scholarly journals Epstein–Barr Virus Reactivation-Induced Immunoglobulin Production: Significance on Autoimmunity

2020 ◽  
Vol 8 (12) ◽  
pp. 1875
Author(s):  
Keiko Nagata ◽  
Kazuhiko Hayashi
Keyword(s):  
B Cells ◽  
Autoimmune Diseases ◽  
Production System ◽  
Epstein Barr Virus ◽  
Plasma Cells ◽  
Virus Reactivation ◽  
Autoreactive B Cells ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

Epstein–Barr virus (EBV) mainly persists in B cells, which differentiate into antibody-producing cells, and thus, EBV has been implicated in autoimmune diseases. We aimed to describe the EBV reactivation and its relevance to autoimmune disease, focusing on Graves’ disease, which is an autoimmune hyperthyroidism caused by thyrotropin receptor antibodies. Circulating autoreactive B cells that have evaded from the selection have difficulties differentiating to produce antibodies. However, once EBV infects such B cells and reactivates, the B cells may become plasma cells and produce autoantibody. We herein proposed an EBV reactivation-induced Ig production system, which is a distinct pathway from the antibody production system through germinal centers and bone marrow and has the following characteristics: 1. IgM dominance, 2. ubiquitous Ig production, and 3. the rescue of autoreactive B cells, which skews Ig production toward autoantigens. IgM autoantibodies induced by EBV reactivation may activate the classical complement pathway and injure healthy tissue, which supply autoantigens for the production of affinity-matured IgG autoantibodies. Antibodies induced by EBV reactivation may play important roles in the development and exacerbation of autoimmune diseases.

scholarly journals Differential Expression of the miR-200 Family MicroRNAs in Epithelial and B Cells and Regulation of Epstein-Barr Virus Reactivation by the miR-200 Family Member miR-429

2010 ◽  
Vol 84 (15) ◽  
pp. 7892-7897 ◽  
Author(s):  
Zhen Lin ◽  
Xia Wang ◽  
Claire Fewell ◽  
Jennifer Cameron ◽  
Qinyan Yin ◽  
...  
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Family Member ◽  
Epstein Barr Virus ◽  
Family Members ◽  
Receptor Activation ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

ABSTRACT The miR-200 microRNA family is important for maintaining the epithelial phenotype, partially through suppressing ZEB1 and ZEB2. Since ZEB1 inhibits Epstein-Barr virus (EBV) reactivation, we hypothesized that expression of miR-200 family members in epithelial cells may partly account for higher levels of EBV reactivation in this tissue (relative to nonplasma B cells). Here we show that, whereas miR-200 family members are expressed in epithelial cells, their expression is low in latently infected B cells. Furthermore, the miR-200 family member miR-429 shows elevated expression in plasma cell lines and is induced by B-cell-receptor activation in Akata cells. Lastly, expression of miR-429 can break latency.

scholarly journals Cytolytic Epstein-Barr Virus Reactivation Therapy for EBV-Associated Gastric Carcinoma

2020 ◽  
pp. 1-10
Author(s):  
Jaap M. Middeldorp ◽  
Zlata Novalić ◽  
Sandra A.W.M. Verkuijlen ◽  
Astrid E. Greijer ◽  
Jaap M. Middeldorp
Keyword(s):  
Gastric Carcinoma ◽  
Mouse Model ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Drug Combinations ◽  
Model Systems ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

Background: Epstein-Barr virus associated gastric carcinoma (EBVaGC) is considered a distinct GC disease entity, with the virus persisting in a latent phase. Treatment with Epirubicin, Capecitabine and Cisplatin (ECC combination) showed survival benefit in patients with GC in clinical trials (MAGIC study and CRITICS study) when compared to chemotherapy with Capecitabine and Cisplatin (GCb/Cis). Current treatment protocols for GC do not consider virus involvement. Methods: In this study, we tested a CytoLytic Virus Activation (CLVA) strategy consisting of the ECC combination or GCb/Cis together with the HDAC inhibitor Valproic acid (VPA) to define whether EBV reactivation and subsequent antiviral treatment with Ganciclovir (GCV) could be used as virus-targeted therapy for EBVaGC. Drug combinations with VPA and GCV were evaluated in multiple cell lines and in an EBVaGC mouse model based on human naturally EBV-infected SNU-719 cells. Results: EBV reactivation was demonstrated by lytic mRNA transcripts and proteins in treated cells, and the virus-reactivating capacity of different CLVA drug combinations was compared in C666.1, AGS-BX1 and SNU-719 cell lines. In an EBVaGC mouse model, GCb/Cis with VPA and GCV strongly reduced tumor volume and showed the highest potential for EBV-reactivation. Upon a single round of CLVA treatment, EBV DNA levels in circulation decreased, and loss of EBV-positive cells in treated tumors was observed. In vivo EBV-reactivation was revealed by the presence of lytic gene transcripts and proteins in tumor tissues 6 days after treatment. Conclusion: In EBVaGC model systems, CLVA treatment showed a more potent virus reactivation and killing of tumor cells when compared to standard chemotherapy alone, suggesting that addition of VPA plus GCV to the ECC or GCb/Cis combination should be considered in future clinical studies.

scholarly journals Clinical characteristics and outcomes of critically ill patients with acute COVID-19 with Epstein-Barr virus reactivation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yun Xie ◽  
Song Cao ◽  
Hui Dong ◽  
Hui Lv ◽  
Xiaolei Teng ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Mortality Rates ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Imaging Characteristics ◽  
Single Center Study ◽  
Significant Difference ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

Abstract Background Our goal is to further elucidate the clinical condition and prognosis of patients with severe acute COVID-19 with EBV reactivation. Method This is a retrospective single-center study of COVID-19 patients admitted to the intensive care unit of Wuhan No. 3 Hospital (January 31 to March 27, 2020). According to whether Epstein-Barr virus reactivation was detected, the patients were divided into an EBV group and a Non-EBV group. Baseline data were collected including epidemiological, larithmics, clinical and imaging characteristics, and laboratory examination data. Results Of the 128 patients with COVID-19, 17 (13.3%) were infected with Epstein-Barr virus reactivation. In the symptoms,the rate of tachypnoea in the EBV group was apparently higher than that in the Non-EBV group. In lab tests, the lymphocyte and albumin of EBV group decreased more significantly than Non-EBV group, and the D-dimer and serum calcium of EBV group was higher than Non-EBV group. Regarding the infection index, CRP of EBV group was apparently above the Non-EBV group, and no significant difference was found in procalcitonin of the two groups. The incidence of respiratory failure, ARDS, and hypoproteinaemia of EBV group had more incidence than Non-EBV group. The 28-day and 14-day mortality rates of EBV group was significantly higher than that of Non-EBV group. Conclusions In the COVID-19 patients, patients with EBV reactivation had higher 28-day and 14-day mortality rates and received more immuno-supportive treatment than patients of Non-EBV group.

scholarly journals An Absence of Epstein–Barr Virus Reactivation and Associations with Disease Activity in People with Multiple Sclerosis Undergoing Therapeutic Hookworm Vaccination

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 487
Author(s):  
Peter A. C. Maple ◽  
Bruno Gran ◽  
Radu Tanasescu ◽  
David I. Pritchard ◽  
Cris S. Constantinescu
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Virus Reactivation ◽  
Serum Samples ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Reactivation ◽  
Epstein Barr

Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship with disease activity in people with MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1) IgG, and EBV early antigen (EA) IgG. Disease activity was assessed by periodic MRI. Significance was set at p < 0.05. Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2% were EBV EA IgG positive. EBV antibody levels were generally stable, and EBV reactivation in PwMS was not demonstrated by significant increases in IgG titre over 12 months. Disease activity was most frequent in PwMS possessing high levels of EBV VCA IgG (>600 units/mL) or EBNA-1 IgG (>150 units/mL); however, there was no association with hookworm treatment. Interpretation: Therapeutic hookworm vaccination was not associated with EBV reactivation. Multiple sclerosis disease activity was associated with high levels of EBV VCA IgG or EBNA-1 IgG.

Inhibition of Cell Growth and Epstein-Barr Virus Reactivation by CD40 Stimulation in Epstein-Barr Virus-Transformed B Cells

2000 ◽  
Vol 13 (2) ◽  
pp. 215-229 ◽  
Author(s):  
MAKOTO FUKUDA ◽  
TOMOHIS A. SATOH ◽  
MASAKATU TAKANASHI ◽  
KANJI HIRAI ◽  
EIKO OHNISHI ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Growth ◽  
Epstein Barr Virus ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Cd40 Stimulation ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

scholarly journals Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis

2020 ◽  
Vol 117 (25) ◽  
pp. 14421-14432
Author(s):  
Thomas Sommermann ◽  
Tomoharu Yasuda ◽  
Jonathan Ronen ◽  
Tristan Wirtz ◽  
Timm Weber ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Plasma Cells ◽  
Cell Transformation ◽  
Barr Virus ◽  
Nuclear Antigens ◽  
Epstein Barr ◽  
Cell Transforming ◽  
Early B Cell Factor

Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphomagenesis.

scholarly journals Essential role of PKCδ in histone deacetylase inhibitor-induced Epstein–Barr virus reactivation in nasopharyngeal carcinoma cells

2008 ◽  
Vol 89 (4) ◽  
pp. 878-883 ◽  
Author(s):  
Heng-Huan Lee ◽  
Shih-Shin Chang ◽  
Sue-Jane Lin ◽  
Huey-Huey Chua ◽  
Tze-Jiun Tsai ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Epstein Barr Virus ◽  
Nuclear Translocation ◽  
Chemotherapeutic Agents ◽  
Lytic Cycle ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Deacetylase Inhibitor ◽  
Epstein Barr

Histone deactylase inhibitors (HDACi) are common chemotherapeutic agents that stimulate Epstein–Barr virus (EBV) reactivation; the detailed mechanism remains obscure. In this study, it is demonstrated that PKCδ is required for induction of the EBV lytic cycle by HDACi. Inhibition of PKCδ abrogates HDACi-mediated transcriptional activation of the Zta promoter and downstream lytic gene expression. Nuclear translocation of PKCδ is observed following HDACi stimulation and its overexpression leads to progression of the EBV lytic cycle. Our study suggests that PKCδ is a crucial mediator of EBV reactivation and provides a novel insight to study the regulation of the EBV lytic cycle.

scholarly journals Epstein-Barr Virus LMP2A Enhances B-Cell Responses In Vivo and In Vitro

2006 ◽  
Vol 80 (14) ◽  
pp. 6764-6770 ◽  
Author(s):  
Michelle Swanson-Mungerson ◽  
Rebecca Bultema ◽  
Richard Longnecker
Keyword(s):  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Plasma Cells ◽  
Barr Virus ◽  
Epstein Barr ◽  
Hen Egg ◽  
Hen Egg Lysozyme

ABSTRACT Epstein-Barr virus (EBV) establishes latent infections in a significant percentage of the population. Latent membrane protein 2A (LMP2A) is an EBV protein expressed during latency that inhibits B-cell receptor signaling in lymphoblastoid cell lines. In the present study, we have utilized a transgenic mouse system in which LMP2A is expressed in B cells that are specific for hen egg lysozyme (E/HEL-Tg). To determine if LMP2A allows B cells to respond to antigen, E/HEL-Tg mice were immunized with hen egg lysozyme. E/HEL-Tg mice produced antibody in response to antigen, indicating that LMP2A allows B cells to respond to antigen. In addition, E/HEL-Tg mice produced more antibody and an increased percentage of plasma cells after immunization compared to HEL-Tg littermates, suggesting that LMP2A increased the antibody response in vivo. Finally, in vitro studies determined that LMP2A acts directly on the B cell to increase antibody production by augmenting the expansion and survival of the activated B cells, as well as increasing the percentage of plasma cells generated. Taken together, these data suggest that LMP2A enhances, not diminishes, B-cell-specific antibody responses in vivo and in vitro in the E/HEL-Tg system.

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.

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