scholarly journals Characterization and Establishment of a Novel EBV Strain Simultaneously Associated With Nasopharyngeal Carcinoma and B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fenggang Yu ◽  
Nicholas L. Syn ◽  
Yanan Lu ◽  
Qing Yun Chong ◽  
Junyun Lai ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Phylogenetic Analyses ◽  
Human Tumor ◽  
B Cell Lymphoma ◽  
Asia Pacific ◽  
B Lymphoma ◽  
Barr Virus ◽  
Molecular Features ◽  
Geographical Regions ◽  
Epstein Barr

Epstein-Barr virus (EBV)—the prototypical human tumor virus—is responsible for 1–2% of the global cancer burden, but divergent strains seem to exist in different geographical regions with distinct predilections for causing lymphoid or epithelial malignancies. Here we report the establishment and characterization of Yu103, an Asia Pacific EBV strain with a highly remarkable provenance of being derived from nasopharyngeal carcinoma biopsy but subsequently propagated in human B-lymphoma cells and xenograft models. Unlike previously characterized EBV strains which are either predominantly B-lymphotropic or epitheliotropic, Yu103 evinces an uncanny capacity to infect and transform both B-lymphocytes and nasopharyngeal epithelial cells. Genomic and phylogenetic analyses indicated that Yu103 EBV lies midway along the spectrum of EBV strains known to drive lymphomagenesis or carcinogenesis, and harbors molecular features which likely account for its unusual properties. To our knowledge, Yu103 EBV is currently the only EBV isolate shown to drive human nasopharyngeal carcinoma and B-lymphoma, and should therefore provide a powerful novel platform for research on EBV-driven hematological and epithelial malignancies.

scholarly journals Characterization and establishment of a novel EBV strain simultaneously associated with nasopharyngeal carcinoma and B-cell lymphoma

2020 ◽  
Author(s):  
Fenggang Yu ◽  
Nicholas L. Syn ◽  
Yanan Lu ◽  
Qing Yun Chong ◽  
Junyun Lai ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Phylogenetic Analyses ◽  
Human Tumor ◽  
B Cell Lymphoma ◽  
Asia Pacific ◽  
B Lymphoma ◽  
Barr Virus ◽  
Molecular Features ◽  
Geographical Regions ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus (EBV) – the prototypical human tumor virus – is responsible for 1-2% of the global cancer burden, but divergent strains seem to exist in different geographical regions with distinct predilections for causing lymphoid or epithelial malignancies. Here we report the establishment and characterization of Yu103, an Asia Pacific EBV strain with a highly remarkable provenance of being derived from nasopharyngeal carcinoma biopsy but subsequently propagated in human B-lymphoma cells and xenograft models. Unlike previously characterized EBV strains which are either predominantly B-lymphotropic or epitheliotropic, Yu103 evinces an uncanny capacity to infect and transform both B-lymphocytes and nasopharyngeal epithelial cells. Genomic and phylogenetic analyses indicated that Yu103 EBV lies midway along the spectrum of EBV strains known to drive lymphomagenesis or carcinogenesis, and harbors molecular features which likely account for its unusual properties. To our knowledge, Yu103 EBV is currently the only EBV isolate shown to drive human nasopharyngeal carcinoma and B-lymphoma, and should therefore provide a powerful novel platform for research on EBV-driven hematological and epithelial malignancies.

scholarly journals Prevalence of Epstein Barr Virus in biopsy specimens of nasopharyngeal carcinoma from Serbian patients

2014 ◽  
Vol 66 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Ana Banko ◽  
Ivana Lazarevic ◽  
M. Folic ◽  
Maja Cupic ◽  
Tanja Jovanovic
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Biopsy Specimens ◽  
C Terminus ◽  
Geographical Regions ◽  
Significant Difference ◽  
Ebv Dna ◽  
Epstein Barr

The development of nasopharyngeal carcinoma (NPC) is the result of interaction between Epstein-Barr Virus (EBV) and many non-viral factors. The aims of this study were to determine the prevalence of EBV in NPC biopsies from Serbian patients and to investigate the correlation between EBV presence and demographic, anamnestic and clinical data. Ninety-three tissue blocks were included. For detection of EBV DNA, the C terminus of the LMP1 gene was amplified by nested-PCR. Twenty-eight biopsies were EBV-DNA-positive (30.1%), with a statistically significant difference in EBV DNA presence between geographical regions (p=0.02) and between the stages of tumor-node-metastasis (TNM) (p=0.02). A correlation was also found with the presence of EBV DNA and smoking (p=0.02). The correlation of EBV DNA presence, with or without smoking and the promising outcome of the disease was statistically significant (p=0.02; p=0.01). The EBV DNA findings from this study confirm the role of EBV in NPC carcinogenesis, and show the different distribution among TNM stages and correlation between the virus and outcome of disease.

scholarly journals Genetic Subgroups Inform on Pathobiology in Adult and Pediatric Burkitt Lymphoma

2021 ◽  
Author(s):  
Nicole Thomas ◽  
Kostiantyn Dreval ◽  
Daniela S. Gerhard ◽  
Laura K. Hilton ◽  
Jeremy S. Abramson ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Somatic Hypermutation ◽  
B Cell Lymphoma ◽  
Epidemiological Studies ◽  
Sub Saharan Africa ◽  
Driver Mutations ◽  
Barr Virus ◽  
Molecular Features ◽  
Genetic Features ◽  
Epstein Barr

AbstractBurkitt lymphoma (BL) accounts for the majority of pediatric non-Hodgkin lymphomas (NHL) and is relatively rare but significantly more lethal when diagnosed in adults. The global incidence is highest in Sub-Saharan Africa, where Epstein-Barr virus (EBV) positivity is observed in 95% of all tumors. Both pediatric (pBL) and adult (aBL) cases are known to share some driver mutations, for example MYC translocations, which are seen in > 90% of cases. Sequencing efforts have identified many common somatic alterations that cooperate with MYC in lymphomagenesis with approximately 30 significantly mutated genes (SMG) reported thus far. Recent analyses revealed non-coding mutation patterns in pBL that were attributed to aberrant somatic hypermutation (aSHM). We sought to identify genomic and molecular features that may explain clinical disparities within and between aBL and pBL in an effort to delineate BL subtypes that may allow for the stratification of patients with shared pathobiology. Through comprehensive sequencing of BL genomes, we found additional SMGs, including more genetic features that associate with tumor EBV status, and established three new genetic subgroups that span pBL and aBL. Direct comparisons between pBL and aBL revealed only marginal differences and the mutational profiles were consistently better explained by EBV status. Using an unsupervised clustering approach to identify subgroupings within BL and diffuse large B-cell lymphoma (DLBCL), we have defined three genetic subgroups that predominantly comprise BL tumors. Akin to the recently defined DLBCL subgroups, each BL subgroup is characterized by combinations of common driver mutations and non-coding mutations caused by aSHM. Two of these subgroups and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among the aBL and pBL cohorts. These findings highlight not only a shared pathogenesis between aBL and pBL, but also establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiological studies, and diagnostic and therapeutic strategies.

scholarly journals INFECTIONS CAUSED BY EPSTEIN-BARR VIRUS IN HIV-INFECTED PATIENTS

2016 ◽  
pp. 108-116
Author(s):  
L. V. Puzyreva ◽  
A. D. Safonov
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
B Cell ◽  
Interstitial Pneumonitis ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
Clinical Manifestations ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Epstein Barr ◽  
Hodgkin's Lymphomas

The review is dedicated to features of clinical manifestations of infections caused by Epstein-Barr virus (EBV) in HIV-infected patients, problems of diagnostics and execution of antiviral therapy in the case of combination of these infections. Individuals at AIDS stage develop tumors, associated with EBV: non-Hodgkin’s lymphomas, including Berkitt’s lymphoma, primary B-cell lymphoma ofCNS, nasopharyngeal carcinoma. Formation of lymphoid interstitial pneumonitis and leukoplakia is known to be associated with EBV. A large list of preparations that are inhibitors of EBV replication are currently known, however, there is no clear pathogenetically justified therapy scheme for patients with this infection against the background of HIV-infection.

scholarly journals Sequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage, and Diseases

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Samantha Correia ◽  
Ray Bridges ◽  
Fanny Wegner ◽  
Cristina Venturini ◽  
Anne Palser ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Codon Usage ◽  
Epstein Barr Virus ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disease ◽  
Lytic Cycle ◽  
Multiple Sequence ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACTOne hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. One hundred twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type 2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART microRNA region of the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with chronic active EBV infection aligned with the wild-type EBV genome with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes, and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCEEpstein-Barr virus causes most cases of infectious mononucleosis and posttransplant lymphoproliferative disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions, and differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV-associated cancers are already known, and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets.

scholarly journals Pathobiology of Hodgkin Lymphoma

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Pier Paolo Piccaluga ◽  
Claudio Agostinelli ◽  
Anna Gazzola ◽  
Claudio Tripodo ◽  
Francesco Bacci ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Molecular Characteristics ◽  
Epstein Barr Virus Infection ◽  
Research Activity ◽  
Barr Virus ◽  
Molecular Features ◽  
Epstein Barr

Despite its well-known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B-cell derivation of the tumor in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognizes a basic distinction between lymphocyte predominance HL (LP-HL) and classic HL (cHL), reflecting the differences in clinical presentation and behavior, morphology, phenotype, and molecular features. cHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between cHL and anaplastic large-cell lymphoma have become sharper, whereas those between LP-HL and T-cell-rich B-cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumor in at-risk patients have been proposed and are on the way to being applied.

scholarly journals CircEAF2 counteracts Epstein-Barr virus-positive diffuse large B-cell lymphoma progression via miR-BART19-3p/APC/β-catenin axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chen-xing Zhao ◽  
Zi-xun Yan ◽  
Jing-jing Wen ◽  
Di Fu ◽  
Peng-peng Xu ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
B Lymphoma ◽  
Barr Virus ◽  
Ebv Infection ◽  
Large B Cell Lymphoma ◽  
Epstein Barr ◽  
Large B Cell

Abstract Background Epstein-Barr virus (EBV) represents an important pathogenic factor of lymphoma and is significantly associated with poor clinical outcome of diffuse large B-cell lymphoma (DLBCL). Circular RNAs (circRNAs) play an essential role in lymphoma progression. However, the underlying mechanism of circRNA on DLBCL progression related to EBV remains largely unknown. Methods CircRNA was screened by high-throughput sequencing in tumor samples of 12 patients with DLBCL according to EBV infection status. Expression of circEAF2, as well as the relationship with clinical characteristics and prognosis, were further analyzed in tumor samples of 100 DLBCL patients using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of circEAF2 both in vitro and in vivo. The underlying mechanism of circRNA on DLBCL progression were further determined by RNA sequencing, RNA pull down assay, dual-luciferase reporter assay, rescue experiments and western blotting. Results We identified a novel circRNA circEAF2, which was downregulated in EBV + DLBCL and negatively correlated with EBV infection and DLBCL progression. In EBV-positive B lymphoma cells, circEAF2 overexpression induced lymphoma cell apoptosis and sensitized lymphoma cells to epirubicin. As mechanism of action, circEAF2 specifically targeted EBV-encoded miR-BART19-3p, upregulated APC, and suppressed downstream β-catenin expression, resulting in inactivation of Wnt signaling pathway and inhibition of EBV + DLBCL cell proliferation. In EBV-positive B-lymphoma murine models, xenografted tumors with circEAF2 overexpression presented decreased Ki-67 positivity, increased cell apoptosis and retarded tumor growth. Conclusions CircEAF2 counteracted EBV + DLBCL progression via miR-BART19-3p/APC/β-catenin axis, referring circEAF2 as a potential prognostic biomarker. Therapeutic targeting EBV-encoded miRNA may be a promising strategy in treating EBV-associated lymphoid malignancies.

Studies of Epstein-Barr Virus Antigens Using Immunoperoxidase and Immunofluorescence Techniques

1975 ◽  
Vol 33 ◽  
pp. 342-343
Author(s):  
R. Stephens ◽  
K. Traul ◽  
D. Woolf ◽  
P. Gaudreau
Keyword(s):  
Electron Microscopy ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
If Technique ◽  
Infected Cells ◽  
Virus Antigens ◽  
Epstein Barr ◽  
Virus Capsid Antigen ◽  
Antigen Reactivity

A number of antigens have been found associated with persistent EBV infections of lymphoblastoid cells. Identification and localization of these antigens were principally by immunofluorescence (IF) techniques using sera from patients with nasopharyngeal carcinoma (NPC), Burkitt lymphoma (BL), and infectious mononucleosis (IM). Our study was mainly with three of the EBV related antigens, a) virus capsid antigen (VCA), b) membrane antigen (MA), and c) early antigens (EA) using immunoperoxidase (IP) techniques with electron microscopy (EM) to elucidate the sites of reactivity with EBV and EBV infected cells.Prior to labeling with horseradish peroxidase (HRP), sera from NPC, IM, and BL cases were characterized for various reactivities by the indirect IF technique. Modifications of the direct IP procedure described by Shabo and the indirect IP procedure of Leduc were made to enhance penetration of the cells and preservation of antigen reactivity.

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