scholarly journals Elevated Levels of Interferon-γ Are Associated with High Levels of Epstein-Barr Virus Reactivation in Patients with the Intestinal Type of Gastric Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
María G. Cárdenas-Mondragón ◽  
Javier Torres ◽  
Norma Sánchez-Zauco ◽  
Alejandro Gómez-Delgado ◽  
Margarita Camorlinga-Ponce ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Inflammatory Response ◽  
Virulence Factor ◽  
Epstein Barr Virus ◽  
Elevated Serum ◽  
Intestinal Type ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

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.

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.

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

Tumor Biology ◽  
2017 ◽  
Vol 39 (7) ◽  
pp. 101042831771771 ◽  
Author(s):  
Athira Nandakumar ◽  
Futoshi Uwatoko ◽  
Megumi Yamamoto ◽  
Kazuo Tomita ◽  
Hideyuki J Majima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Epstein Barr Virus ◽  
Virus Reactivation ◽  
Gastric Cancer Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Radiation Induced ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

scholarly journals Interferon-alpha-2a as a salvage treatment for hemorrhagic enteritis associated with Epstein-Barr Virus reactivation : a case report

2021 ◽  
Vol 84 (1) ◽  
pp. 129-130
Author(s):  
D Lankenau-Vela ◽  
F De la Garza-Salazar ◽  
P Colunga-Pedraza ◽  
D Jaime-Villalón
Keyword(s):  
Interferon Alpha ◽  
Epstein Barr Virus ◽  
Salvage Treatment ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Immunosuppressed Patients ◽  
Hemorrhagic Enteritis ◽  
Epstein Barr ◽  
Almost All

Epstein-Barr virus [EBV] is a virus that infects almost all humans worldwide. After the acute phase of the infection, it stays in a latent form in B lymphocytes. EBV reactivation tends to occur in immunosuppressed patients. EBV reactivation may involve the gastrointestinal tract ; it has been associated mainly with colitis, but hemorrhagic enteritis has been poorly reported. Treatment usually includes antivirals. However, our patient did not respond to conventional treatment, so interferon alpha-2a was given as a salvage treatment. To our knowledge, this is the first reported case of hemorrhagic enteritis associated to EBV reactivation treated successfully with interferon alpha-2a.

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 Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 763
Author(s):  
Jeffrey E. Gold ◽  
Ramazan A. Okyay ◽  
Warren E. Licht ◽  
David J. Hurley
Keyword(s):  
Epstein Barr Virus ◽  
Direct Result ◽  
Primary Study ◽  
Virus Reactivation ◽  
Exact Test ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr ◽  
The Difference

Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.

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