Epstein-Barr Virus Infection Is Not the Sole Cause of High Prevalence for Hodgkin’s Lymphoma in Saudi Arabia.

Abstract Age adjusted incidence of Hodgkin’s Lymphoma (HL) is markedly higher in Saudi Arabia than in the United States. For example, HL accounts for 10.5% of all neoplasia in children 15 years and younger in Saudi Arabia. EBV virus infection, which can induce HL transformation has been suspected to cause high HL incidence in developing countries. To investigate the role of EBV for the high frequency of HL in Saudi Arabia, we analyzed 265 HL from Saudi Arabia and 58 HL from Europe for EBV infection by in situ hybridization with fluoresce in-conjugated Epstein-Barr virus (EBER) on tissue microarray (TMA) sections. All Saudi and European HL were analyzed in one staining run under identical conditions. Unexpectedly, our data show only minor, statistically insignificant differences in EBV infection rates between Saudi (64 out of 150 informative cases; 42.6%) and European HL (11 out of 30 informative cases; 33%; p=0.5). Within the Arabian population, EBV positivity was more frequent in 79 children (53%) than among 133 adults (36%; p=0.015). EBV positivity was also linked to high stage with EBV positivity in 36% of 69 stage I/II and 64% of 73 stage III/IV tumors (p=0.009). EBV infection was most frequently seen in mixed cellularity HL (63% of 27 cases). This was significantly more frequent than in nodular sclerosing HL (39% of 136; p=0.02). Interestingly, EBV positivity was associated with good prognosis in Saudi childhood HL (p=0.016) but with poor prognosis in Saudi adulthood HL (p=0.0048). In conclusion, our data strongly suggest that EBV is not the main cause for the high prevalence of HL in Middle East countries. Among others, this would be consistent with a major role of genetic susceptibility genes for HL in these populations. Saudi Arabia with high consanguinity and large families would be ideal to search for HL susceptibility genes.

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Epstein – Barr virus infection is not the sole cause of high prevalence for Hodgkin's lymphoma in Saudi Arabia

Leukemia & Lymphoma ◽

10.1080/10428190500286879 ◽

2006 ◽

Vol 47 (4) ◽

pp. 707-713 ◽

Cited By ~ 7

Author(s):

Khawla Al-Kuraya ◽

Rajeswari Narayanappa ◽

Fouad Al-Dayel ◽

Hassan El-Solh ◽

Adnan Ezzat ◽

...

Keyword(s):

Saudi Arabia ◽

Virus Infection ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

High Prevalence ◽

Epstein Barr ◽

Barr Virus Infection

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Common Epstein-Barr virus (EBV) type-1 variant strains in both malignant and benign EBV-associated disorders

Blood ◽

10.1182/blood.v87.4.1579.bloodjournal8741579 ◽

1996 ◽

Vol 87 (4) ◽

pp. 1579-1585 ◽

Cited By ~ 24

Author(s):

V Schuster ◽

G Ott ◽

S Seidenspinner ◽

HW Kreth

Keyword(s):

Gastric Carcinoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Sequence Pattern ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr

In the present study, Epstein-Barr virus (EBV) isolates from 18 malignant tumors (angioimmunoblastic lymphadenopathy [AILD], n = 4; Hodgkin's disease [HD], n = 3; pleomorphic T-cell non-Hodgkin's lymphoma [T-NHL], n = 1; B-cell non-Hodgkin's lymphoma [B-NHL], n = 8; gastric carcinoma, n = 2) as well as from 10 tonsils of EBV- seropositive children and from peripheral blood mononuclear cells of 12 children with uncomplicated infectious mononucleosis (IM) and of a boy with severe chronic active EBV infection were genotyped in the EBV nuclear antigen-2 (EBNA-2) gene. A total of 40 of 41 isolates harbored EBV type 1; in 1 specimen (tonsil), only EBV type 2 was found. Further molecular characterization of EBV type-1 wild-type isolates in the EBNA- 2 gene and in the 40-kb distant EBV-encoded small RNAs (EBER) region showed that different groups of stable EBV type-1 variant strains exist in vivo both in benign and malignant lymphatic tissue. Group 1 is composed of EBV type-1 isolates (B-NHL, n = 3; T-NHL, n = 1; HD, n = 1; IM, n = 4) that showed a B95–8-like DNA sequence pattern in both viral genes. Group 2 isolates (HD, n = 1; AILD, n = B-NHL, n = 1; tonsils of EBV-seropositive children, n = 9; IM, n = 20 showed a nucleotide change at position 49095 in the EBNA-2 gene, leading to an amino acid substitution (Pro-->Ser), and EBV type-2 sequences in the EBER region. EBV type-1 isolates that fall into group 3 (AILD, n = 3; HD, n = 1; B- NHL, n = 4; gastric carcinoma, n = 2; IM, n = 6; severe chronic active EBV infection, n = 1) were characterized by typical nucleotide changes and a 3-bp insertion (CTC; extra Leu residue) in the EBNA-2 gene and an EBV type-2-specific sequence pattern in the EBER region. These EBV type- 1 variant strains may represent the most prevalent circulating EBV type- 1 strains in the exposed population and seem not to be restricted to a certain EBV-associated disease or tumor type. However, analysis of more EBV isolates from benign and malignant lesions must show whether more EBV type-1 substrains exist in vivo.

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The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.3121.3121 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3121-3121

Author(s):

Alexander Claviez ◽

Markus Tiemann ◽

Heike Lueders ◽

Reza Parwaresch ◽

Guenther Schellong ◽

...

Keyword(s):

Overall Survival ◽

Children And Adolescents ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Barr Virus ◽

Ebv Infection ◽

Nodular Sclerosis ◽

Epstein Barr ◽

The Impact

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.

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Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection

British Journal of Haematology ◽

10.1046/j.1365-2141.2000.01884.x ◽

2000 ◽

Vol 108 (2) ◽

pp. 377-382 ◽

Cited By ~ 34

Author(s):

Strahm ◽

Rittweiler ◽

Duffner ◽

Brandau ◽

Orlowska-Volk ◽

...

Keyword(s):

Virus Infection ◽

B Cell ◽

Epstein Barr Virus ◽

Lymphoproliferative Disease ◽

Hodgkin's Lymphoma ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Non Hodgkin's Lymphoma ◽

Epstein Barr ◽

Barr Virus Infection

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Interplay between the epigenetic enzyme lysine (K)-specific demethylase 2B and Epstein-Barr virus infection

10.1101/367094 ◽

2018 ◽

Cited By ~ 1

Author(s):

Romina C. Vargas-Ayala ◽

Antonin Jay ◽

Hector Hernandez-Vargas ◽

Audrey Diederichs ◽

Alexis Robitaille ◽

...

Keyword(s):

Life Cycle ◽

B Cells ◽

Virus Infection ◽

Burkitt Lymphoma ◽

Epstein Barr Virus ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Epstein Barr ◽

Barr Virus Infection

AbstractHistone modifier lysine (K)-specific demethylase 2B(KDM2B) plays a role in hematopoietic cells differentiation and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that KDM2B gene is differentially methylated in cell lines derived from the Epstein-Barr virus (EBV) associated endemic Burkitt’s lymphomas (eBL) compared to EBV negative sporadic BL cells. However, whether KDM2B plays a role in eBL development has never been previously demonstrated. Oncogenic viruses have been shown to hijack the host cell epigenome to complete their life cycle and to promote the transformation process by perturbing cell chromatin organization. Here we investigated whether EBV would alter KDM2B levels to enable its life cycle and promote B-cells transformation. We show that infection of B-cells with EBV leads to down-regulation of KDM2B levels. We also show that LMP1, one of the main EBV transforming proteins, induces increased DNMT1 recruitment to KDM2B gene and augments its methylation. By altering KDM2B levels and performing chromatin immunoprecipitation in EBV infected B-cells, we were able to show that KDM2B is recruited to the EBV gene promoters and inhibits their expression. Furthermore, forced KDM2B expression in immortalized B-cells led to altered mRNA levels of some differentiation-related genes. Our data show that EBV deregulates KDM2B levels through an epigenetic mechanism and provide evidence for a role of KDM2B in regulating virus and host cell gene expression, warranting further investigations to assess the role of KDM2B in the process of EBV-mediated lymphomagenesis.IMPORTANCE. In Africa, Epstein-Barr virus infection is associated with endemic Burkitt lymphoma, a pediatric cancer. The molecular events leading to its development are poorly understood compared to the sporadic Burkitt lymphoma. In a previous study, by analyzing the DNA methylation changes in endemic compared to sporadic Burkitt lymphomas cell lines, we identified several differential methylated genomic positions in proximity of genes with a potential role in cancer, among them the KDM2B gene. KDM2B encodes a histone H3 demethylase already shown to be involved in some hematological disorders. However, whether KDM2B plays a role in the development of Epstein-Barr virus-mediated lymphoma has never been investigated before. In this study we show that Epstein-Barr virus deregulates KDM2B expression and describe the underlying mechanisms. We also reveal a role of the demethylase in controlling viral and B-cells genes expression, thus highlighting a novel interaction between the virus and the cellular epigenome.

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Increasing Epstein-Barr virus infection in Chinese children: A single institutional based retrospective study.

F1000Research ◽

10.12688/f1000research.15544.1 ◽

2018 ◽

Vol 7 ◽

pp. 1211 ◽

Cited By ~ 1

Author(s):

Kiran Devkota ◽

Maio He ◽

Meng Yi Liu ◽

Yan Li ◽

You Wei Zhang

Keyword(s):

Retrospective Study ◽

High Risk ◽

Virus Infection ◽

Epstein Barr Virus ◽

Severe Illness ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr

The Epstein-Barr virus (EBV) is a common virus in humans and the most common causative agent of Infectious Mononucleosis. EBV primary infection has recently risen in some countries and children below 2 years of age are highly susceptible. The clinical manifestations in children with EB virus infection involve multiple systems, causing severe illness, meaning attention should be paid during diagnosis and treatment. Objective: This single institution based retrospective study was carried out with the aim of estimating the overall prevalence of EBV infection and identifying high-risk age group among children. Methods: This study include total 253 patients under 15 years of age found to be positive for EBV DNA by PCR who were admitted to the Pediatrics Department of Renmin Hospital,(Shiyan, China) during a 4-year period from 2014 to 2017. Patients were divided into three groups; 0-<4years, 4-<6years and 6-<15years. We then calculated the percentage and prevalence of EBV DNA-positive cases. Results: The yearly EBV prevalence rate was 4.99 per 1000 admissions in 2014, 6.97 per 1000 admissions in 2015, 10.42 per 1000 admissions in 2016, and 12.16 per 1000 admissions in 2017. Out of 253 EBV-positive cases, those under 4 years had the highest rate of EBV infection (74.7%). The rate drops to 11.06% in the 4-6 years group, and was 14.22% in the 6-15 years group. Those between 6 months and 1 year are those at the highest risk. Conclusion: The rate of hospital admission of children due to EBV infection is increasing day by day. Children under 4 years of age are highly susceptible to infection and children of age between 6 months and 1 year are the high-risk group for EBV infection.

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PREVALENCE OF POLYMORPHISM OF THE TLR-9 TYPE GENE IN PATIENTS WITH CHRONIC EPSTEIN-BARR VIRUS INFECTION

The Journal of V. N. Karazin Kharkiv National University, Series "Medicine" ◽

10.26565/2313-6693-2018-35-06 ◽

2018 ◽

Keyword(s):

Virus Infection ◽

Frequency Distribution ◽

Genetic Background ◽

Epstein Barr Virus ◽

Risk Groups ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Epstein Barr ◽

Barr Virus Infection

The prevalence of polymorphism -1486T/C of the TLR-9 gene was studied in 44 patients with chronic Epstein-Barr virus infection (CEBV). The control group for the study of the polymorphisms prevalence of -1486T/C of the TLR-9 gene was 40 healthy donors. Three main genotypes of -1486T/C of the TLR-9 gene were identified based on the obtained results – TT, TC, CC. Investigation of the occurrence frequency of individual genotypes revealed the dominance of the TC genotype, compared with the homozygous TT and CC genotypes. The study of -1486T/C of the TLR-9 gene polymorphism frequency distribution for different genotypes demonstrated the specificity of changes in the TC genotype in patients with CEBV and the absence of such for the TT and CC genotypes. These results confirm the important role of the TLR-mediated signaling in the pathogenesis of the disease, which is necessary to determine the genetic background associated with the course of the disease and its possible consequences. These are the aspects that will further enable the identification of risk groups among such patients and provide timely therapy. The analysis of the results of the -1486T/C polymorphism of the TLR-9 gene revealed three main genotypes –TT, TC, CC. Investigation of the occurrence frequency of individual genotypes revealed the dominance of the genotype TC, compared with the homozygous genotypes of TT and CC. The study of frequency distribution of the polymorphism -1486T/C of TLR-9 for different genotypes demonstrated the specificity of changes in the TC genotype and the absence of suchin the TT and CC genotypes in patients with CEBV.Our study for the purpose of determining the 1486T/C polymorphism of the TLR-9, that is associated with chronic forms of CEBV infection, confirms the important role of TLR-mediated signaling in the pathogenesis of this disease, which is necessary to determine the genetic background associated with the course of the disease and possible consequences of CEBV. These aspects will further enable the identification of risk groups among such patients and provide timely therapy.Analysis of the results allowed establishing the following:1. The 1486T/C polymorphism of the TLR-9 gene is significantly more frequent in patients with CEBV than in the control.2. The frequency distribution of the -1486T/C polymorphism ofthe TLR-9 gene allowed the establishment of the association of the genotype TC with chronic forms of the EBV infection, which is very specific for this group of patients.

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Epstein–Barr virus and risk of breast cancer: a systematic review and meta-analysis

Future Oncology ◽

10.2217/fon-2019-0232 ◽

2019 ◽

Vol 15 (24) ◽

pp. 2873-2885 ◽

Cited By ~ 5

Author(s):

Mohammad Farahmand ◽

Seyed Hamidreza Monavari ◽

Zabihollah Shoja ◽

Hadi Ghaffari ◽

Mehdi Tavakoli ◽

...

Keyword(s):

Breast Cancer ◽

Epstein Barr Virus ◽

Potential Role ◽

Meta Analysis ◽

Case Control ◽

Case Control Studies ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr

Despite the numerous publications regarding the role of Epstein–Barr virus (EBV) in breast cancer development, the topic has still remained controversial. The aim of the meta-analysis was to estimate the overall prevalence of EBV in the breast cancer population, and to investigate the association between EBV and breast cancer risk. The overall prevalence of EBV was calculated 26.37% (95% CI: 22–31%) from the 44 included studies. Meta-analysis of 30 case–control studies showed that the pooled association between EBV and risk of breast cancer is odds ratio 4.74 (95% CI: 2.92–7.69; Z = 6.30; p < 0.0001). Our analyses indicate a strong statistical relationship between EBV infection and risk of breast cancer, suggesting a potential role of EBV infection in the development of breast cancer.

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