; Fedoriw, Yuri; Gopal, Satish

    2017-05-01

    Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are prevalent. We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma. Among 31 patients with confirmed cHL, the median age was 19 years (range, 2-51 years) and 22 (71%) were male. Sixteen patients (52%) had stage III/IV, 25 (81%) B symptoms, and 16 (52%) performance status impairment. Twenty-three patients (74%) had symptoms >6 months, and 11 of 29 (38%) had received empiric antituberculosis treatment. Anemia was common with median hemoglobin 8.2 g/dL (range, 3.1-17.1 g/dL), which improved during treatment. No children and 5 of 15 adults (33%) were HIV+. All HIV+ patients were on antiretroviral therapy for a median 15 months (range, 2-137 months), with median CD4 count 138 cells/μL (range, 23-329 cells/μL) and four (80%) having undetectable HIV. EBV was present in 18 of 24 (75%) tumor specimens, including 14 of 20 (70%) HIV- and 4 of 4 (100%) HIV+. Baseline plasma EBV DNA was detected in 25 of 28 (89%) patients, with median viral load 4.7 (range, 2.0-6.7) log 10 copies/mL, and subsequently declined in most patients. At 12 months, overall survival was 75% (95% confidence interval [CI], 55%-88%) and progression-free survival 65% (95% CI, 42%-81%). Baseline plasma EBV DNA and persistent viremia during treatment were associated with poorer outcomes. cHL in Malawi is characterized by delayed diagnosis and advanced disease. Most cases were EBV associated and one-third of adults were HIV+. Despite resource limitations, 12-month outcomes were good. © 2016 Wiley Periodicals, Inc.

  17. Interferon-γ-inducible protein 16 (IFI16) is required for the maintenance of Epstein-Barr virus latency.

    Science.gov (United States)

    Pisano, Gina; Roy, Arunava; Ahmed Ansari, Mairaj; Kumar, Binod; Chikoti, Leela; Chandran, Bala

    2017-11-13

    Epstein-Barr virus (EBV) exhibits both lytic and latent (Lat. I, II, and III) phases in an infected individual. It's during the latent phase of EBV that all EBV-associated cancers, including Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease arise. Interferon-γ-inducible protein 16 (IFI16) is a well-established innate immune sensor and viral transcriptional regulator involved in response to invading DNA viruses. During latency, IFI16 remains in the nucleus, in part bound to the EBV genome; however, neither its role in EBV lytic cycle or latency has been established. Short interfering RNA against IFI16 and IFI16 overexpression were used to identify the role of IFI16 in the maintenance of EBV latency I. We also studied how induction of the lytic cycle affected IFI16 using the EBV positive, latently infected Akata or MUTU-1 cell lines. Akata cells were induced with TPA and MUTU-1 cells with TGF-β up to 96 h and changes in IFI16 protein were analyzed by Western blotting and immunofluorescence microscopy. To assess the mechanism of IFI16 decrease, EBV DNA replication and late lytic transcripts were blocked using the viral DNA polymerase inhibitor phosphonoacetic acid. Knockdown of IFI16 mRNA by siRNA resulted in enhanced levels of EBV lytic gene expression from all temporal gene classes, as well as an increase in the total EBV genome abundance, whereas overexpression of exogenous IFI16 reversed these effects. Furthermore, 96 h after induction of the lytic cycle with either TPA (Akata) or TGF-β (MUTU-1), IFI16 protein levels decreased up to 80% as compared to the EBV-negative cell line BJAB. Reduction in IFI16 was observed in cells expressing EBV lytic envelope glycoprotein. The decreased levels of IFI16 protein do not appear to be dependent on late lytic transcripts of EBV but suggest involvement of the immediate early, early, or a combination of both gene classes. Reduction of IFI16 protein levels following lytic cycle induction, as well

  18. Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection.

    Science.gov (United States)

    Weiss, Eric R; Lamers, Susanna L; Henderson, Jennifer L; Melnikov, Alexandre; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Nusbaum, Chad; Luzuriaga, Katherine

    2018-01-15

    Over 90% of the world's population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time ( P diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral populations is a key step in this process, as is the expansion of intrahost genomic variation during infection. We report full-length EBV genomes sequenced from the blood and oral wash of 10 individuals early in primary infection and during convalescence. Our data demonstrate considerable diversity within the pool of circulating EBV strains, as well as within individual patients

  19. Comparison of Abbott Architect®, Siemens Immulite®, and Diasorin Liaison®for determination of Epstein-Barr virus serological diagnosis.

    Science.gov (United States)

    François, Catherine; Segard, Christine; Bouvier, Maryline; Stefanski, Martine; Pannier, Christine; Zawadzki, Patricia; Roussel, Catherine; Hecquet, Denise; Duverlie, Gilles; Brochot, Etienne; Castelain, Sandrine

    2018-02-01

    This study compared the performance of 3 automated immunoassays, Architect ® (Abbott), Immulite ® (Siemens) and Liaison ® (Diasorin), for Epstein-Barr virus (EBV) serology. Ninety-one serum samples collected in Amiens University Hospital were analyzed for the presence of Viral Capsid Antigen (VCA) IgG and IgM and Epstein-Barr Nuclear Antigen (EBNA) IgG. The agreement between the 3 assays was calculated for each marker individually and for determination of the EBV profile, based on interpretation of the combination of these 3 EBV markers. Although similar results were obtained with Architect ® and Liaison ® , several discordant results were observed with Immulite ® , particularly for EBNA IgG. A large number of EBNA IgG-positive results were observed, which interfered with interpretation of the EBV profile. In contrast, Immulite ® performed similarly to the 2 other assays for detection of VCA IgM. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Systematic review and meta-analysis of the sero-epidemiological association between Epstein Barr virus and multiple sclerosis.

    Science.gov (United States)

    Almohmeed, Yahya H; Avenell, Alison; Aucott, Lorna; Vickers, Mark A

    2013-01-01

    A role for Epstein Barr virus (EBV) in multiple sclerosis (MS) has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MS patients compared to controls, but many studies have since been published, and there is a need to apply more rigorous systematic review methods. We examined the link between EBV and MS by conducting a systematic review and meta-analysis of case-control and cohort studies that examined the prevalence of anti-EBV antibodies in the serum of cases and controls. We searched Medline and Embase databases from 1960 to 2012, with no language restriction. The Mantel-Haenszel odds ratios (OR) for anti-EBV antibodies sero-positivity were calculated, and meta-analysis conducted. Quality assessment was performed using a modified version of the Newcastle Ottawa scale. Thirty-nine studies were included. Quality assessment found most studies reported acceptable selection and comparability of cases and controls. However the majority had poor reporting of ascertainment of exposure. Most studies found a higher sero-prevalence of anti-EBNA IgG and anti-VCA IgG in cases compared to controls. The results for anti-EA IgG were mixed with only half the studies finding a higher sero-prevalence in cases. The meta-analysis showed a significant OR for sero-positivity to anti-EBNA IgG and anti-VCA IgG in MS cases (4.5 [95% confidence interval (CI) 3.3 to 6.6, p<0.00001] and 4.5 [95% CI 2.8 to 7.2, p<0.00001] respectively). However, funnel plot examination suggested publication bias for the reporting of the anti-EBNA IgG. No significant difference in the OR for sero-positivity to anti-EA IgG was found (1.4 [95% CI 0.9 to 2.1, p = 0.09]). These findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of laboratory analyses.

  1. Systematic review and meta-analysis of the sero-epidemiological association between Epstein Barr virus and multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Yahya H Almohmeed

    Full Text Available BACKGROUND: A role for Epstein Barr virus (EBV in multiple sclerosis (MS has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MS patients compared to controls, but many studies have since been published, and there is a need to apply more rigorous systematic review methods. METHODOLOGY/PRINCIPAL FINDINGS: We examined the link between EBV and MS by conducting a systematic review and meta-analysis of case-control and cohort studies that examined the prevalence of anti-EBV antibodies in the serum of cases and controls. We searched Medline and Embase databases from 1960 to 2012, with no language restriction. The Mantel-Haenszel odds ratios (OR for anti-EBV antibodies sero-positivity were calculated, and meta-analysis conducted. Quality assessment was performed using a modified version of the Newcastle Ottawa scale. Thirty-nine studies were included. Quality assessment found most studies reported acceptable selection and comparability of cases and controls. However the majority had poor reporting of ascertainment of exposure. Most studies found a higher sero-prevalence of anti-EBNA IgG and anti-VCA IgG in cases compared to controls. The results for anti-EA IgG were mixed with only half the studies finding a higher sero-prevalence in cases. The meta-analysis showed a significant OR for sero-positivity to anti-EBNA IgG and anti-VCA IgG in MS cases (4.5 [95% confidence interval (CI 3.3 to 6.6, p<0.00001] and 4.5 [95% CI 2.8 to 7.2, p<0.00001] respectively. However, funnel plot examination suggested publication bias for the reporting of the anti-EBNA IgG. No significant difference in the OR for sero-positivity to anti-EA IgG was found (1.4 [95% CI 0.9 to 2.1, p = 0.09]. CONCLUSION/SIGNIFICANCE: These findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of

  2. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

    Science.gov (United States)

    Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

    2015-02-14

    To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real

  3. Proteomics and Transcriptomics of BJAB Cells Expressing the Epstein-Barr Virus Noncoding RNAs EBER1 and EBER2.

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    Genaro Pimienta

    Full Text Available In Epstein-Barr virus (EBV latent infection, the EBV-encoded RNAs EBER1 and EBER2 accumulate in the host cell nucleus to ~10(6 copies. While the expression of EBERs in cell lines is associated with transformation, a mechanistic explanation of their roles in EBV latency remains elusive. To identify EBER-specific gene expression features, we compared the proteome and mRNA transcriptome from BJAB cells (an EBV-negative B lymphoma cell line stably transfected with an empty plasmid or with one carrying both EBER genes. We identified ~1800 proteins with at least 2 SILAC pair measurements, of which only 8 and 12 were up- and downregulated ≥ 2-fold, respectively. One upregulated protein was PIK3AP1, a B-cell specific protein adapter known to activate the PI3K-AKT signaling pathway, which regulates alternative splicing and translation in addition to its pro-survival effects. In the mRNA-seq data, the mRNA levels for some of the proteins changing in the SILAC data did not change. We instead observed isoform switch events. We validated the most relevant findings with biochemical assays. These corroborated the upregulation of PIK3AP1 and AKT activation in BJAB cells expressing high levels of both EBERs and EBNA1 (a surrogate of Burkitt's lymphoma EBV latency I relative to those expressing only EBNA1. The mRNA-seq data in these cells showed multiple upregulated oncogenes whose mRNAs are enriched for 3´-UTR AU-rich elements (AREs, such as ccl3, ccr7, il10, vegfa and zeb1. The CCL3, CCR7, IL10 and VEGFA proteins promote cell proliferation and are associated with EBV-mediated lymphomas. In EBV latency, ZEB1 represses the transcription of ZEBRA, an EBV lytic phase activation factor. We previously found that EBER1 interacts with AUF1 in vivo and proposed stabilization of ARE-containing mRNAs. Thus, the ~10(6 copies of EBER1 may promote not only cell proliferation due to an increase in the levels of ARE-containing genes like ccl3, ccr7, il10, and vegfa, but

  4. Aged-associated cytomegalovirus and Epstein-Barr virus reactivation and cytomegalovirus relationship with the frailty syndrome in older women.

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    Ronaldo Luis Thomasini

    Full Text Available Immunosenescence is an age-related reduction of immune system activity that can be associated with frailty. This study aimed to compare cytomegalovirus (CMV and Epstein-Barr virus (EBV reactivations (based on viremias between young and elderly women who had a chronic CMV and/or EBV infection (i.e., an IgG+ serostatus without an acute infection (i.e., an IgM- serostatus, and among the elderly group categorized according to frailty status. DNA was extracted from plasma using standard protocols and serostatus was determined by enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction analyses for CMV and EBV were carried out and viral loads were determined. Among elderly women (n = 71, 59% were positive for CMV, in contrast to only 8% of young women (n = 73. Elderly women classified as frail, pre-frail, and non-frail presented 82%, 56%, and 48% positivity for CMV, respectively. Frequency and viral load were significantly higher in the elderly group vs. the young group (p < 0.0001 and p = 0.01, respectively and in elderly with frailty vs. those without frailty (p = 0.007 and p = 0.03, respectively. The frequency of CMV reactivation presented odds ratios of 11.77 for aging and 6.13 for frailty, and relative risks of 5.39 for aging and 1.93 for frailty. EBV was detected in 30% of the elderly women and 15% of the young women (p = 0.04; however, the viral load did not significantly differ between the two age groups. The frequency of EBV reactivation presented odds ratios of 2.36 for aging and 2.90 for frailty, and relative risks of 1.96 for aging and 2.12 for frailty. However, no difference in EBV viral load among the frailty status subgroups was found. In conclusion, the frequency of CMV reactivation was associated with aging and ongoing frailty, whereas the frequency of EBV reactivation was associated only with aging.

  5. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis.

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    Daniela F Angelini

    Full Text Available It has long been known that multiple sclerosis (MS is associated with an increased Epstein-Barr virus (EBV seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk. This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis, although the mechanisms are debated. This study was designed to assess the prevalence and magnitude of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A and lytic (BZLF-1, BMLF-1 antigens in relapsing-remitting MS patients (n = 113 and healthy donors (HD (n = 43 and to investigate whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, lytic antigen-specific CD8+ T cell responses were detected in fewer untreated inactive MS patients than in active MS patients and HD while the frequency of CD8+ T cells specific for EBV lytic and latent antigens was higher in active and inactive MS patients, respectively. In contrast, the CD8+ T cell response to cytomegalovirus did not differ between HD and MS patients, irrespective of the disease phase. Marked differences in the prevalence of EBV-specific CD8+ T cell responses were observed in patients treated with interferon-β and natalizumab, two licensed drugs for relapsing-remitting MS. Longitudinal studies revealed expansion of CD8+ T cells specific for EBV lytic antigens during active disease in untreated MS patients but not in relapse-free, natalizumab-treated patients. Analysis of post-mortem MS brain samples showed expression of the EBV lytic protein BZLF-1 and interactions between cytotoxic CD8+ T cells and EBV lytically infected plasma cells in inflammatory white matter lesions and meninges. We therefore propose that inability to control EBV infection during inactive MS could set the stage for intracerebral viral reactivation and disease relapse.

  6. Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1

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    Wang Pu

    2010-10-01

    Full Text Available Abstract The Epstein-Barr Virus (EBV Nuclear Antigen 1 (EBNA1 protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP, regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP combined with massively parallel deep-sequencing (ChIP-Seq was used to identify cellular sites bound by EBNA1. Sites identified by ChIP-Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A consensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, suggesting that some of these sites are indirectly bound by EBNA1. EBNA1 also bound close to the transcriptional start sites of a large number of cellular genes, including HDAC3, CDC7, and MAP3K1, which we show are positively regulated by EBNA1. EBNA1 binding sites were enriched in some repetitive elements, especially LINE 1 retrotransposons, and had weak correlations with histone modifications and ORC binding. We conclude that EBNA1 can interact with a large number of cellular genes and chromosomal loci in latently infected cells, but that these sites are likely to represent a complex ensemble of direct and indirect EBNA

  7. Nasopharyngeal Epstein-Barr Virus Load: An Efficient Supplementary Method for Population-Based Nasopharyngeal Carcinoma Screening.

    Science.gov (United States)

    Chen, Yufeng; Zhao, Weilin; Lin, Longde; Xiao, Xue; Zhou, Xiaoying; Ming, Huixin; Huang, Tingting; Liao, Jian; Li, Yancheng; Zeng, Xiaoyun; Huang, Guangwu; Ye, Weimin; Zhang, Zhe

    2015-01-01

    Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers ≥ 1:5 were defined as high-risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening

  8. TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation.

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    Hannah Greenfeld

    2015-05-01

    Full Text Available The Epstein-Barr virus (EBV encoded oncoprotein Latent Membrane Protein 1 (LMP1 signals through two C-terminal tail domains to drive cell growth, survival and transformation. The LMP1 membrane-proximal TES1/CTAR1 domain recruits TRAFs to activate MAP kinase, non-canonical and canonical NF-kB pathways, and is critical for EBV-mediated B-cell transformation. TRAF1 is amongst the most highly TES1-induced target genes and is abundantly expressed in EBV-associated lymphoproliferative disorders. We found that TRAF1 expression enhanced LMP1 TES1 domain-mediated activation of the p38, JNK, ERK and canonical NF-kB pathways, but not non-canonical NF-kB pathway activity. To gain insights into how TRAF1 amplifies LMP1 TES1 MAP kinase and canonical NF-kB pathways, we performed proteomic analysis of TRAF1 complexes immuno-purified from cells uninduced or induced for LMP1 TES1 signaling. Unexpectedly, we found that LMP1 TES1 domain signaling induced an association between TRAF1 and the linear ubiquitin chain assembly complex (LUBAC, and stimulated linear (M1-linked polyubiquitin chain attachment to TRAF1 complexes. LMP1 or TRAF1 complexes isolated from EBV-transformed lymphoblastoid B cell lines (LCLs were highly modified by M1-linked polyubiqutin chains. The M1-ubiquitin binding proteins IKK-gamma/NEMO, A20 and ABIN1 each associate with TRAF1 in cells that express LMP1. TRAF2, but not the cIAP1 or cIAP2 ubiquitin ligases, plays a key role in LUBAC recruitment and M1-chain attachment to TRAF1 complexes, implicating the TRAF1:TRAF2 heterotrimer in LMP1 TES1-dependent LUBAC activation. Depletion of either TRAF1, or the LUBAC ubiquitin E3 ligase subunit HOIP, markedly impaired LCL growth. Likewise, LMP1 or TRAF1 complexes purified from LCLs were decorated by lysine 63 (K63-linked polyubiqutin chains. LMP1 TES1 signaling induced K63-polyubiquitin chain attachment to TRAF1 complexes, and TRAF2 was identified as K63-Ub chain target. Co-localization of M1- and K63

  9. Plasma Epstein-Barr virus DNA for pediatric Burkitt lymphoma diagnosis, prognosis and response assessment in Malawi.

    Science.gov (United States)

    Westmoreland, Katherine D; Montgomery, Nathan D; Stanley, Christopher C; El-Mallawany, Nader Kim; Wasswa, Peter; van der Gronde, Toon; Mtete, Idah; Butia, Mercy; Itimu, Salama; Chasela, Mary; Mtunda, Mary; Kampani, Coxcilly; Liomba, N George; Tomoka, Tamiwe; Dhungel, Bal M; Sanders, Marcia K; Krysiak, Robert; Kazembe, Peter; Dittmer, Dirk P; Fedoriw, Yuri; Gopal, Satish

    2017-06-01

    Point-of-care tools are needed in sub-Saharan Africa (SSA) to improve pediatric Burkitt lymphoma (BL) diagnosis and treatment. We evaluated plasma Epstein-Barr virus (pEBV) DNA as a pediatric BL biomarker in Malawi. Prospectively enrolled children with BL were compared to classical Hodgkin lymphoma (cHL) and nonlymphoma diagnoses. Pediatric BL patients received standardized chemotherapy and supportive care. pEBV DNA was measured at baseline, mid-treatment, and treatment completion. Of 121 assessed children, pEBV DNA was detected in 76/88 (86%) with BL, 16/17 (94%) with cHL, and 2/16 (12%) with nonlymphoma, with proportions higher in BL versus nonlymphoma (p < 0.001) and similar in BL versus cHL (p = 0.69). If detected, median pEBV DNA was 6.1 log 10 copies/mL for BL, 4.8 log 10 copies/mL for cHL, and 3.4 log 10 copies/mL for nonlymphoma, with higher levels in BL versus cHL (p = 0.029), and a trend toward higher levels in BL versus nonlymphoma (p = 0.062). pEBV DNA declined during treatment in the cohort overall and increased in several children before clinical relapse. Twelve-month overall survival was 40% in the cohort overall, and for children with baseline pEBV detected, survival was worse if baseline pEBV DNA was ≥6 log 10 copies/mL versus <6 log 10 copies/mL (p = 0.0002), and also if pEBV DNA was persistently detectable at mid-treatment versus undetectable (p = 0.041). Among children with baseline pEBV DNA detected, viremia was the only significant risk factor for death by 12 months in multivariate analyses (adjusted hazard ratio 1.35 per log 10 copies/mL, 95% CI 1.04-1.75, p = 0.023). Quantitative pEBV DNA has potential utility for diagnosis, prognosis, and response assessment for pediatric BL in SSA. © 2017 UICC.

  10. Prevalence and molecular profiling of Epstein Barr virus (EBV among healthy blood donors from different nationalities in Qatar.

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    Maria K Smatti

    Full Text Available The Epstein-Barr virus (EBV is the causative agent of infectious mononucleosis. EBV is highly prevalent lymphotropic herpesvirus and has been linked to several malignancies. Transmission is generally by oral secretions, but can be through blood transfusions and organ transplantations. This study aimed to determine the seroprevalence, viremia rates, and circulating genotypes of EBV in healthy blood donors in Qatar.Blood samples from 673 blood donors of different nationalities residing in Qatar (mainly Qatar, Egypt, Syria, Jordan, Pakistan, and India were collected and tested for anti-EBV capsid (VCA; IgG & IgM, nuclear (EBNA; IgG, and early (EA-D; IgG antigens. Avidity testing was determined when active infection was suspected. DNA was extracted from the buffy coat and subjected to EBV-DNA quantification using qRT-PCR. Genotyping was performed using nested-PCR targeting EBV-EBNA2 gene, and phylogeny by sequence analysis of the LMP-1 gene.97.9% (673/659 of the samples were seropositive as indicated by the presence VCA-IgG, while 52.6% (354/673 had detectible EBV-DNA. EBV seroprevalence and viremia rates increased significantly with age. Genotyping of 51 randomly selected samples showed predominance of Genotype 1 (72.5%, 37/51 as compared to genotype 2 (3.5%, and mixed infections were detected in 4% of the samples. Sub-genotyping for these samples revealed that the Mediterranean strain was predominant (65.3%, followed by B95.8 prototype and North Carolina strains (12.2% each, and China1 strain (6%.As a first study to evaluate EBV infection in highly diverse population in Qatar, where expatriates represent more than 85% of the population, our results indicated high seroprevalence and viremia rate of EBV in different nationalities, with genotype 1 and Mediterranean strain being predominant. Clinical significance of these finding have not been investigated and shall be evaluated in future studies.

  11. Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus.

    Directory of Open Access Journals (Sweden)

    Maria Raffaella Petrara

    Full Text Available Although monotherapy (mART effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV is unclear.This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA were quantified by real-time PCR. Markers of T-(CD3+CD8+CD38+ and B-(CD19+CD80/86+ and CD19+CD10-CD21lowCD27+ cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt]DNA or by ELISA (LPS and sCD14. EBV was typed and quantified by multiplex real-time PCR.At baseline, no differences were found between mART and cART groups. Three (10% mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T- and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively. Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001.Long-term mART is associated with higher levels of T- and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection.

  12. Epstein-Barr virus associated central nervous system leiomyosarcoma occurring after renal transplantation: case report and review of the literature; Leiomyosarcome primitif du systeme nerveux central associe au virus d'Epstein-Barr (EBV) et survenu apres transplantation renale: a propos d'un cas et revue de la litterature

    Energy Technology Data Exchange (ETDEWEB)

    Tahri, A.; Noel, G.; Feuvret, L.; Jauffret, E.; Brun, B.; Mazeron, J.J.; Baillet, F. [Centre des Tumeurs, Groupe Hospitalier Universitaire Pitie-Salpetriere, 75 - Paris (France); Feuvret, L. [Centre de Protontherapie d' Orsay, 91 (France); Figuerella-Branger, D. [Hopital de la Timone, Service d' Anatomopathologie, 13 - Marseille (France); Goncalves, A. [Institut Paoli-Calmettes, Service d' Oncologie Medicale, 13 - Marseille (France)

    2003-10-01

    Central nervous system leiomyosarcomas are extremely rare, however, they became more frequent among immuno-deficient patients, either in a patients infected with human immunodeficiency virus (HIV), or after organ transplantation. The data of the literature indicate that the infection by Epstein-Barr virus (EBV) plays a causal role in the development of these tumours but its precise role in the onco-genesis remains unresolved. We report a new case of EBV associated leiomyosarcoma of the left cavernous sinus occurring after renal transplantation. The epidemiological, clinical, pathological and therapeutic characteristics of these tumours are discussed. (authors)

  13. Prevalence of Polyoma BK Virus (BKPyV), Epstein-Barr Virus (EBV) and Human Papilloma Virus (HPV) in Oropharyngeal Cancer.

    Science.gov (United States)

    Polz-Gruszka, Dorota; Morshed, Kamal; Jarzyński, Adrian; Polz-Dacewicz, Małgorzata

    2015-01-01

    The aim of this study was to analyze the prevalence of BK virus, Human Papillomavirus and Epstein-Barr virus in oropharyngeal cancer, and to test our hypothesis that BKV/HPV/EBV co-infection plays a role in oropharyngeal squamous cell carcinoma. The correlation between viral infection, OSCC, anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated. The examination samples were collected from 62 patients from paraffin tissue blocks. Males (90.3%) with, smoking (83.9%) and alcohol abuse (67.7%) problems prevailed in the studied group. G2 histological type was recognized in 80.6% cases. T4 (77.4%) and N2 (56.5%) traits occurred in the majority of patients. No cases of metastasis were observed (M0 100%). HPV - 24.2%, EBV - 27.4% and BKV 17.7% were detected in the studied samples. We observed co-infection EBV/BKV in 8% of cases, HPV/BKV in 4.8%, and HPV/EBV in 9% cases. Only in two cases co-infection of all three viruses was found.

  14. Higher incidence of Epstein-Barr virus-induced lymphocyte transformation in multiple sclerosis

    DEFF Research Database (Denmark)

    Tørring, Caroline Winther; Andreasen, Charlotte; Gehr, Nikolaj

    2014-01-01

    Objectives Epstein–Barr virus (EBV) infection is associated with multiple sclerosis (MS), and EBV may transform lymphoblastoid cell lines more frequently in MS patients than controls, but it is not clear whether this reflects a higher viral load or an enhanced ability to reactivate EBV. Material...

  15. Roles and regulation of Epstein-Barr virus microRNAs

    NARCIS (Netherlands)

    Hooykaas, M.J.G.

    2016-01-01

    MicroRNAs are posttranscriptional gene regulators that play important roles in many cellular processes. These short non-coding RNA molecules regulate gene expression by binding to complementary target mRNAs, thereby inducing RNA destabilization and inhibition of translation. Several DNA viruses

  16. [Description of a particular case of the so-called Schmincke lymphoepithelioma and study of the correlation with Epstein-Barr virus].

    Science.gov (United States)

    Torre, V; Cavallari, V; Bucolo, S; Abbate, G; Romano, G; Fera, G; Galletti, B

    2000-10-01

    For poorly differentiated rhinopharyngeal carcinomas, the clinical presentation (association with the Epstein-Barr virus, paraneoplastic syndromes, onset of lymphoma) and the histopathological features can be polymorphous and they can confound or delay diagnosis and preparation of an adequate treatment plan (radio-chemotherapy). Often these neoplasms arise as clinically primitive laterocervical metastases, masked by clinical findings and a history that can lead to the mistaken diagnosis of systemic lymphoproliferative processes such as Hodgkin's disease. Here an observation of this type is presented in a young patient (19 years old) who came under observation for a laterocervical tumefaction recurrent from a previous exeresis performed at another hospital and symptoms of serotine febricula, dysphagia and serology positive for the Epstein-Barr virus (EBV). The patient underwent surgery and then radiotherapy and has been under close post-operative follow-up for two years. To date the patient's condition--both local and general--is good. The particular histology of the neoformation lies in the abundant infiltration of plasma cell and lymphocyte eosinophils, at times in blastic form. Moreover, elements with a large clear nucleus and evident nucleolus (Hodgkin-like) and scattered multinucleate Langhans-type giant cells can be seen. Immunohistologically the tumor cells markedly express for cytokeratin and the latent membrane protein (LMP1) of the Epstein-Barr virus (EBV) and show a high growth fraction. Under the electron microscope, the plurinucleate giant cells present large nuclei with morphology similar to that of tumor cells. The clear cytokeratin-positivity of the tumor elements and the histological and ultrastructural features mentioned led to the diagnosis of a massive metastasis from lymphoepithelial carcinoma, the Schmincke variant, plus EBV infection of the neoplastic cells. The authors conclude assuming that the particular granulomatous reaction is due to the

  17. Analysis of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) gene and promoter in Hodgkin's disease isolates

    DEFF Research Database (Denmark)

    Sandvej, K; Andresen, B S; Zhou, X G

    2000-01-01

    AIMS: To study the distribution of Epstein-Barr virus (EBV) variants containing mutations in the latent membrane protein 1 (LMP-1) oncogene and promoter in EBV associated Hodgkin's disease and infectious mononucleosis compared with previous findings in asymptomatic EBV carriers. METHODS: Sequence...... analysis of the EBV LMP-1 promoter and gene in isolates from Danish patients with Hodgkin's disease (n = 61) and infectious mononucleosis (n = 10). RESULTS: Viruses (previously designated group D) that contain two mutations in the activating transcription factor/cAMP response element (ATF/CRE) in the LMP-1...... promoter, which are known to decrease promoter activity greatly, were significantly less frequent in Hodgkin's disease than in both infectious mononucleosis (p = 0.0081) and asymptomatic EBV carriers (p = 0.0084). In some cases, the LMP-1 gene contained mutations in a recently identified cytotoxic T cell...

  18. Epstein-Barr virus infection of infants: implications of early age of infection on viral control and risk for Burkitt lymphoma

    Directory of Open Access Journals (Sweden)

    Rosemary Rochford

    2016-01-01

    Full Text Available Since its first description by Denis Burkitt, endemic Burkitt's lymphoma (BL, the most common childhood cancer in sub-Saharan Africa, has led scientists to search for clues to the origins of this malignancy. The discovery of Epstein-Barr virus (EBV in BL cells over 50 years ago led to extensive sero-epidemiology studies and revealed that rather than being a virus restricted to areas where BL is endemic, EBV is ubiquitous in the world's population with an estimated greater than 90% of adults worldwide infected. A second pathogen, Plasmodium falciparum (P. falciparum malaria is also linked to BL. In this review, we will discuss recent studies that indicate a role for P. falciparum malaria in dysregulating EBV infection, and increasing the risk for BL in children living where P. falciparum malaria transmission is high.

  19. Epstein-Barr virus infection of infants: implications of early age of infection on viral control and risk for Burkitt lymphoma.

    Science.gov (United States)

    Rochford, Rosemary

    Since its first description by Denis Burkitt, endemic Burkitt's lymphoma (BL), the most common childhood cancer in sub-Saharan Africa, has led scientists to search for clues to the origins of this malignancy. The discovery of Epstein-Barr virus (EBV) in BL cells over 50 years ago led to extensive sero-epidemiology studies and revealed that rather than being a virus restricted to areas where BL is endemic, EBV is ubiquitous in the world's population with an estimated greater than 90% of adults worldwide infected. A second pathogen, Plasmodium falciparum (P. falciparum) malaria is also linked to BL. In this review, we will discuss recent studies that indicate a role for P. falciparum malaria in dysregulating EBV infection, and increasing the risk for BL in children living where P. falciparum malaria transmission is high. Copyright © 2016. Publicado por Masson Doyma México S.A.

  20. Diagnosis of Epstein-Barr virus infection in clinical serum samples by an SPR biosensor assay

    Czech Academy of Sciences Publication Activity Database

    Riedel, Tomáš; Rodriguez-Emmenegger, Cesar; de los Santos Pereira, Andres; Bědajánková, A.; Jinoch, P.; Boltovets, P. M.; Brynda, Eduard

    2014-01-01

    Roč. 55, 15 May (2014), s. 278-284 ISSN 0956-5663 R&D Projects: GA ČR GBP205/12/G118; GA MŠk EE2.3.30.0029; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : surface plasmon resonance biosensor * real time diagnostics * Epstein–Barr virus infection Subject RIV: CE - Biochemistry Impact factor: 6.409, year: 2014

  1. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

    Science.gov (United States)

    Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

    2017-07-04

    EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

  2. Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Schultze, Detlev; Mani, Bernhard; Dollenmaier, Günter; Sahli, Roland; Zbinden, Andrea; Krayenbühl, Pierre Alexandre

    2015-10-29

    Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

  3. Coinfection with Epstein-Barr Virus (EBV), Human Papilloma Virus (HPV) and Polyoma BK Virus (BKPyV) in Laryngeal, Oropharyngeal and Oral Cavity Cancer.

    Science.gov (United States)

    Drop, Bartłomiej; Strycharz-Dudziak, Małgorzata; Kliszczewska, Ewa; Polz-Dacewicz, Małgorzata

    2017-12-19

    Most research providing evidence for the role of oncogenic viruses in head and neck squamous cell carcinoma (SCC) development is focused on one type of virus without analyzing possible interactions between two or more types of viruses. The aim of this study was to analyse the prevalence of co-infection with human papillomavirus (HPV), Epstein-Barr virus (EBV) and polyoma BK virus (BKPyV) in oral, oropharyngeal and laryngeal squamous cell carcinomas in Polish patients. The correlations between viral infection, SCC, demographic parameters, evidence of metastases and grading were also investigated. Fresh-frozen tumour tissue samples were collected from 146 patients with laryngeal, oropharyngeal and oral cancer. After DNA extraction, the DNA of the studied viruses was detected using polymerase chain rection (PCR) assay. Males (87.7%) with a history of smoking (70.6%) and alcohol abuse (59.6%) prevailed in the studied group. Histological type G2 was recognized in 64.4% cases. The patients were most frequently diagnosed with T2 stage (36.3%) and with N1 stage (45.8%). Infection with at least two viruses was detected in 56.2% of patients. In this group, co-infection with HPV/EBV was identified in 34.1% of cases, EBV/BKV in 23.2%, HPV/BKV in 22.0%, and HPV/EBV/BKV in 20.7%. No difference of multiple infection in different locations of cancer was observed. The prevalence of poorly differentiated tumours (G3) was more frequent in co-infection with all three viruses than EBV or BKV alone. A significant correlation was observed between tumour dimensions (T) and lymph-node involvement (N) in co-infected patients compared to single infection. Further studies are necessary to clarify whether co-infection plays an important role in the initiation and/or progression of oncogenic transformation of oral, oropharyngeal and laryngeal epithelial cells.

  4. A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Mehar Chand Sharma

    2016-01-01

    Results: During a period of 10 years, 65 PCNSL were diagnosed which comprised 0.69 per cent (65/9476 of all intracranial tumours. The mean age of presentation was 49 yr with sex ratio (M:F of 1.4:1. Most common location was supratentorial region with predominant involvement of frontal lobe. Single lesions were seen in 38 (58.4% and multifocal lesions in 27 (41.5% patients. None of the patients were immunocompromised. All cases were B cell immunophenotype and were DLBCL except one case of follicular lymphoma. According to Hans classification, majority of them were NGC (n=51, 79.6% and 13 (20.3% were GC type. Bcl-2 expression was noted in 34 (52.3% tumours. EBV was positive in three (4.6% cases; two were detected both by IHC and CISH and one case by CISH only. Interpretation & conclusions: In Indian population, PCNSL occurs mainly in immunocompetent patients, and a decade earlier than in western population. Immunophenotyping revealed that all cases were DLBCL with predominance of NGC type. No prognostic difference was seen between GC and NGC DLBCL. Association of EBV was rare and this virus was possibly not involved in the pathogenesis of PCNSL in immunocompetent individuals. CISH was an easy, economical and less cumbersome method for detection of EBV in PCNSL.

  5. Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin.

    Science.gov (United States)

    Wu, Chung-Chun; Fang, Chih-Yeu; Cheng, Yu-Jhen; Hsu, Hui-Yu; Chou, Sheng-Ping; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chen, Jen-Yang

    2017-01-05

    Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation. We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity. Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle. Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.

  6. [AIDS-related primary CNS non-Hodgkin's lymphoma in a patient with previous Epstein-Barr virus panuveitis. A clinico-pathological report].

    Science.gov (United States)

    Ruiz-Bilbao, S; Hernández, À; Gómez-Sánchez, S; Romeu, J; Llobera L, L; Carrato, C; Anglada, R; Sabala, A; Matas, L

    2015-05-01

    Patient with AIDS and Epstein-Barr virus (EBV) uveitis. The PCR of the aqueous and vitreous humor was positive for EBV, and DNA quantification was 56.602×10(6) copies/ml in the vitreous humor, 173,400 copies/ml in the peripheral blood, and negative in the cerebrospinal fluid (CSF). The patient developed a non-Hodgkin's lymphoma (NHL), diagnosed in the autopsy. The EBV is a rare cause of uveitis and it may be necessary to perform a quantitative PCR to reach the diagnosis. High amounts of EBV DNA are associated with a greater incidence of NHL. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome.

    Science.gov (United States)

    Ferraro, Diana; Galli, Veronica; Simone, Anna Maria; Bedin, Roberta; Vitetta, Francesca; Merelli, Elisa; Nichelli, Paolo Frigio; Sola, Patrizia

    2017-04-01

    Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years.

  8. B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus

    DEFF Research Database (Denmark)

    Munch, M; Møller-Larsen, A; Christensen, T

    1995-01-01

    On several occasions we have observed retrovirus-like particles (RVLPs) by transmission electron microscopy (EM) of cultured T cells from a patient with MS. Later we established spontaneously formed B-lymphoblastoid cell lines (LCLs) from a patient with an MS-like disease and from another patient...... with MS who had a reactivated Epstein-Barr virus (EBV) infection. Both LCLs were found by EM to produce RVLP and EBV particles. Reverse transcriptase (RT) assays were positive in purified viral material from both LCLs. To substantiate these findings we initiated an intensified culturing procedure and were...... able to establish LCLs from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls. All LCLs were found to produce both RVLP and EBV particles by EM. Whether the putative new retrovirus(es) and EBV have any causal relationship to MS is still not known, but the findings support...

  9. Surgical Treatment for Epstein-Barr Virus Otomastoiditis Complicated by Facial Nerve Paralysis: A Case Report of Two Young Brothers and Review of Literature.

    Science.gov (United States)

    Eeten, Evelien van; Faber, Hubert; Kunst, Dirk

    2017-04-01

    We report the case of two young brothers with Epstein-Barr virus (EBV) otomastoiditis complicated by a facial nerve paralysis. The boys, aged 7 months (patient A) and 2 years and 8 months (patient B), were diagnosed with a facial nerve paralysis House-Brackmann (HB) grade IV (A) and V (B). After unsuccessful pharmacological treatment, patient A underwent mastoidectomy and atticoantrotomy and patient B underwent a transmastoidal surgical decompression of the facial nerve. They recovered to HB grades I and II facial nerve palsy (FNP), respectively. Although rare and relatively unknown, EBV should be considered in the differential diagnosis of children with FNP of unknown cause. Surgical intervention may be a viable therapy with good recovery.

  10. Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Trier, Nicole; Gonzalez-Izarzugaza, Jose Maria; Chailyan, Anna

    2018-01-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors...... influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred...... to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA...

  11. Consideration of Epstein-Barr Virus-Encoded Noncoding RNAs EBER1 and EBER2 as a Functional Backup of Viral Oncoprotein Latent Membrane Protein 1

    Directory of Open Access Journals (Sweden)

    Kristina M. Herbert

    2016-03-01

    Full Text Available The Epstein-Barr virus (EBV-encoded noncoding RNAs EBER1 and EBER2 are highly abundant through all four latency stages of EBV infection (III-II-I-0 and have been associated with an oncogenic phenotype when expressed in cell lines cultured in vitro. In vivo, EBV-infected B cells derived from freshly isolated lymphocytes show that EBER1/2 deletion does not impair viral latency. Based on published quantitative proteomics data from BJAB cells expressing EBER1 and EBER2, we propose that the EBERs, through their activation of AKT in a B-cell-specific manner, are a functionally redundant backup of latent membrane protein 1 (LMP1—an essential oncoprotein in EBV-associated malignancies, with a main role in AKT activation. Our proposed model may explain the lack of effect on viral latency establishment in EBER-minus EBV infection.

  12. Phenotypic expression of mitochondrial genotypes in cultured skin fibroblasts and in Epstein-Barr virus-transformed lymphocytes in Pearson syndrome.

    Science.gov (United States)

    Rötig, A; Bourgeron, T; Rustin, P; Munnich, A

    1995-01-01

    Pearson syndrome is a fatal disorder involving the hematopoietic system and exocrine pancreas. Mitochondrial respiratory chain deficiencies and/or rearrangements of the mitochondrial DNA were consistently observed in all patients. We report here on the variant phenotypic expression of mitochondrial genotypes in cultured cells from a patient with Pearson syndrome. Skin fibroblasts and lymphocytes harbored, respectively, 60% and 80% of deleted mtDNA molecules initially and displayed defective respiratory chain activities. In both cases, there was a progressive recovery of respiratory chain activities during in vitro cell proliferation due to the loss of deleted mtDNA molecules in cultured skin fibroblasts and to an increase in the mtRNA translation efficiency in Epstein-Barr virus-transformed lymphocytes. The present study suggests that various cellular responses to abnormal mitochondrial genotypes might contribute to the tissue-specific expression of mitochondrial disorders in vivo.

  13. Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

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    Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

    2010-03-08

    Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

  14. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein-Barr virus open reading frame BCRFI

    International Nuclear Information System (INIS)

    Vieira, P.; De Waal-Malefyt, R.; Dang, M.N.; Johnson, K.E.; Kastelein, R.; Fiorentino, D.F.; DeVries, J.E.; Roncarolo, M.G.; Mosmann, T.R.; Moore, K.W.

    1991-01-01

    The authors demonstrated the existence of human cytokine synthesis inhibitory factor (DSIF) [interleukin 10 (IL-10)]. cDNA clones encoding human IL-10 (hIL-10) were isolated from a tetanus toxin-specific human T-cell clone. Like mouse IL-10, hIL-10 exhibits strong DNA and amino acid sequence homology to an open reading frame in the Epstein-Barr virus, BDRFL. hIL-10 and the BCRFI product inhibit cytokine synthesis by activated human peripheral blood mononuclear cells and by a mouse Th1 clone. Both hIL-10 and mouse IL-10 sustain the viability of a mouse mast cell line in culture, but BCRFI lacks comparable activity in this way, suggesting that BCRFI may have conserved only a subset of hIL-10 activities

  15. Association of interferon lambda-1 with herpes simplex viruses-1 and -2, Epstein-Barr virus, and human cytomegalovirus in chronic periodontitis.

    Science.gov (United States)

    Muzammil; Jayanthi, D; Faizuddin, Mohamed; Noor Ahamadi, H M

    2017-05-01

    Periodontal tissues facilitate the homing of herpes viruses that elicit the immune-inflammatory response releasing the interferons (IFN). IFN lambda-1 (λ1) can suppress the replication of viruses, and induces the antiviral mechanism. The aim of the present study was to evaluate the association between IFN-λ1 and periodontal herpes viruses in the immunoregulation of chronic periodontal disease. The cross-sectional study design included 30 chronic periodontitis patients with a mean age of 42.30 ± 8.63 years. Gingival crevicular fluid collected was assessed for IFN-λ1 using enzyme-linked immunosorbent assay and four herpes viruses were detected using multiplex polymerase chain reaction technique. IFN-λ1 levels were compared between virus-positive and -negative patients for individual and total viruses. Fifty per cent (n = 15) of patients were positive for the four herpes viruses together; 50% (n = 15), 30% (n = 9), 26.7% (n = 8), and 40% (n = 12) were positive for herpes simplex virus (HSV)-1, Epstein-Barr virus, HSV-2, and human cytomegalovirus, respectively. The mean concentrations of IFN-λ1 in virus-positive patients (14.38 ± 13.95) were lower than those of virus-negative patients (228.26 ± 215.35). INF-λ1 levels in individual virus groups were also lower in virus-positive patients compared to virus-negative patients, with P viruses in the pathogenesis of chronic periodontitis. © 2015 Wiley Publishing Asia Pty Ltd.

  16. Autoantibodies from patients with systemic lupus erythematosus bind a shared sequence of SmD and Epstein-Barr virus-encoded nuclear antigen EBNA I.

    Science.gov (United States)

    Sabbatini, A; Bombardieri, S; Migliorini, P

    1993-05-01

    SmD is one of the small nuclear ribonucleoproteins frequently targeted by autoantibodies in systemic lupus erythematosus. We isolated and characterized the antibodies present in lupus sera that are specific for the C-terminal region of SmD (sequence 95-119). This region is highly homologous to sequence 35-58 of the EBNA I antigen, one of the nuclear antigens induced by infection with Epstein-Barr virus. Antibodies affinity purified over a peptide 95-119 column were able to recognize this sequence in the context of the whole SmD molecule, as they reacted with blotted recombinant SmD. Anti-SmD 95-119 antibodies bound also the EBNA I 35-58 peptide and detected the EBNA I molecule in a total cell extract from Epstein-Barr virus-infected lines. A population of anti-SmD antibodies is, therefore, able to bind an epitope shared by the autoantigen and the viral antigen EBNA I. To investigate the involvement of this shared epitope in the generation of anti-SmD antibodies, we immunized mice with the EBNA I 35-58 peptide. Sera from immunized animals displayed the same pattern of reactivity of spontaneously produced anti-SmD antibodies. They reacted in fact with the EBNA peptide as well as with SmD 95-119 and recombinant SmD. These data suggest that molecular mimicry may play a role in the induction of anti-SmD autoantibodies.

  17. Epstein-Barr virus associated acute hepatitis with cross-reacting antibodies to other herpes viruses in immunocompetent patients: report of two cases.

    Science.gov (United States)

    Gupta, Ekta; Bhatia, Vikram; Choudhary, Aashish; Rastogi, Archana; Gupta, Naveen L

    2013-03-01

    Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM) which is characterized by the triad of fever, sore throat, and lymphadenopathy. Self-limited, mild liver function test abnormalities are seen in IM. Acute hepatitis in primary EBV infection is uncommon. Serum transaminases are elevated but are less than fivefold the normal levels in most cases and rarely exceed 10 times the normal levels in primary EBV infections especially in elderly. Laboratory diagnosis of acute EBV infection is by serological assays confirming the presence of EBV viral capsid antigen (VCA) IgM antibodies. Due to antigenic cross-reactivity with Herpes viruses, serological assays lack specificity; hence specific molecular diagnostic methods are required for confirmation of the etiology. The present report describes two cases of acute hepatitis caused by infection with EBV which had indistinguishable clinical features and biochemical markers from acute hepatitis caused by hepatotropic viruses such as hepatitis viruses A-E. The diagnosis of infection by EBV was confirmed by detection of EBV DNA in blood of both the patients and EBV DNA in the liver tissue of one of the patients. Copyright © 2013 Wiley Periodicals, Inc.

  18. Detection of cytomegalovirus, Epstein-Barr virus, and Torque Teno virus in subgingival and atheromatous plaques of cardiac patients with chronic periodontitis.

    Science.gov (United States)

    Priyanka, Sriraman; Kaarthikeyan, Gurumoorthy; Nadathur, Jayakumar Doraiswamy; Mohanraj, Anbarasu; Kavarthapu, Avinash

    2017-01-01

    Periodontitis and atherosclerosis represent a chronic inflammatory process. The incidence of periodontitis in cardiac patients with atherosclerosis is a well-established fact. The role of viruses in the etiopathogenesis of both has been proposed. The aim of the study was to evaluate the prevalence of Torque Teno virus (TTV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in cardiac patients with atherosclerosis and coexisting chronic periodontitis (CP). Thirty patients (17 males and 13 females) with atherosclerotic plaques and coexisting periodontitis were recruited for this cross-sectional study. Viral DNA was extracted from the subgingival and atheromatous plaque. The presence of CMV, EBV, and TTV in the plaque samples was identified using polymerase chain reaction. The collected data were statistically analyzed for the prevalence of the viruses and Chi-squared test was performed to find out its association with atheroma and CP. The prevalence of CMV, EBV, and TTV in atheromatous plaque was 63.3%, 56.7%, and 46.7%, respectively, as compared to rates of 80%, 63.3%, and 53.3% in subgingival plaque. Results also indicated no significant association of CMV, EBV, and TTV in both samples ( P = 0.08, 0.346, and 0.261, respectively). There was no significant association of CMV, EBV, and TTV between subgingival and atheromatous plaque. The prevalence of CMV, EBV, and TTV was high in atheromatous plaque. TTV was isolated from more than 50% of participants in atheromatous plaque, which is a significant finding.

  19. Coinfection of Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human papillomavirus and anal intraepithelial neoplasia in HIV patients in Amazon, Brazil

    Directory of Open Access Journals (Sweden)

    Adriana Gonçalves Daumas Pinheiro Guimarães

    2012-03-01

    Full Text Available OBJECTIVE: The prevention of anal cancer is a goal of worldwide Aids support centers. Despite the efforts that have been made and progress in the antiretroviral therapy, effective disease control remains elusive. Difficulty in preventing anal cancer may result from the ineffectiveness of highly active antiretroviral therapy on the human papillomavirus (HPV since the coinfection with HIV and HPV appears to increase the risk of HPV-infected cells, becoming cancerous. METHODS: We evaluated 69 HIV-positive and 30 HIV-negative male patients who underwent cytological evaluation by RT-PCR for the presence of HPV, Epstein-Barr virus, cytomegalovirus and herpes virus types (HSV 1 and 2, and histopathology analysis of the anal canal. RESULTS: The prevalence of anal intraepithelial neoplasia was 35% and it was restricted to HIV-positive patients. Patients infected with high-risk HPV and with fewer than 50 TCD4 cells/µL showed an anal intraepithelial neoplasia rate of 85.7% compared to those with TCD4 cells >200 cells/µL (pOBJETIVO: A prevenção do câncer anal tem sido aplicada pelos centros de apoio a pacientes com Aids em todo o mundo. Apesar dos esforços empregados, o eficaz controle da doença permanece distante. A dificuldade na prevenção do câncer anal pode resultar, em parte, da ineficácia da ação da terapia antirretroviral sobre o papilomavírus humano (HPV, pois a coinfecção com HIV e HPV parece aumentar o risco das células infectadas pelo HPV em tornarem-se cancerosas. MÉTODOS: Foram avaliados 69 HIV-positivos e 30 pacientes HIV-negativos do sexo masculino, que foram submetidos à avaliação citológica anal por real time-PCR para a presença de HPV, vírus Epstein-Barr, citomegalovírus e herpes vírus tipos (HSV 1 e 2 além da análise histopatológica de fragmento de mucosa do canal anal. RESULTADOS: A prevalência de neoplasia intraepitelial anal foi de 35% e foi restrita a pacientes HIV-positivos. Os pacientes infectados com o

  20. Host cell reactivation of uv- and X-ray-damaged herpes simplex virus by Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Henderson, E.E.; Long, W.K.

    1981-01-01

    The efficacy of using an infected centers assay, employing herpes simplex virus-infected, Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) as components, to study host cell reactivation has been explored. Herpes simplex virus type 1 (HSV-1) was shown through the infected centers assay to have detectable but varying ability to lytically infect LCLs established from chromosomal breakage syndromes or closely related genetic disorders. The rate of HSV inactivation by ultraviolet (uv) irradiation was faster in LCLs established from Cockaynes's syndrome than in normal LCLs, and faster still in LCLs established from xeroderma pigmentosum. These results indicate that Cockayne's syndrome, while having what appears to be quantitatively normal levels of uv-induced DNA repair replication, shows decreased ability to host cell reactivated uv-damaged HSV. In direct contrast, X-irradiated HSV showed identical survival when assayed on normal LCLs or LCLs established from ataxia telangiectasia showing increased sensitivity to X irradiation as measured by colony formation. Through the infected centers assay, it has also been possible to demonstrate low levels of multiplicity reactivation of mutagen-damaged HSV in permanently proliferating LCLs

  1. Presence of human papillomavirus-18 and Epstein-Barr virus in a squamous cell carcinoma of the tongue in a 20-year-old patient. Case report and review of the current literature

    International Nuclear Information System (INIS)

    Hermann, R.M.; Pradier, O.; Christiansen, H.; Schmidberger, H.; Fuzesi, L.

    2004-01-01

    We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr virus.To our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. We review the present data and theories concerning viral onco-genesis of oral carcinomas. (author)

  2. Presence of human papillomavirus-18 and Epstein-Barr virus in a squamous cell carcinoma of the tongue in a 20-year-old patient. Case report and review of the current literature; Presence dans un cancer epidermoide de la langue d'un papillomavirus HPV-18 et d'un virus d'Epstein-Barr chez une patiente de 20 ans. Case-report et revue de la litterature

    Energy Technology Data Exchange (ETDEWEB)

    Hermann, R.M.; Pradier, O.; Christiansen, H.; Schmidberger, H. [Georg-August Gottingen Universitat, Dept. of Radiotherapy (Germany); Fuzesi, L. [Georg-August Gottingen Universitat, Dept. of Pathology (Germany)

    2004-08-01

    We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr virus.To our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. We review the present data and theories concerning viral onco-genesis of oral carcinomas. (author)

  3. Caractérisation de la propriété de la protéine ZEBRA du virus Epstein-Barr à pénétrer dans les cellules

    OpenAIRE

    Rothe, Romy

    2010-01-01

    The basic-leucine zipper (bZIP) transcriptional activator ZEBRA of the Epstein - Barr virus was recently shown to cross the outer membrane of live cells and to accumulate in the nucleus of lymphocytes. During this PhD study, I investigated the potential application of ZEBRA as a transporter protein to facilitate transduction of cargo proteins. The analysis of different truncated forms of ZEBRA revealed that the minimal domain (MD) required for internalization was spanning residues 178-220. Th...

  4. The Epstein-Barr virus BamHI C promoter is not essential for B cell immortalization in vitro, but it greatly enhances B cell growth transformation.

    Science.gov (United States)

    Tierney, Rosemary J; Nagra, Jasdeep; Rowe, Martin; Bell, Andrew I; Rickinson, Alan B

    2015-03-01

    Epstein-Barr virus (EBV) infection of B cells leads to the sequential activation of two viral promoters, Wp and Cp, resulting in the expression of six EBV nuclear antigens (EBNAs) and the viral Bcl2 homologue BHRF1. The viral transactivator EBNA2 is required for this switch from Wp to Cp usage during the initial stages of infection. EBNA2-dependent Cp transcription is mediated by the EBNA2 response element (E2RE), a region that contains at least two binding sites for cellular factors; one of these sites, CBF1, interacts with RBP-JK, which then recruits EBNA2 to the transcription initiation complex. Here we demonstrate that the B cell-specific transcription factor BSAP/Pax5 binds to a second site, CBF2, in the E2RE. Deletion of the E2RE in the context of a recombinant virus greatly diminished levels of Cp-initiated transcripts during the initial stages of infection but did not affect the levels of Wp-initiated transcripts or EBNA mRNAs. Consistent with this finding, viruses deleted for the E2RE were not markedly impaired in their ability to induce B cell transformation in vitro. In contrast, a larger deletion of the entire Cp region did reduce EBNA mRNA levels early after infection and subsequently almost completely ablated lymphoblastoid cell line (LCL) outgrowth. Notably, however, rare LCLs could be established following infection with Cp-deleted viruses, and these were indistinguishable from wild-type-derived LCLs in terms of steady-state EBV gene transcription. These data indicate that, unlike Wp, Cp is dispensable for the virus' growth-transforming activity. Epstein-Barr virus (EBV), a B lymphotropic herpesvirus etiologically linked to several B cell malignancies, efficiently induces B cell proliferation leading to the outgrowth of lymphoblastoid cell lines (LCLs). The initial stages of this growth-transforming infection are characterized by the sequential activation of two viral promoters, Wp and Cp, both of which appear to be preferentially active in target B

  5. The Translesion Polymerase Pol η Is Required for Efficient Epstein-Barr Virus Infectivity and Is Regulated by the Viral Deubiquitinating Enzyme BPLF1.

    Science.gov (United States)

    Dyson, Ossie F; Pagano, Joseph S; Whitehurst, Christopher B

    2017-10-01

    Epstein-Barr virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. We previously showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis (TLS) pathway, a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument, indicating that BPLF1 may function both early and late during infection. The BPLF1 protein expresses deubiquitinating activity that is strictly conserved across the Herpesviridae ; mutation of the active site cysteine results in a loss of enzymatic activity. Infection with an EBV BPLF1 knockout virus results in decreased EBV infectivity. Polymerase eta (Pol η), a specialized DNA repair polymerase, functions in TLS and allows for DNA replication complexes to bypass lesions in DNA. Here we report that BPLF1 interacts with Pol η and that Pol η protein levels are increased in the presence of functional BPLF1. BPLF1 promotes a nuclear relocalization of Pol η molecules which are focus-like in appearance, consistent with the localization observed when Pol η is recruited to sites of DNA damage. Knockdown of Pol η resulted in decreased production of infectious virus, and further, Pol η was found to bind to EBV DNA, suggesting that it may allow for bypass of damaged viral DNA during its replication. The results suggest a mechanism by which EBV recruits cellular repair factors, such as Pol η, to sites of viral DNA damage via BPLF1, thereby allowing for efficient viral DNA replication. IMPORTANCE Epstein-Barr virus is the causative agent of infectious mononucleosis and infects approximately 90% of the world's population. It causes lymphomas in individuals with acquired and innate immune disorders and is strongly associated with Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphomas, nasopharyngeal carcinoma (NPC), and

  6. UV-inactivation of Epstein-Barr virus: differences in early antigen expression in two different non-productive cell lines and influence of caffeine

    International Nuclear Information System (INIS)

    Suchankova, A.; Vonka, V.

    1978-01-01

    Two non-productive Epstein-Barr (EB) virus genome-carrying lymphoblastoid cell lines, namely Raji and NC37, were used for studying the effect of UV irradiation on the ability of P3HR-1 EB virus to induce early antigen (EA) formation. In NC37 cells infected with UV-irradiated virus the formation of EA was delayed; thus the slope of inactivation curve based on the early (24 hr) reading was steeper than that based on the late (72 hr) reading. This was not observed in Raji cells. Caffeine did not influence the percentage of EA positive cells in cultures infected with untreated virus; however, the drug exhibited a marked inhibitory effect on EA production after infection with UV-irradiated virus. The sensitivity to caffeine decreased more rapidly with time after infection of Raji than of NC37 cells, suggesting a higher degree of readiness of the host cell repair system in the former than in the latter cells. The caffeine effect was merely directed against the synthesis of R (restricted) component of EA; its influence on the D (diffuse) component formation was negligible. (author)

  7. Evaluation Frequency of Merkel Cell Polyoma, Epstein-Barr and Mouse Mammary Tumor Viruses in Patients with Breast Cancer in Kerman, Southeast of Iran.

    Science.gov (United States)

    Reza, Malekpour Afshar; Reza, Mollaie Hamid; Mahdiyeh, Lashkarizadeh; Mehdi, Fazlalipour; Hamid, Zeinali Nejad

    2015-01-01

    Breast cancer is the most common cancer among women worldwide. Roles of the Epstein-Barr, Merkel cell polyoma and mouse mammary tumor viruses in breast carcinogenesis are still controversial although any relationship would clearly be important for breast cancer etiology, early detection and prevention. In the present study associations between EBV, MMTV and Merkel cell polyoma virus and breast cancer in 100 Iranian patients were evaluated using paraffin-embedded tissues. EBER RNA and expression of p53 and large T antigen were evaluated by real time PCR and CD34, p63, HER2, PR and ER markers were studied by immunohistochemistry. EBV was detected in 8/100 (8%), MMTV in 12/100 (12%), MPy in 3/100 (3%) and EBER RNA in 18/100 (18%) cases. None of the control samples demonstrated any of the viruses. p53 was suppressed in EBV, MPy and MMTV positive samples. The large T antigen rate was raised in MPy positive samples. Our results showed that EBV, MMTV and the Merkel cell polyoma virus are foundwith some proportion of breast cancers in our patients, suggesting that these viruses might have a significant role in breast cancer in Kerman, southeast of Iran.

  8. Coprevalence of Epstein-Barr Virus, Cytomegalovirus, and Herpes Simplex Virus Type-1 Antibodies Among United States Children and Factors Associated With Their Acquisition.

    Science.gov (United States)

    Delaney, Amanda S; Thomas, William; Balfour, Henry H

    2015-12-01

    Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus type-1 (HSV-1) infections are common worldwide, but age-specific prevalence of primary infection varies by race or ethnicity and geographical location. Comparing demographic groups could identify factors influencing the rate of acquisition, age-specific antibody prevalence is relevant for determining when to administer prophylactic vaccines, and coprevalence suggests similar risk factors. Stored sera collected from the cross-sectional National Health and Nutrition Examination Surveys 2003-2004 cycle were tested for EBV, CMV, and HSV-1 antibody. Demographic information was obtained through self-reported questionnaires. Statistical analysis included logistic regression and multivariate analysis adjusting for the multistage cluster design. Overall, 36% of children had antibody against 2 or more of the viruses. Coprevalence with EBV, CMV, and HSV-1 was higher in females, in non-Hispanic blacks, and Mexican Americans, compared with non-Hispanic whites, and in those without health insurance. Antibody prevalence was associated with (1) lower household income and education and (2) greater crowding. Nearly all children with CMV antibody or HSV-1 antibody had been infected with EBV. There was a disproportionately high prevalence of EBV, CMV, and HSV-1 antibody among Mexican Americans and non-Hispanic blacks, groups with a lower poverty income ratio, and those with less household education. They might benefit from receiving prophylactic herpes vaccines when fairly young. The presence of EBV, CMV, or HSV-1 antibody increases the odds of having antibody against one of the other viruses and is a ripe area for future research. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Role of ATM in the Formation of the Replication Compartment during Lytic Replication of Epstein-Barr Virus in Nasopharyngeal Epithelial Cells

    Science.gov (United States)

    Hau, Pok Man; Deng, Wen; Jia, Lin; Yang, Jie; Tsurumi, Tatsuya; Chiang, Alan Kwok Shing; Huen, Michael Shing-Yan

    2014-01-01

    ABSTRACT Epstein-Barr virus (EBV), a type of oncogenic herpesvirus, is associated with human malignancies. Previous studies have shown that lytic reactivation of EBV in latently infected cells induces an ATM-dependent DNA damage response (DDR). The involvement of ATM activation has been implicated in inducing viral lytic gene transcription to promote lytic reactivation. Its contribution to the formation of a replication compartment during lytic reactivation of EBV remains poorly defined. In this study, the role of ATM in viral DNA replication was investigated in EBV-infected nasopharyngeal epithelial cells. We observed that induction of lytic infection of EBV triggers ATM activation and localization of DDR proteins at the viral replication compartments. Suppression of ATM activity using a small interfering RNA (siRNA) approach or a specific chemical inhibitor profoundly suppressed replication of EBV DNA and production of infectious virions in EBV-infected cells induced to undergo lytic reactivation. We further showed that phosphorylation of Sp1 at the serine-101 residue is essential in promoting the accretion of EBV replication proteins at the replication compartment, which is crucial for replication of viral DNA. Knockdown of Sp1 expression by siRNA effectively suppressed the replication of viral DNA and localization of EBV replication proteins to the replication compartments. Our study supports an important role of ATM activation in lytic reactivation of EBV in epithelial cells, and phosphorylation of Sp1 is an essential process downstream of ATM activation involved in the formation of viral replication compartments. Our study revealed an essential role of the ATM-dependent DDR pathway in lytic reactivation of EBV, suggesting a potential antiviral replication strategy using specific DDR inhibitors. IMPORTANCE Epstein-Barr virus (EBV) is closely associated with human malignancies, including undifferentiated nasopharyngeal carcinoma (NPC), which has a high

  10. Epstein-Barr Virus Rta-Mediated Accumulation of DNA Methylation Interferes with CTCF Binding in both Host and Viral Genomes.

    Science.gov (United States)

    Chen, Yen-Ju; Chen, Yu-Lian; Chang, Yao; Wu, Chung-Chun; Ko, Ying-Chieh; Tsao, Sai Wah; Chen, Jen-Yang; Lin, Su-Fang

    2017-08-01

    Rta, an Epstein-Barr virus (EBV) immediate-early protein, reactivates viral lytic replication that is closely associated with tumorigenesis. In previous studies, we demonstrated that in epithelial cells Rta efficiently induced cellular senescence, which is an irreversible G 1 arrest likely to provide a favorable environment for productive replications of EBV and Kaposi's sarcoma-associated herpesvirus (KSHV). To restrict progression of the cell cycle, Rta simultaneously upregulates CDK inhibitors and downregulates MYC, CCND1, and JUN, among others. Rta has long been known as a potent transcriptional activator, thus its role in gene repression is unexpected. In silico analysis revealed that the promoter regions of MYC , CCND1 , and JUN are common in (i) the presence of CpG islands, (ii) strong chromatin immunoprecipitation (ChIP) signals of CCCTC-binding factor (CTCF), and (iii) having at least one Rta binding site. By combining ChIP assays and DNA methylation analysis, here we provide evidence showing that Rta binding accumulated CpG methylation and decreased CTCF occupancy in the regulatory regions of MYC , CCND1 , and JUN , which were associated with downregulated gene expression. Stable residence of CTCF in the viral latency and reactivation control regions is a hallmark of viral latency. Here, we observed that Rta-mediated decreased binding of CTCF in the viral genome is concurrent with virus reactivation. Via interfering with CTCF binding, in the host genome Rta can function as a transcriptional repressor for gene silencing, while in the viral genome Rta acts as an activator for lytic gene loci by removing a topological constraint established by CTCF. IMPORTANCE CTCF is a multifunctional protein that variously participates in gene expression and higher-order chromatin structure of the cellular and viral genomes. In certain loci of the genome, CTCF occupancy and DNA methylation are mutually exclusive. Here, we demonstrate that the Epstein-Barr virus (EBV

  11. Development of a time-resolved fluorescence immunoassay for Epstein-Barr virus Zta IgA antibodies in human serum.

    Science.gov (United States)

    Chen, Juanjuan; Liu, Tiancai; Chen, Zhenhua; Hou, Jingyuan; Wu, Yingsong; Li, Ming

    2015-04-01

    The Epstein-Barr virus (EBV) transactivator protein (ZEBRA) is an immediate-early protein that plays an important role in the switch from latency to productive cycle in EBV virus. ZEBRA is an important marker of EBV reactivation. In order to diagnose EBV infection status correctly and timely, a novel immunoassay was developed based on an indirect time-resolved fluoroimmunoassay (TRFIA) for Zta IgA, which used recombinant Zta antigen as solid-phase antigen and Eu(3+)-labeled mouse antihuman IgA as corresponding probe. The precision, sensitivity, specificity test, and stability of the TRFIA kit were evaluated, and comparison with the traditional enzyme-linked immunosorbent assay (ELISA) was also investigated. The cutoff value for the TRFIA was 2.5. Intra- and interassay coefficients of variation for the TRFIA were 2.45-3.30% and 3.38-4.61% respectively. There was no cross-reactivity with the antibodies of cytomegalovirus (CMV) or herpes simplex virus (HSV) types 1 and 2, or other potential interferences. The established assay kit also behaved better in sensitivity and stability than the ELISA one. Additionally, the results in 382 serum samples using two analytical methods showed there was good agreement between the TRFIA and commercial ELISA kit. In the current study, the results demonstrated that the TRFIA that was developed for Zta IgA detection was more sensitive and reliable for the diagnosis of EBV infection and had potential value in automation and high-throughput screening.

  12. Clonal deleted latent membrane protein 1 variants of Epstein-Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment.

    Science.gov (United States)

    Halabi, Mohamad Adnan; Jaccard, Arnaud; Moulinas, Rémi; Bahri, Racha; Al Mouhammad, Hazar; Mammari, Nour; Feuillard, Jean; Ranger-Rogez, Sylvie

    2016-08-15

    Extranodal natural killer/T-cell lymphomas (NK/TL), rare in Europe, are Epstein-Barr virus (EBV) associated lymphomas with poor outcomes. Here, we determined the virus type and analyzed the EBV latent membrane protein-1 (LMP1) gene sequence in NK/TL from French patients. Six clones of viral LMP1 were sequenced by Sanger technology in blood from 13 patients before treatment with an l-asparaginase based regimen and, for 8 of them, throughout the treatment. Blood LMP1 sequences from 21 patients without any known malignancy were tested as controls. EBV Type A was identified for 11/13 patients and for all controls. Before treatment, a clonal LMP1 gene containing a 30 bp deletion (del30) was found in 46.1% of NK/TL and only in 4.8% of controls. Treatment was less effective in these patients who died more rapidly than the others. Patients with a deleted strain evolving toward a wild-type strain during treatment reached complete remission. The LMP1 gene was sequenced by highly sensitive next-generation sequencing technology in five NK/TL nasopharyngeal biopsies, two of them originating from the previous patients. Del30 was present in 100% of the biopsies; two viruses at least coexisted in three biopsies. These results suggest that del30 may be associated with poor prognosis NK/TL and that strain evolution could be used as a potential marker to monitor treatment. © 2016 UICC.

  13. Drug Reaction with Eosinophilia and Systemic Symptoms Associated with Reactivation of Epstein-Barr Virus and/or Cytomegalovirus Leading to Hemophagocytic Syndrome in One of Two Patients.

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    Liang, Jianhua; Qu, Hui; Wang, Xiaowen; Wang, Aiping; Liu, Lingling; Tu, Ping; Li, Ruoyu; Wang, Mingyue

    2018-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction characterized by maculopapular rash, exfoliative dermatitis, lymphadenopathy, fever, eosinophilia, and involvement of internal organs. Evidence for reactivation of herpes family viruses has been observed in some DRESS patients, and activated CD8+ T lymphocytes are largely directed against Epstein-Barr virus. Here, we report two cases complicated with this infection. Both patients received antibiotics and non-steroidal anti-inflammatory drugs. These patients manifested clinically with high fever, facial edema, diffuse pruritic erythroderma and maculopapules over the entire body, purpuric rashes in both lower limbs and lymphadenopathy of cervical and inguinal nodes. Laboratory tests revealed abnormal liver function, blood eosinophils, and ferritin levels. The patients recovered completely; however, the female patient developed hemophagocytic syndrome on the 15th day of illness. She developed new itchy rash, and laboratory tests rapidly worsened with fibrinogen levels dramatically reduced to 0.61 g/L. Bone marrow aspiration revealed an increased number of macrophages with hemophagocytosis and a reversed CD4/CD8 ratio of 0.45. These cases suggest that human herpes virus and coagulation function evaluations are necessary in DRESS patients.

  14. Tonsillar CD56brightNKG2A+ NK cells restrict primary Epstein-Barr virus infection in B cells via IFN-γ.

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    Jud, Aurelia; Kotur, Monika; Berger, Christoph; Gysin, Claudine; Nadal, David; Lünemann, Anna

    2017-01-24

    Natural killer (NK) cells constitute the first line of defense against viruses and cancers cells. Epstein-Barr virus (EBV) was the first human virus to be directly implicated in carcinogenesis, and EBV infection is associated with a broad spectrum of B cell lymphomas. How NK cells restrict EBV-associated oncogenesis is not understood. Here, we investigated the efficacies and mechanisms of distinct NK cell subsets from tonsils, the portal of entry of EBV, in limiting EBV infection in naïve, germinal center-associated and memory B cells. We found that CD56bright and NKG2A expression sufficiently characterizes the potent anti-EBV capacity of tonsillar NK cells. We observed restriction of EBV infection in B cells as early as 18 hours after infection. The restriction was most efficient in naïve B cells and germinal center-associated B cells, the B cell subsets that exhibited highest susceptibility to EBV infection in vitro. IFN-γ release by and partially NKp44 engagement of CD56bright and NKG2A positive NK cells mediated the restriction that eventually inhibited B-cell transformation. Thus, harnessing CD56brightNKG2A+ NK cell function might be promising to improve treatment strategies that target EBV-associated B cell lymphomas.

  15. Development of a robust, higher throughput green fluorescent protein (GFP)-based Epstein-Barr Virus (EBV) micro-neutralization assay.

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    Lin, Rui; Heeke, Darren; Liu, Hui; Rao, Eileen; Marshall, Jason D; Chio, Vera; Cataniag, Floro; Yu, Li; Zuo, Fengrong; McCarthy, Michael P

    2017-09-01

    The goal of most prophylactic vaccines is to elicit robust and effective neutralizing antibodies against the human pathogen target. The titer of neutralizing antibodies to Epstein-Barr Virus (EBV) is a useful biomarker for evaluating EBV vaccines. Here, the development and optimization of a 96-well micro-neutralization fluorescent imaging assay (FIA) using an EBV virus-encoding green fluorescent protein (GFP) to infect adherent EBV recipient cells is reported. The conditions were optimized for generating reproducible EBV-GFP virus, for maintaining viral infectivity for months, and for efficient viral infection of recipient cell culture. The utility of the EBV-GFP FIA neutralization assay was demonstrated in a mouse study of an investigational adjuvanted EBV gp350 subunit vaccine. This assay confirmed the generation of high titers of anti-EBV-neutralizing antibodies which correlated well with the established Raji cell-based flow cytometry-based EBV neutralization assay, as well as with anti-gp350 IgG titers. In naturally infected EBV+ human serum samples, a good correlation between anti-gp350 IgG ELISA titer and EBV-GFP FIA neutralization antibody titer was also observed. Taken together, these results demonstrate the establishment of a scalable high throughput EBV-GFP FIA micro-neutralization assay suitable to measure humoral EBV vaccine response in a large-scale human trial. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Epstein Barr virus-encoded EBNA1 interference with MHC class I antigen presentation reveals a close correlation between mRNA translation initiation and antigen presentation.

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    Sebastien Apcher

    Full Text Available Viruses are known to employ different strategies to manipulate the major histocompatibility (MHC class I antigen presentation pathway to avoid recognition of the infected host cell by the immune system. However, viral control of antigen presentation via the processes that supply and select antigenic peptide precursors is yet relatively unknown. The Epstein-Barr virus (EBV-encoded EBNA1 is expressed in all EBV-infected cells, but the immune system fails to detect and destroy EBV-carrying host cells. This immune evasion has been attributed to the capacity of a Gly-Ala repeat (GAr within EBNA1 to inhibit MHC class I restricted antigen presentation. Here we demonstrate that suppression of mRNA translation initiation by the GAr in cis is sufficient and necessary to prevent presentation of antigenic peptides from mRNAs to which it is fused. Furthermore, we demonstrate a direct correlation between the rate of translation initiation and MHC class I antigen presentation from a certain mRNA. These results support the idea that mRNAs, and not the encoded full length proteins, are used for MHC class I restricted immune surveillance. This offers an additional view on the role of virus-mediated control of mRNA translation initiation and of the mechanisms that control MHC class I restricted antigen presentation in general.

  17. EBER2 RNA-induced transcriptome changes identify cellular processes likely targeted during Epstein Barr Virus infection

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    Benecke Bernd-Joachim

    2008-10-01

    Full Text Available Abstract Background Little is known about the physiological role of the EBER1 and 2 nuclear RNAs during Epstein Barr viral infection. The EBERs are transcribed by cellular RNA Polymerase III and their strong expression results in 106 to 107 copies per EBV infected cell, making them reliable diagnostic markers for the presence of EBV. Although the functions of most of the proteins targeted by EBER RNAs have been studied, the role of EBERs themselves still remains elusive. Findings The cellular transcription response to EBER2 expression using the wild-type and an internal deletion mutant was determined. Significant changes in gene expression patterns were observed. A functional meta-analysis of the regulated genes points to inhibition of stress and immune responses, as well as activation of cellular growth and cytoskeletal reorganization as potential targets for EBER2 RNA. Different functions can be assigned to different parts of the RNA. Conclusion These results provide new avenues to the understanding of EBER2 and EBV biology, and set the grounds for a more in depth functional analysis of EBER2 using transcriptome activity measurements.

  18. Variation in risk and outcomes of Epstein-Barr virus-associated breast cancer by epidemiologic characteristics and virus detection strategies: an exploratory study.

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    Glaser, Sally L; Canchola, Alison J; Keegan, Theresa H M; Clarke, Christina A; Longacre, Teri A; Gulley, Margaret L

    2017-04-01

    A relationship of Epstein-Barr virus (EBV) and breast cancer etiology and outcome may have clinical utility and potential to enhance understanding of tumor biology. Research to date has yielded variable results, likely reflecting differing virus detection assays and unaddressed epidemiologic heterogeneity across studies. Applying our novel, five-target assay detection strategy in an exploratory study, we examined demographic, clinical, and tumor characteristics, and overall survival, associated with EBV positivity in breast adenocarcinomas from 59 non-Hispanic white and 68 Hispanic women sampled by age (<50, 50+) and stage (localized, regional/remote) and examined associations based on single assay targets. EBV was localized only to lymphocytes. Nevertheless, viral prevalence, although low, varied across patient subgroups. Adjusted odds ratios (OR) for EBV positivity were lower for younger Hispanic than white women (p interaction  = 0.05), and marginally higher for larger [OR (95% confidence intervals) 1.03 (1.00-1.05) per mm increase] and right-sided [2.8 (0.97-7.8)] tumors. In whites, ORs were marginally higher for larger tumors [1.04 (1.00-1.07)] and marginally lower for age 50+ [0.24 (0.06-1.03)]; in Hispanics, ORs were higher for ER negative [5.6 (1.1-30.5)], and marginally higher for right-sided, tumors [5.8 (0.94-36.2)]. Survival was suggestively poorer for EBV-positive than EBV-negative tumors in older women with localized disease. EBV associations differed across single assay targets, indicating variation in prior findings likely due to assay performance. The differing EBV associations by age and race/ethnicity suggest a non-random role of EBV in breast cancer and support further study using multi-target assays, relevant epidemiologic design, and a larger study sample.

  19. Significance of Epstein-Barr virus (HHV-4 and CMV (HHV-5 infection among subtype-C human immunodeficiency virus-infected individuals

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    J Sachithanandham

    2014-01-01

    Full Text Available Purpose: Opportunistic viral infections are one of the major causes of morbidity and mortality in HIV infection and their molecular detection in the whole blood could be a useful diagnostic tool. Objective: The frequency of opportunistic DNA virus infections among HIV-1-infected individuals using multiplex real-time PCR assays was studied. Materials and Methods: The subjects were in two groups; group 1: Having CD4 counts 350 cells/µl (n = 173. Individuals were classified by WHO clinical staging system. Samples from 70 healthy individuals were tested as controls. In-house qualitative multiplex real-time PCR was standardised and whole blood samples from 291 were tested, followed by quantitative real-time PCR for positives. In a proportion of samples genotypes of Epstein-Barr virus (EBV and CMV were determined. Results: The two major viral infections observed were EBV and CMV. The univariate analysis of CMV load showed significant association with cryptococcal meningitis, oral hairy leukoplakia (OHL, CMV retinitis, CD4 counts and WHO staging (P < 0.05 while the multivariate analysis showed an association with OHL (P = 0.02 and WHO staging (P = 0.05. Univariate analysis showed an association of EBV load with CD4 counts and WHO staging (P < 0.05 and multivariate analysis had association only with CD4 counts. The CMV load was significantly associated with elevated SGPT and SGOT level (P < 0.05 while the EBV had only with SGOT. Conclusion: This study showed an association of EBV and CMV load with CD4+ T cell counts, WHO staging and elevated liver enzymes. These viral infections can accelerate HIV disease and multiplex real-time PCR can be used for the early detection. Genotype 1 and 2 of EBV and genotype gB1 and gB2 of CMV were the prevalent in the HIV-1 subtype C-infected south Indians.

  20. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation

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    Christin, Anne; Myers, Gary D.; Liu, Hao; Cruz, Conrad R.; Hanley, Patrick J.; Kennedy-Nasser, Alana A.; Leung, Kathryn S.; Gee, Adrian P.; Krance, Robert A.; Brenner, Malcolm K.; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.

    2009-01-01

    Viral infection or reactivation remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. We now show that infusions of single cytotoxic T lymphocyte (CTL) lines (5 × 106-1.35 × 108 cells/m2) with specificity for 2 commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplantation recipients receiving partially human leukocyte antigen–matched and haploidentical stem cell grafts (n = 13), without inducing graft-versus-host disease. The EBV-specific component of the CTLs expanded in vivo and persisted for more than 12 weeks, but the adenovirus-specific component only expanded in vivo in the presence of concomitant adenoviral infection. Nevertheless, adenovirus-specific T cells could be detected for at least 8 weeks in peripheral blood, even in CTL recipients without viral infection, provided the adenovirus-specific component of their circulating lymphocytes was first expanded by exposure to adenoviral antigens ex vivo. After infusion, none of these 13 high-risk recipients developed EBV-associated lymphoproliferative disease, while 2 of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenovirus-specific T cells can safely reconstitute an antigen responsive “memory” population of CTLs after human leukocyte antigen–mismatched stem cell transplantation and may provide antiviral activity. This trial was registered at www.clinicaltrials.gov as #NCT00590083. PMID:19700662

  1. Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease.

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    Ciccocioppo, Rachele; Racca, Francesca; Scudeller, Luigia; Piralla, Antonio; Formagnana, Pietro; Pozzi, Lodovica; Betti, Elena; Vanoli, Alessandro; Riboni, Roberta; Kruzliak, Peter; Baldanti, Fausto; Corazza, Gino Roberto

    2016-02-01

    The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.

  2. A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression.

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    Lin, San San; Lee, Davy C W; Law, Anna H Y; Fang, Jun Wei; Chua, Daniel T T; Lau, Allan S Y

    2010-05-01

    Expression of Epstein-Barr virus-encoded oncogenic latent membrane protein 1 (LMP1) has been substantially associated with tumorigenic transformation in the virus-infected cells. The pathogenic complexity of LMP1 is partly due to the cytokine dysregulation including IL-6 and IL-10 in perturbing the host immune responses. Here we have identified an important signaling event mediated by a dsRNA-dependent serine/threonine protein kinase, PKR, in regulating LMP1-induced IL-6 and IL-10 expression. We first demonstrated that PKR plays a significant role in mediating LMP1-induced cytokine expression by using a PKR inhibitor 2-aminopurine, and the specific role of PKR involved was confirmed by the use of siRNA oligos targeting PKR and/or a dominant-negative PKR mutant. We next revealed that PKR activity mediates LMP1-enhanced NF-kappaB nuclear translocation resulting in cytokine induction. We further demonstrated at the chromatin level that LMP1 can significantly elevate the phosphorylation of histone H3 on serine 10 (Ser 10), and the process was dependent on PKR activity. Our findings thus suggest that PKR plays an important role in mediating the cytokine gene expression induced by LMP1 through NF-kappaB activation and histone H3 Ser 10 phosphorylation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Ekspresi mRNA LMP2A Epstein-Barr Virus dari Biopsi Jaringan dalam Blok Parafin Berpotensi sebagai Biomarka dalam Diagnosis Karsinoma Nasofaring

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    Roni Afriansya

    2017-08-01

    Full Text Available Karsinoma nasofaring (KNF merupakan tumor epitel yang terletak di nasofaring dan merupakan penyakit genetik multifaktor yang endemik. Penyebab utama KNF adalah infeksi oleh Virus Epstein-Barr (EBV. Keberadaan EBV pada penderita KNF dapat diketahui dengan ditemukannya DNA EBV dalam spesimen biopsi jaringan penderita KNF. Genom EBV dan ekspresi sebagian dari produk gen laten virus secara konsisten terdeteksi hampir di setiap sel dalam kanker ini, salah satunya adalah gen Latent Membrant Protein (LMP. Aktivitas mRNA EBV lebih mencerminkan patogenesis KNF yang  sesungguhnya dari pada diagnosis serologi dan pengukuran DNA EBV di sirkulasi. Penelitian dilakukan di Laboratorium PA RSUD Margono Seokarjo, Purwokerto/Lab PA Fakultas Kedokteran dan laboratorium genetika/molekuler Universitas Jenderal Soedirman Purwokerto. Analisis Ekspresi mRNA LMP2A EBV dengan teknik one step RT-PCR dan produk RT-PCR (amplikon cDNA divisualisasi dengan elektroforesis gel agarosa 1%. Hasil ekspresi mRNA LMP2A EBV adalah 27,3% (6 dari 22 sampel. Kesimpulan, metode one step RT-PCR dapat digunakan untuk menganalisis ekspresi mRNA LMP2A EBV dari sampel biopsi jaringan KNF dalam blok paraffin dan hasil positivitas ekspresi mRNA LMP2A EBV sedang, sehingga berpotensi digunakan sebagai petanda biologi molekul diagnosis KNF.

  4. Acute renal failure in a child with thrombocytopenic purpura caused by acute Epstein-Barr virus infection after treatment with anti-D immunoglobulin.

    Science.gov (United States)

    Kossiva, Lydia; Kyriakou, Dimitrios; Mitsioni, Andromachi; Garoufi, Anastasia

    2013-06-01

    Immune thrombocytopenia (ITP) in children is usually a benign, self-limiting disorder. An acute Epstein-Barr virus (EBV) infection usually causes atypical lymphocytosis and mild decrease in platelets. Severe thrombocytopenia is an extremely rare complication. Anti-D immunoglobulin has been used for treatment of ITP in Rh(D)-positive nonsplenectomized patients. Severe hemolysis and acute renal failure are extremely rare complications that may be aggravated by the presence of an acute EBV infection. It is believed that anti-D immunoglobulin triggers an unusual virus-induced immune response causing hemolysis. We present a 4-year-old girl with ITP caused by an acute EBV infection that developed acute kidney injury following treatment with anti-D immunoglobulin. The patient recovered completely from thrombocytopenia and renal dysfunction. Intravascular hemolysis and acute kidney injury are consistent with anti-D immunoglobulin mechanism of action. Pediatric patients treated with anti-D immunoglobulin for ITP should be closely monitored for signs and symptoms of hemolysis that may be aggravated by the presence of EBV infection leading to impaired renal function.

  5. Design and evaluation of protein expression in a recombinant plasmid encoding epitope gp 350/220 of the Epstein-Barr virus (EBV)

    Science.gov (United States)

    Himmah, Karimatul; Dluha, Nurul; Anyndita, Nadya V. M.; Rifa'i, Muhaimin; Widodo

    2017-05-01

    The Epstein - Barr virus (EBV) causes severe infections that may lead to cancers such as nasopharyngeal carcinoma. Development of effective EBV vaccines is necessary to prevent the virus spreading throughout the community. TheEBV has a surface protein gp 350/220, which serves as an antigen to help interact with host cells. Epitopes of the protein can potentially serve as bases for a vaccine. In a previous study, we have found a conserved epitope of gp 350/220 from all strains EBV through an in silico approach. The aim of this study is to design and overproduce a recombinant peptide of epitope gp 350/220 in E. coli. DNA encoding the conserved epitope was synthesized and cloned into plasmid pET-22b(+); the recombinant plasmid was transformed into E. coli strains DH5α and BL21. The transformed plasmid DNA was isolated and confirmed by restriction using XbaI and PstI enzymes followed by DNA sequencing. Protein expression was induced by isopropyl-D-thiogalactopyranoside (IPTG) with final concentrations of 0.1, 0.2, 1, and 2 mM in consecutive times. An osmotic shock method was used to isolate protein from periplasmic fraction of E. coli DH5α and BL21. The SDS-PAGE analysis was carried out to detect peptide target (3.4 kDa). Based on this result, the induction process did not work properly, and thus needs further investigation.

  6. Facial nerve palsy secondary to Epstein-Barr virus infection of the middle ear in pediatric population may be more common than we think.

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    Vogelnik, Katarina; Matos, Aleš

    2017-11-01

    Facial nerve palsy is a rare complication of acute otitis media (AOM). The general understanding is that this complication has a bacterial cause although bacteria can be isolated from the middle ear only in approximately two-thirds of cases of AOM. Detection of viral agents from specimens obtained during myringotomy in patients with AOM suggests a possible role of viruses in the etiology of this disease. We studied 5 otherwise healthy 17- to 27-month-old children who were referred to the Department of Otorhinolaryngology and Cervicofacial Surgery from December 2012 to January 2016 because of AOM and ipsilateral facial nerve palsy. In all cases, serological tests were indicative of a primary Epstein-Barr virus (EBV) infection and no other causative pathogens were identified during hospitalization. In one patient, the technique of in situ hybridization (ISH) detected EBV-specific ribonucleic acid (RNA) sequences within tissue sections obtained during mastoidectomy. The aim of this article is to alert clinicians that AOM induced facial nerve palsy secondary to an acute EBV infection in the pediatric population is very likely more common than originally thought. To our knowledge until the present case series, only 2 cases of AOM induced facial nerve palsy secondary to an acute EBV infection have been reported and no cases of EBV infection proven by the ISH technique showing the presence of EBV-specific RNA sequences in patient's tissue biopsies have been reported until now.

  7. EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers.

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    Wilson, Joanna B; Manet, Evelyne; Gruffat, Henri; Busson, Pierre; Blondel, Marc; Fahraeus, Robin

    2018-04-06

    The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC) class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another means to cripple

  8. Quantitative analysis of human leucocyte antigen expression during culture of Epstein-Barr virus-transformed cell lines using the dako QIFIKIT.

    Science.gov (United States)

    Battle, R; Clark, B

    2007-01-01

    Pre-existing donor-specific human leucocyte antigen (HLA) antibodies in renal allograft recipients result in hyperacute and accelerated graft failure. These antibodies can be detected in flow cytometric assay systems using HLA-characterised Epstein-Barr virus (EBV)-transformed B-lymphocyte cell lines. Confident assay performance is predicated by the expression of HLAs on the EBV-transformed B-cell line surface. Surface HLA expression of three EBV-transformed B-cell lines that had previously been used as part of a potential organ recipient serum screening panel at St James' University Hospital, Leeds, are assessed for changes in the level of HLA expression over the nominal culture duration of eight days using the QIFIKIT (Dako, Denmark), a quantitative flow cytometry kit for assessing cell surface antigens. A comparison of the mean fluorescence intensity (MFI) of the known antigen levels of the beads via a calibration graph permits determination of the antibody binding capacity of the cell lines. Results showed that HLA expression is not consistent throughout the cell culture, with optimal expression occurring during day 2 of culture. Inconsistent HLA expression demonstrated during the cell culture means that no assumption of the level of HLA expression can be made, and that cell lines used as part of a screening panel should have their HLA expression in cell culture determined.

  9. Epstein-Barr virus from Burkitt Lymphoma biopsies from Africa and South America share novel LMP-1 promoter and gene variations.

    Science.gov (United States)

    Lei, Haiyan; Li, Tianwei; Li, Bingjie; Tsai, Shien; Biggar, Robert J; Nkrumah, Francis; Neequaye, Janet; Gutierrez, Marina; Epelman, Sidnei; Mbulaiteye, Sam M; Bhatia, Kishor; Lo, Shyh-Ching

    2015-11-23

    Epstein Barr virus (EBV) sequence variation is thought to contribute to Burkitt lymphoma (BL), but lack of data from primary BL tumors hampers efforts to test this hypothesis. We directly sequenced EBV from 12 BL biopsies from Ghana, Brazil, and Argentina, aligned the obtained reads to the wild-type (WT) EBV reference sequence, and compared them with 100 published EBV genomes from normal and diseased people from around the world. The 12 BL EBVs were Type 1. Eleven clustered close to each other and to EBV from Raji BL cell line, but away from 12 EBVs reported from other BL-derived cell lines and away from EBV from NPC and healthy people from Asia. We discovered 23 shared novel nucleotide-base changes in the latent membrane protein (LMP)-1 promoter and gene (associated with 9 novel amino acid changes in the LMP-1 protein) of the 11 BL EBVs. Alignment of this region for the 112 EBV genomes revealed four distinct patterns, tentatively termed patterns A to D. The distribution of BL EBVs was 48%, 8%, 24% and 20% for patterns A to D, respectively; the NPC EBV's were Pattern B, and EBV-WT was pattern D. Further work is needed to investigate the association between EBV LMP-1 patterns with BL.

  10. Chronic active Epstein-Barr virus infection as the initial symptom in a Janus kinase 3 deficiency child: Case report and literature review.

    Science.gov (United States)

    Zhong, Linqing; Wang, Wei; Ma, Mingsheng; Gou, Lijuan; Tang, Xiaoyan; Song, Hongmei

    2017-10-01

    With the progress of sequencing technology, an increasing number of atypical primary immunodeficiency (PID) patients have been discovered, including Janus kinase 3 (JAK3) gene deficiency. We report a patient who presented with chronic active Epstein-Barr virus (CAEBV) infection but responded poorly to treatment with ganciclovir. Next-generation sequencing (NGS) was performed, including all known PID genes, after which Sanger sequencing was performed to verify the results. Genetic analysis revealed that our patient had 2 novel compound heterozygous mutations of JAK3, a gene previously reported to cause a rare form of autosomal recessive severe combined immunodeficiency with recurrent infections. The p.H27Q mutation came from his father, while p. R222H from his mother. Thus, his diagnosis was corrected for JAK3-deficiency PID and CAEBV. Maintenance treatment of subcutaneous injection of recombinant human interferon α-2a was given to our patient with 2 MU, 3 times a week. Interferon alpha was applied and the EBV infection was gradually controlled and his symptoms ameliorated remarkably. Our patient is in good health now and did not have relapses. The diagnoses of PID should be taken into consideration when CAEBV patients respond poorly to conventional treatments. Good results of our patient indicate that interferon α-2a may be an alternative treatment for those who are unwilling to accept hematopoietic stem cell transplantation (HSCT) like our patient. Literature review identified 59 additional cases of JAK3 deficiency with various infections.

  11. Retinopathy in a patient with acute Epstein-Barr virus infection: follow-up analysis using spectral domain optical coherence tomography.

    Science.gov (United States)

    Weller, Julia M; Bergua, Antonio; Mardin, Christian Y

    2015-01-01

    To describe the clinical findings, diagnostics, and differential diagnosis in a patient with retinopathy in acute systemic Epstein-Barr virus (EBV) infection. Description of the clinical course of the EBV retinopathy was based on the medical record, photographs, and visual fields of the patient. Retinal morphology was visualized using spectral domain optical coherence tomography (Heidelberg Engineering), and fluorescein angiography. Multiple serologic tests were performed to exclude different infectious agents. A 30-year-old male patient presented with a focal scotoma in his right visual field. One week ago, he suffered from high fever, joint pain, neck stiffness, and hepatitis; 2 weeks later, he had returned from a trip to Malaysia. Visual acuity was 20/20 in both eyes. Fundoscopy showed a paravascular sharp-edged white lesion with a corresponding crescent-shaped retinal nerve fiber defect. Serology revealed high titers for EBV immunoglobulin M (IgM), but no EBV immunoglobulin G (IgG), indicating an acute infectious mononucleosis. Other reasons for noninfectious or infectious retinochoroiditis including tropical microorganisms could be excluded serologically and by imaging. Treatment with systemic acyclovir and prednisolone acetate eye drops was initiated leading to recovery of systemic and ocular findings. Acute systemic EBV infection can affect the retina leading to focal thickening of the inner retinal layers because of focal microinfarction (cotton-wool spot) or focal infectious infiltration. Spectral domain optical coherence tomography is capable of detecting changes in retinal morphology in such cases.

  12. Valutazione del nuovo sistema automatizzato Triturus - Grifols nella diagnosi sierologica delle infezioni da complesso ToRCH e da virus di Epstein Barr

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    Monica Sparacino

    2003-03-01

    Full Text Available The laboratory diagnosis of infections belonging to the ToRCH complex is mainly based of the determination of the immune status to each individual microrganism. In this report, the diagnostic performance of a new automated EIA plates processor system (SeraQuest - GRIFOLS, Pisa, Italy has been compared with other automaed methods: Enzygnost (Dade behring, Marburg, Germany, EIA Well (RADIM, Pomezia, Italy,VIDAS (bioMériuex, Marcy l’etoile, France. In addition, the diagnostic performance of SeraQuest has also been evaluated for the detection of specific immune response to Epstein Barr virus, in comparison with a conventional EIA test (Delta, Pomezia, Italy and with an immunoblotting method (Genelabs - AlfaBiotech, Milan, Italy.The overal evaluation of SeraQuest demonstrated that this test has sensitivity and specificity well comaparable with those of the other methods studied and that could be used as an alternative test in the serological diagnosis of ToRCH and EBV infections.

  13. Chronic lymphocytic leukemia/small lymphocytic lymphoma with Reed-Sternberg-like cells and possible transformation to Hodgkin's disease. Mediation by Epstein-Barr virus.

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    Momose, H; Jaffe, E S; Shin, S S; Chen, Y Y; Weiss, L M

    1992-09-01

    The pathogenesis of Reed-Sternberg cells and variants (RS-H cells) found in rare cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is unknown. We studied 13 such cases by immunohistochemistry and in situ hybridization for identification of Epstein-Barr virus (EBV) RNA. The RS-H cells in five cases expressed the B-lineage marker CD20 and were negative for CD15. In two cases, the RS-H cells showed expression of both CD20 and CD15, whereas in another six cases, the cells were positive for CD15 but negative for CD20. Three of the cases expressing CD15 showed subsequent evidence of disseminated Hodgkin's disease. Regardless of the phenotype or clinical behavior, the RS-H cells in 12 of 13 cases were found to contain EBV RNA by in situ hybridization, but the surrounding neoplastic lymphocytes were invariably negative for EBV RNA. It is suggested that EBV has an important role in the pathogenesis of the RS-H cells in these rare cases.

  14. Acute Acalculous Cholecystitis: A Rare Presentation of Primary Epstein-Barr Virus Infection in Adults—Case Report and Review of the Literature

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    Zuhal Yesilbag

    2017-01-01

    Full Text Available Primary Epstein-Barr virus (EBV infection is almost always a self-limited disease characterized by sore throat, fever, and lymphadenopathy. Hepatic involvement is usually characterized by mild elevations of aminotransferases and resolves spontaneously. Although isolated gallbladder wall thickness has been reported in these patients, acute acalculous cholecystitis is an atypical presentation of primary EBV infection. We presented a young women admitted with a 10-day history of fever, nausea, malaise who had jaundice and right upper quadrant tenderness on the physical examination. Based on diagnostic laboratory tests and abdominal ultrasonographic findings, cholestasis and acute acalculous cholecystitis were diagnosed. Serology performed for EBV revealed the acute EBV infection. Symptoms and clinical course gradually improved with the conservative therapy, and at the 1-month follow-up laboratory findings were normal. We reviewed 16 adult cases with EBV-associated AAC in the literature. Classic symptoms of EBV infection were not predominant and all cases experienced gastrointestinal symptoms. Only one patient underwent surgery and all other patients recovered with conservative therapy. The development of AAC should be kept in mind in patients with cholestatic hepatitis due to EBV infection to avoid unnecessary surgical therapy and overuse of antibiotics.

  15. Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens.

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    Cynthia J Snider

    Full Text Available Plasmodium falciparum malaria (Pf-malaria and Epstein Barr Virus (EBV infections coexist in children at risk for endemic Burkitt's lymphoma (eBL; yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years in Kenya from 2002-2004. Prevalence ratios (PR and 95% confidence intervals (CI were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5-9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30-0.99. Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5-9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology.

  16. Elevated Levels of Interferon-γ Are Associated with High Levels of Epstein-Barr Virus Reactivation in Patients with the Intestinal Type of Gastric Cancer

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    María G. Cárdenas-Mondragón

    2017-01-01

    Full Text Available Background. The inflammatory response directed against Helicobacter pylori (HP is believed to be one of the main triggers of the appearance of gastric lesions and their progression to gastric cancer (GC. Epstein-Barr virus (EBV has been found responsible for about 10% of all GCs, but the inflammatory response has not been studied in GC patients with evidence of high levels of EBV reactivation. Objective. To determine the relationship between inflammation and antibodies against EBV reactivation antigens, HP, and the bacterium virulence factor CagA in patients with GC. Methods. 127 GC patients, 46 gastritis patients, and 197 healthy subjects were studied. IL-1β, IL-6, IL-8, IL-10, TNF-α, TGF-β, MCP-1, and IFN-γ levels were measured in serum or plasma and compared against the antibody titers of VCA-IgG, HP, and the HP virulence factor CagA. Statistical associations were estimated. Results. Significant ORs and positive trends were found between VCA-IgG and IFN-γ, specifically for patients with GC of intestinal type (OR: 6.4, 95% C.I. 1.2–35.4 (p<0.044. Conclusions. We confirmed a positive association between a marker of EBV reactivation and intestinal gastric cancer and present evidence of a correlation with elevated serum levels of IFN-γ, but not with the other cytokines.

  17. Polymerase chain reaction genotyping of Epstein-Barr virus in scraping samples of the tongue lateral border in HIV-1 seropositive patients

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    TF Robaina

    2008-06-01

    Full Text Available The Epstein-Barr virus (EBV is the etiological agent of oral hairy leukoplakia (OHL, an oral lesion with important diagnostic and prognostic value in acquired immunodeficiency disease syndrome. The two EBV genotypes, EBV-1 and EBV-2, can be distinguished by divergent gene sequences encoding the EBNA-2, 3A, 3B, and 3C proteins. The purpose of this study was to identify the EBV genotype prevalent in 53 samples of scrapings from the lateral border of the tongue of HIV-1 seropositive patients, with and without OHL, and to correlate the genotypes with presence of clinical or subclinical OHL with the clinic data collected. EBV-1 and EBV-2 were identified through PCR and Nested-PCR based on sequence differences of the EBNA-2 gene. EBV-1 was identified in the 31 samples (15 without OHL, 7 with clinical OHL and 9 with subclinical OHL, EBV-2 in 12 samples (10 without OHL, 1 with clinical and 1 subclinical OHL, and a mixed infection in 10 samples (2 without OHL, 3 with clinical and 5 with subclinical OHL. The presence of EBV-1 was higher in women, but a significant statistical result relating one the EBV genotypes to the development of OHL was not found. We conclude that the oral epithelium in HIV-1 seropositive patients can be infected by EBV-1, EBV-2 or by a mixed viral population.

  18. Quantitative detection of epstein-barr virus DNA in cerebrospinal fluid and blood samples of patients with relapsing-remitting multiple sclerosis.

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    Clementina E Cocuzza

    Full Text Available The presence of Epstein-Barr Virus (EBV DNA in cerebrospinal fluid (CSF and peripheral blood (PB samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.

  19. Epstein-Barr Virus-Positive Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue in the Posttransplant Setting: An Immunodeficiency-Related (Posttransplant) Lymphoproliferative Disorder?

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    Cassidy, Daniel P; Vega, Francisco; Chapman, Jennifer R

    2017-12-20

    Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of hematolymphoid proliferations arising in the context of chronic immunosuppression. The common and indolent B-cell lymphomas, including extranodal marginal zone lymphomas (ENMZLs) of mucosa-associated lymphoid tissue (MALT), are excluded from the category of PTLD in the current World Health Organization classification. We report a case of Epstein-Barr virus (EBV)-positive bronchial-associated lymphoid tissue (BALT) lymphoma involving the lungs of a transplant patient. Aside from history of cardiac transplant, young patient age, and EBV positivity, the histopathologic findings were indistinguishable from usual BALT lymphoma. We review the literature of ENMZL occurring in immunocompromised patients and present this case for consideration that this specific entity is a PTLD. We believe that additional studies might lend strength to the hypothesis that this particular group of EBV-positive, posttransplant ENMZLs merits classification and management as PTLDs. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  20. Translational profiling of B cells infected with the Epstein-Barr virus reveals 5' leader ribosome recruitment through upstream open reading frames.

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    Bencun, Maja; Klinke, Olaf; Hotz-Wagenblatt, Agnes; Klaus, Severina; Tsai, Ming-Han; Poirey, Remy; Delecluse, Henri-Jacques

    2018-02-26

    The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs. A similar process was visible for a subset of lytic genes including the key transactivators BZLF1 and BRLF1 in cells infected with weakly replicating EBV strains. This suggests that ribosome trapping, particularly in the leader region, represents a new checkpoint for the repression of lytic replication. We could identify 25 upstream open reading frames (uORFs) located upstream of coding transcripts that displayed 5' leader ribosome trapping, six of which were located in the leader region shared by many latent transcripts. These uORFs repressed viral translation and are likely to play an important role in the regulation of EBV translation.

  1. Ascorbic Acid Kills Epstein-Barr Virus (EBV) Positive Burkitt Lymphoma Cells and EBV Transformed B-Cells in Vitro, but not in Vivo

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    Shatzer, Amber N.; Espey, Michael G.; Chavez, Mayra; Tu, Hongbin; Levine, Mark; Cohen, Jeffrey I.

    2014-01-01

    Ascorbic acid has been shown to kill various cancer cell lines at pharmacologic concentrations. We found that Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) cells were more susceptible to ascorbic acid-induced cell killing than EBV-negative BL cells or EBV-transformed lymphoblastoid cells (LCLs). Ascorbic acid did not induce apoptosis in any of the tested cells but did induce the production of reactive oxygen species and cell death. Previously, we showed that bortezomib, a proteasome inhibitor, induces cell death in LCLs and EBV-positive BL cells. We found that ascorbic acid is strongly antagonistic for ascorbic acid-induced cell death in LCLs and EBV-positive BL cells. Finally, ascorbic acid did not prolong survival of severe combined immunodefiency mice inoculated with LCLs either intraperitoneally or subcutaneously. Thus, while ascorbic acid was highly effective at killing EBV-positive BL cells and LCLs in vitro, it antagonized cell killing by bortezomib and was ineffective in an animal model. PMID:23067008

  2. Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca2+/calpain/ITGβ4 axis

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    Jiezhen Liang

    2017-06-01

    Full Text Available Epstein-Barr virus (EBV-encoded latent membrane protein 2A (LMP2A promotes the motility of nasopharyngeal carcinoma (NPC cells. Previously, we have shown that the localization of integrin β4 (ITGβ4 is regulated by LMP2A, with ITGβ4 concentrated at the cellular protrusions in LMP2A-expressing NPC cells. In the present study, we aim to further investigate mechanisms involved in this process and its contribution to cell motility. We show that expression of LMP2A was correlated with increased epidermal growth factor receptor (EGFR activation, elevated levels of intracellular Ca2+, calpain activation and accelerated cleavage of ITGβ4. Activation of EGFR and calpain activity was responsible for a redistribution of ITGβ4 from the basal layer of NPC cells to peripheral membrane structures, which correlated with an increased migratory capacity of NPC cells. Furthermore, we demonstrated that the calpain inhibitor calpastatin was downregulated in NPC primary tumors. In conclusion, our results point to LMP2A-mediated targeting of the EGFR/Ca2+/calpain/ITGβ4 signaling system as a mechanism underlying the increased motility of NPC cells. We suggest that calpain-facilitated cleavage of ITGβ4 contributes to the malignant phenotype of NPC cells.

  3. Heat shock factor 1 upregulates transcription of Epstein-Barr Virus nuclear antigen 1 by binding to a heat shock element within the BamHI-Q promoter

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    Wang, Feng-Wei [The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Wu, Xian-Rui [Department of Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou (China); Liu, Wen-Ju; Liao, Yi-Ji [The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Lin, Sheng [Laboratory of Integrated Biosciences, School of Life Science, Sun Yat-sen University, Guangzhou (China); Zong, Yong-Sheng; Zeng, Mu-Sheng; Zeng, Yi-Xin [The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Mai, Shi-Juan, E-mail: maishj@sysucc.org.cn [The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Xie, Dan, E-mail: xied@mail.sysu.edu.cn [The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou (China)

    2011-12-20

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for maintenance of the episome and establishment of latency. In this study, we observed that heat treatment effectively induced EBNA1 transcription in EBV-transformed B95-8 and human LCL cell lines. Although Cp is considered as the sole promoter used for the expression of EBNA1 transcripts in the lymphoblastoid cell lines, the RT-PCR results showed that the EBNA1 transcripts induced by heat treatment arise from Qp-initiated transcripts. Using bioinformatics, a high affinity and functional heat shock factor 1 (HSF1)-binding element within the - 17/+4 oligonucleotide of the Qp was found, and was determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Moreover, heat shock and exogenous HSF1 expression induced Qp activity in reporter assays. Further, RNA interference-mediated HSF1 gene silencing attenuated heat-induced EBNA1 expression in B95-8 cells. These results provide evidence that EBNA1 is a new target for the transcription factor HSF1.

  4. Detection and quantification of Epstein-Barr virus EBER1 in EBV-infected cells by fluorescent in situ hybridization and flow cytometry

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    Stowe, R. P.; Cubbage, M. L.; Sams, C. F.; Pierson, D. L.; Barrett, A. D.

    1998-01-01

    A rapid and highly sensitive fluorescent in situ hybridization (FISH) assay was developed to detect Epstein Barr virus (EBV)-infected cells in peripheral blood. Multiple fluorescein-labeled antisense oligonucleotide probes were designed to hybridize to the EBER1 transcript, which is highly expressed in latently infected cells. After a rapid (30 min) hybridization, the cells were analyzed by flow cytometry. EBER1 was detected in several positive control cell lines that have variable numbers of EBV genome copies. No EBER1 was detected in two known EBV-negative cell lines. Northern blot analyses confirmed the presence and quantity of EBER1 transcripts in each cell line. This method was used to quantify the number of EBV-infected cells in peripheral blood from a patient with chronic mononucleosis. These results indicate that EBV-infected cells can be detected at the single cell level, and that this assay can be used to quantify the number of EBV-infected cells in clinical samples.

  5. Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton's tyrosine kinase and STAT3.

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    Incrocci, Ryan; Barse, Levi; Stone, Amanda; Vagvala, Sai; Montesano, Michael; Subramaniam, Vijay; Swanson-Mungerson, Michelle

    2017-01-01

    Previous data demonstrate that Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 to promote the survival of LMP2A-expressing B cell lymphomas. Since STAT3 is an important regulator of IL-10 production, we hypothesized that LMP2A activates a signal transduction cascade that increases STAT3 phosphorylation to enhance IL-10. Using LMP2A-negative and -positive B cell lines, the data indicate that LMP2A requires the early signaling molecules of the Syk/RAS/PI3K pathway to increase IL-10. Additional studies indicate that the PI3K-regulated kinase, BTK, is responsible for phosphorylating STAT3, which ultimately mediates the LMP2A-dependent increase in IL-10. These data are the first to show that LMP2A signaling results in STAT3 phosphorylation in B cells through a PI3K/BTK-dependent pathway. With the use of BTK and STAT3 inhibitors to treat B cell lymphomas in clinical trials, these findings highlight the possibility of using new pharmaceutical approaches to treat EBV-associated lymphomas that express LMP2A. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Establishment and characterization of a novel Hodgkin lymphoma cell line, AM-HLH, carrying the Epstein-Barr virus genome integrated into the host chromosome.

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    Hayashida, Masahiko; Daibata, Masanori; Tagami, Erika; Taguchi, Takahiro; Maekawa, Fumiyo; Takeoka, Kayo; Fukutsuka, Katsuhiro; Shimomura, Daiki; Hayashi, Takamasa; Iwatani, Yoshinori; Ohno, Hitoshi

    2017-12-01

    We describe the establishment and characterization of a cell line, AM-HLH, obtained from a patient with Epstein-Barr virus-positive (EBV + ) nodular sclerosis-type Hodgkin lymphoma (HL). The cells were positive for CD2 and CD30 and negative for CD15. The immunoglobulin heavy- and κ light-chain genes were rearranged. The karyotype was of the triploid range. Southern blotting using the EBV terminal repeat probe detected 3 hybridizing bands that were identical to those of the parental HL material. The cells expressed EBV-encoded RNAs as well as latent genes (EBNA1, EBNA2, LMP1, and LMP2A) and lytic genes (BZLF1 and BALF2). Fluorescence in situ hybridization (FISH) with the cosmid pJB8 clone containing a fragment of EBV DNA as a probe revealed multiple hybridization signals at a marker chromosome. Additional FISH using whole chromosome painting and centromere probes in combination with multicolor FISH determined that multiple EBV copies were clustered within the chromosome 20 materials of the marker chromosome. Culture supernatants of AM-HLH contained IL-10 as measured by the bead-based immunoassay. It is possible that an integrated EBV genome and cellular genes on chromosome 20 were coamplified, leading to the enhanced expression of genes involved in cell growth control. The AM-HLH cell line will be useful to clarify the role of cytokines in the development of EBV + HL. Copyright © 2016 John Wiley & Sons, Ltd.

  7. The role of the early social environment on Epstein Barr virus infection: a prospective observational design using the Millennium Cohort Study.

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    Gares, V; Panico, L; Castagne, R; Delpierre, C; Kelly-Irving, M

    2017-12-01

    Epstein-Barr virus (EBV) is a highly prevalent herpesvirus linked to infectious mononucleosis and several malignancies. This paper aims to study the association between children's early life social environment at 9 months and EBV infection at 3 years of age. We used data on children included in the UK Millennium Cohort Study. We described the social environment using area-level and material factors as well as socioeconomic position (SEP) at 9 months. EBV was measured at 3 years of age (n = 12 457). Lower rates of EBV infection were observed in children living in towns and rural areas compared with those living in cities. Lower SEP and overcrowding in the household increased the odds of being infected. Children whose parents were social tenants were more likely to be infected than homeowners. In the overall model, the strength of the association between material factors and EBV infection weakened. We showed that early life material deprivation was associated with a higher risk of EBV infection among 3-year-olds. Children living in more deprived social conditions may be more likely to become EBV carriers at an earlier age.

  8. Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

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    Trier, Nicole; Izarzugaza, Jose; Chailyan, Anna; Marcatili, Paolo; Houen, Gunnar

    2018-01-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cell