scholarly journals Effects of Epstein-Barr Virus Infection on CD19+ B Lymphocytes in Patients with Immunorelated Pancytopenia

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yang Zhao ◽  
Yihao Wang ◽  
Hui Liu ◽  
Kai Ding ◽  
Chunyan Liu ◽  
...  
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Enzyme Linked Immunosorbent Assay ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr

Objectives. To explore effects of Epstein-Barr virus (EBV) infection on CD19+ B lymphocytes in patients with immunorelated pancytopenia (IRP). Methods. An enzyme-linked immunosorbent assay (ELISA) in vitro diagnostic kit was used to detect EBV capsid antigen- (CA-) IgG and VCA-IgM antibodies in the serum. We analyzed the EBV-DNA copies of CD19+ B lymphocyte by using real-time quantitative polymerase chain reaction (RT-qPCR). CD21, CD23, CD5, CD80, and CD86 receptors on the surfaces of CD19+ B cells were detected by flow cytometry (FCM). The correlation between these receptors and EBV-DNA copies were evaluated. Results. The results revealed that the positive rate of EBVCA-IgM and CD19+ B lymphocyte EBV-DNA copy in the IRP group were significantly higher than those in the control group (P<0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (P<0.05). Expression levels of the CD21, CD23, CD5, CD80, and CD86 receptors on the surfaces of CD19+ B cells in IRP patients with anti-EBVCA IgM positivity were significantly higher than those in anti-EBVCA IgM negativity IRP patients (P<0.05). The results revealed that EBV-DNA copy numbers were positively correlated with CD21, CD23, CD5, CD80, and CD86 expression. Conclusions. EBV infection may activate CD19+ B lymphocytes and further disrupt bone marrow hematopoiesis in IRP patients.

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

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1211 ◽  
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.

scholarly journals Transcribed B lymphocyte genes and multiple sclerosis risk genes are underrepresented in Epstein–Barr Virus hypomethylated regions

2019 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Lawrence T. C. Ong ◽  
Grant P. Parnell ◽  
Ali Afrasiabi ◽  
Graeme J. Stewart ◽  
Sanjay Swaminathan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
B Cells ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Sequencing Data ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Activated B Cells

Abstract Epstein–Barr Virus (EBV) infection appears to be necessary for the development of Multiple Sclerosis (MS), although the specific mechanisms are unknown. More than 200 single-nucleotide polymorphisms (SNPs) are known to be associated with the risk of developing MS. About a quarter of these are also highly associated with proximal gene expression in B cells infected with EBV (lymphoblastoid cell lines—LCLs). The DNA of LCLs is hypomethylated compared with both uninfected and activated B cells. Since methylation can affect gene expression, and so cell differentiation and immune evasion, we hypothesised that EBV-driven hypomethylation may affect the interaction between EBV infection and MS. We interrogated an existing dataset comprising three individuals with whole-genome bisulfite sequencing data from EBV transformed B cells and CD40L-activated B cells. DNA methylation surrounding MS risk SNPs associated with gene expression in LCLs (LCLeQTL) was less likely to be hypomethylated than randomly selected chromosomal regions. Differential methylation was independent of genomic features such as promoter regions, but genes preferentially expressed in EBV-infected B cells, including the LCLeQTL genes, were underrepresented in the hypomethylated regions. Our data does not indicate MS genetic risk is affected by EBV hypomethylation.

scholarly journals Epstein–Barr virus infection is associated with clinical characteristics and poor prognosis of multiple myeloma

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Bing Xia ◽  
Xi Wang ◽  
Ruifang Yang ◽  
Li Mengzhen ◽  
Kunpeng Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Characteristics ◽  
Epstein Barr Virus ◽  
High Expression ◽  
Epstein Barr Virus Infection ◽  
Dna Concentration ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr

Abstract The aim of the present study was to evaluate the relationship of Epstein–Barr virus (EBV) infection and multiple myeloma (MM) and its impact on clinical characteristics and prognosis. Fresh peripheral blood mononuclear cells (PBMCs) from 139 MM patients who had been diagnosed and treated from January 2010 to May 2018 and 50 PBMC samples from healthy donors were obtained. PCR was carried out for detection of EBV-DNA. The results indicated a significantly higher EBV-DNA concentration among 139 MM patients compared with healthy controls (P&lt;0.05). Correlation analysis showed that the expression of EBV-DNA was positively correlated with the serum free light chain ratio (sFLCR) and progressive disease (PD)/relapse (P&lt;0.05). Especially, in EBV-DNA high-expression MM patients, EBV-DNA concentration for patients with sFLCR ≥100 was higher than that of patients with sFLCR &lt;100. EBV-DNA concentration was higher in patients with disease PD/relapse than those without disease PD/relapse. In univariate analysis, the progress free survival (PFS) was inferior in MM patients with high expression of EBV-DNA, high lactate dehydrogenase (LDH), and high-risk according to mSMART and International Myeloma Working Group (IMWG), stage III according to R-ISS staging, extramedullary lesions, and genetic changes (P&lt;0.05). However, in multivariate analysis, LDH, poor karyotype, R-ISS staging, and mSMART were independent prognostic factors for PFS. Taken together, our studies suggest that an association exists between EBV infection and clinical characteristics of MM patients, and EBV infection appears to have a slight impact on the prognosis of MM. However, the results require further validation in other independent prospective MM cohorts.

scholarly journals β1 Integrin Expression Increases Susceptibility of Memory B Cells to Epstein-Barr Virus Infection

2010 ◽  
Vol 84 (13) ◽  
pp. 6667-6677 ◽  
Author(s):  
Marcus Dorner ◽  
Franziska Zucol ◽  
Davide Alessi ◽  
Stephan K. Haerle ◽  
Walter Bossart ◽  
...  
Keyword(s):  
B Cells ◽  
Epstein Barr Virus ◽  
Signal Transduction Pathway ◽  
Cell Receptor ◽  
Memory B Cells ◽  
Epstein Barr Virus Infection ◽  
Integrin Expression ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) uses nasal mucosa-associated lymphoid tissue (NALT) as a portal of entry to establish life-long persistence in memory B cells. We previously showed that naïve and memory B cells from NALT are equally susceptible to EBV infection. Here we show that memory B cells from NALT are significantly more susceptible to EBV infection than those from remote lymphatic organs. We identify β1 integrin, which is expressed the most by naïve B cells of distinct lymphoid origin and by memory B cells from NALT, as a mediator of increased susceptibility to infection by EBV. Furthermore, we show that BMRF-2-β1 integrin interaction and the downstream signal transduction pathway are critical for postbinding events. An increase of β1 integrin expression in peripheral blood memory B cells provoked by CD40 stimulation plus B-cell receptor cross-linking increased the susceptibility of non-NALT memory B cells to EBV infection. Thus, EBV seems to utilize the increased activation status of memory B cells residing in the NALT to establish and ensure persistence.

scholarly journals Latent Membrane Protein 2B Regulates Susceptibility to Induction of Lytic Epstein-Barr Virus Infection

2007 ◽  
Vol 82 (4) ◽  
pp. 1739-1747 ◽  
Author(s):  
Markus P. Rechsteiner ◽  
Christoph Berger ◽  
Ludwig Zauner ◽  
Jürg A. Sigrist ◽  
Matthias Weber ◽  
...  
Keyword(s):  
B Cells ◽  
Membrane Protein ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Cross Linking ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT The B-lymphotropic Epstein-Barr virus (EBV) encodes two isoforms of latent membrane protein 2 (LMP2), LMP2A and LMP2B, which are expressed during latency in B cells. The function of LMP2B is largely unknown, whereas LMP2A blocks B-cell receptor (BCR) signaling transduction and induction of lytic EBV infection, thereby promoting B-cell survival. Transfection experiments on LMP2B in EBV-negative B cells and the silencing of LMP2B in EBV-harboring Burkitt's lymphoma-derived Akata cells suggest that LMP2B interferes with the function of LMP2A, but the role of LMP2B in the presence of functional EBV has not been established. Here, LMP2B, LMP2A, or both were overexpressed in EBV-harboring Akata cells to study the function of LMP2B. The overexpression of LMP2B increased the magnitude of EBV switching from its latent to its lytic form upon BCR cross-linking, as indicated by a more-enhanced upregulation and expression of EBV lytic genes and significantly increased production of transforming EBV compared to Akata vector control cells or LMP2A-overexpressing cells. Moreover, LMP2B lowered the degree of BCR cross-linking required to induce lytic EBV infection. Finally, LMP2B colocalized with LMP2A as demonstrated by immunoprecipitation and immunofluorescence and restored calcium mobilization upon BCR cross-linking, a signaling process inhibited by LMP2A. Thus, our findings suggest that LMP2B negatively regulates the function of LMP2A in preventing the switch from latent to lytic EBV replication.

scholarly journals Epstein-Barr Virus Can Establish Infection in the Absence of a Classical Memory B-Cell Population

2005 ◽  
Vol 79 (17) ◽  
pp. 11128-11134 ◽  
Author(s):  
Margaret Conacher ◽  
Robin Callard ◽  
Karen McAulay ◽  
Helen Chapel ◽  
David Webster ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Population ◽  
Germinal Center ◽  
Epstein Barr Virus ◽  
Memory B Cell ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persists in the body for life after primary infection. The primary site of EBV persistence is the memory B lymphocyte, but whether the virus initially infects naïve or memory B cells is still disputed. We have analyzed EBV infection in nine cases of X-linked hyper-immunoglobulin M (hyper-IgM) syndrome who, due to a mutation in CD40 ligand gene, do not have a classical, class-switched memory B-cell population (IgD− CD27+). We found evidence of EBV infection in 67% of cases, which is similar to the infection rate found in the general United Kingdom population (60 to 70% for the relevant age range). We detected EBV DNA in peripheral blood B cells and showed in one case that the infection was restricted to the small population of nonclassical, germinal center-independent memory B cells (IgD+ CD27+). Detection of EBV small RNAs, latent membrane protein 2, and EBV nuclear antigen 3C expression in peripheral blood suggests full latent viral gene expression in this population. Analysis of EBV DNA in serial samples showed variability over time, suggesting cycles of infection and loss. Our results demonstrate that short-term EBV persistence can occur in the absence of a germinal center reaction and a classical memory B-cell population.

scholarly journals Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain

2007 ◽  
Vol 204 (12) ◽  
pp. 2899-2912 ◽  
Author(s):  
Barbara Serafini ◽  
Barbara Rosicarelli ◽  
Diego Franciotta ◽  
Roberta Magliozzi ◽  
Richard Reynolds ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Plasma Cells ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Postmortem Brain Tissue ◽  
Epstein Barr

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8+ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.

scholarly journals Epigenetic silencing of tumor suppressor genes during in vitro Epstein–Barr virus infection

2015 ◽  
Vol 112 (37) ◽  
pp. E5199-E5207 ◽  
Author(s):  
Abhik Saha ◽  
Hem C. Jha ◽  
Santosh K. Upadhyay ◽  
Erle S. Robertson
Keyword(s):  
Tumor Suppressor ◽  
B Lymphocytes ◽  
Epstein Barr Virus ◽  
Epigenetic Modifications ◽  
Regulatory Sequences ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Human Cancers ◽  
Epstein Barr

DNA-methylation at CpG islands is one of the prevalent epigenetic alterations regulating gene-expression patterns in mammalian cells. Hypo- or hypermethylation-mediated oncogene activation, or tumor suppressor gene (TSG) silencing mechanisms, widely contribute to the development of multiple human cancers. Furthermore, oncogenic viruses, including Epstein–Barr virus (EBV)-associated human cancers, were also shown to be influenced by epigenetic modifications on the viral and cellular genomes in the infected cells. We investigated EBV infection of resting B lymphocytes, which leads to continuously proliferating lymphoblastoid cell lines through examination of the expression pattern of a comprehensive panel of TSGs and the epigenetic modifications, particularly methylation of their regulatory sequences. EBV infection of primary B lymphocytes resulted in global transcriptional repression of TSGs through engagement of hypermethylation. Therefore, CpG methylation profiles of TSGs may be used as a prognostic marker as well as development of potential therapeutic strategies for controlling acute infection and EBV-associated B-cell lymphomas.

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

F1000Research ◽  
2019 ◽  
Vol 7 ◽  
pp. 1211
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 serum 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.

scholarly journals Uncovering Early Events in Primary Epstein-Barr Virus Infection Using a Rabbit Model

2021 ◽  
Author(s):  
Narendran Reguraman ◽  
Asma Hassani ◽  
Pretty Philip ◽  
Prof Gulfaraz Khan
Keyword(s):  
Animal Model ◽  
B Cells ◽  
Epstein Barr Virus ◽  
Rabbit Model ◽  
Epstein Barr Virus Infection ◽  
Ki 67 ◽  
Barr Virus ◽  
Ebv Infection ◽  
Infected Cells ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV) is an oncogenic herpesvirus implicated in the pathogenesis of several malignant and non-malignant conditions. However, a number of fundamental aspects of the biology of EBV and the mechanism(s) by which this virus induces pathology remain unknown. One major obstacle has been the lack of a suitable animal model for EBV infection. In this study, using our recently established rabbit model of EBV infection, we examined the early events following primary EBV infection. We show that, both immunocompetent and immunosuppressed animals were readily susceptible to EBV infection. However, immunosuppressed animals showed marked splenomegaly and widespread infection. Following EBV infection, the virus primarily targeted naïve IgM+, CD20+, CD21+ and CD79a+ B cells. Infected cells expressed varying sets of viral latent/lytic gene products. Notably, co-expression of latent and lytic proteins was not observed. Infected cells in type 0/1 latency (EBER+), were small and proliferating (Ki67+). By contrast, cells in type 2/3 latency (LMP1+), were large, non-proliferating (Ki-67−) and p53+. Although infected B-cells were widely present in splenic follicles, they did not express germinal center marker, BCL-6. Taken together, this study shows for the first time, some of the early events following primary EBV infection in an animal model.

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