scholarly journals The Microenvironment in Epstein–Barr Virus-Associated Malignancies

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 40 ◽  
Author(s):  
Geok Tan ◽  
Lydia Visser ◽  
Lu Tan ◽  
Anke Berg ◽  
Arjan Diepstra
Keyword(s):  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Immune Escape ◽  
Cell Types ◽  
Barr Virus ◽  
Adaptive Immune Cells ◽  
Associated Malignancy ◽  
Epstein Barr ◽  
Immune Escape Mechanisms ◽  
Different Cell Types

The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an aspecific reaction to the tumor cells. In fact, latent EBV-infected tumor cells utilize several specific mechanisms to form and shape the TME to their own benefit. These mechanisms have been studied largely in the context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and EBV+ gastric cancer. This review describes the composition, immune escape mechanisms, and tumor cell promoting properties of the TME in these three malignancies. Mechanisms of susceptibility which regularly involve genes related to immune system function are also discussed, as only a small proportion of EBV-infected individuals develops an EBV-associated malignancy.

scholarly journals Epstein-Barr Virus in Systemic Autoimmune Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anette Holck Draborg ◽  
Karen Duus ◽  
Gunnar Houen
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Immune Escape ◽  
Connective Tissue Diseases ◽  
Systemic Autoimmune Diseases ◽  
Barr Virus ◽  
Epstein Barr ◽  
Genetic And Environmental Factors ◽  
Immune Escape Mechanisms

Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

scholarly journals Viral Infection and Autophagy Dysregulation: The Case of HHV-6, EBV and KSHV

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2624
Author(s):  
Maria Anele Romeo ◽  
Roberta Santarelli ◽  
Maria Saveria Gilardini Montani ◽  
Roberta Gonnella ◽  
Rossella Benedetti ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Herpes Virus ◽  
Kaposi Sarcoma ◽  
Cell Types ◽  
Barr Virus ◽  
Human Herpes Virus ◽  
Autophagic Process ◽  
Epstein Barr ◽  
Herpès Virus ◽  
Different Cell Types

Human Herpes Virus-6 (HHV-6), Epstein-Barr Virus (EBV) and Kaposi Sarcoma Herpes Virus (KSHV) are viruses that share with other member of the Herpesvirus family the capacity to interfere with the autophagic process. In this paper, mainly based on the findings of our laboratory, we describe how, through different mechanisms, these viruses converge in reducing autophagy to impair DC immune function and how, by infecting and dysregulating autophagy in different cell types, they promote the pathologies associated with their infection, from the neurodegenerative diseases such Alzheimer’s disease to cancer.

scholarly journals Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer

2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Viral Load ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Tumor Volume ◽  
Nasopharyngeal Cancer ◽  
Dna Quantification ◽  
Barr Virus ◽  
Nasopharyngeal Biopsy ◽  
Ebv Dna ◽  
Epstein Barr

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

scholarly journals Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells

2017 ◽  
Vol 241 ◽  
pp. 24-33 ◽  
Author(s):  
A.E. Greijer ◽  
O. Ramayanti ◽  
S.A.W.M. Verkuijlen ◽  
Z. Novalić ◽  
H. Juwana ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Rna Profiling ◽  
Barr Virus ◽  
Epstein Barr ◽  
Target Rna ◽  
Infected Tumor

scholarly journals Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes for the Treatment of Patients With EBV-Positive Relapsed Hodgkin's Disease

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2925-2934 ◽  
Author(s):  
Marie A. Roskrow ◽  
Nobuhiro Suzuki ◽  
Yan-jun Gan ◽  
John W. Sixbey ◽  
Catherine Y.C. Ng ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Barr Virus ◽  
Specific Ctls ◽  
Epstein Barr ◽  
Relapsed Disease

Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) is effective prophylaxis and treatment of EBV-positive immunoblastic lymphoma in immunocompromised patients. In 50% of patients with Hodgkin's disease, the tumor cells are EBV antigen-positive and may therefore also be suitable targets for treatment with virus-specific CTLs. However, Hodgkin's disease may produce several inhibitory effects on immune induction and effector function in vivo, which may preclude the generation or effector function of CTLs reactive against EBV viral proteins, including those expressed by the tumor cells. We have investigated whether EBV-specific CTLs could be generated ex vivo from 13 patients with Hodgkin's disease: nine with active relapsed disease and four who were in clinical remission after a first or subsequent relapse. CTL lines were successfully generated from nine of 13 patients (five active disease, four remission). Although these lines had an abnormal pattern of expansion comparable to EBV-specific CTLs generated from normal donors, their phenotype was normal except for reduced expression of the zeta chain of the T-cell receptor (TCR). Their cytotoxicity was also compared to EBV-specific lines generated from normal donors and included activity against LMP2a, one of the three weakly immunogenic viral antigens expressed by Hodgkin's tumor cells. To assess the activity of the CTLs in vivo, they were gene-marked and infused into three patients with multiply relapsed disease. The CTLs persisted for more than 13 weeks postinfusion and retained their potent antiviral effects in vivo, thereby enhancing the patient immune response to EBV. This approach may therefore have value in the treatment of EBV-positive Hodgkin's disease.

scholarly journals Determination of Epstein-Barr Virus–Infected Lymphocyte Cell Types in Peripheral Blood Mononuclear Cells as a Valuable Diagnostic Tool in Hematological Diseases

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Peiling Zhang ◽  
Chen Zeng ◽  
Jiali Cheng ◽  
Jing Zhou ◽  
Jia Gu ◽  
...  
Keyword(s):  
Infected Cell ◽  
B Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Cell Types ◽  
Cell Type ◽  
Peripheral Blood Mononuclear ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background High loads of Epstein-Barr virus (EBV) in peripheral blood mononuclear cells (PBMCs) can be indicative of a broad spectrum of diseases, ranging from asymptomatic infection to fatal cancers. Methods We retrospectively investigated the EBV-infected cell types in PBMCs among 291 patients. Based on EBV-infected cell types, the clinical features and prognoses of 93 patients with EBV-associated (EBV+) T/natural killer (NK)–cell lymphoproliferative diseases (LPDs) T/NK-LPDs) were investigated over a 5-year period. Results Although B-cell-type infection was found in immunocompromised patients and patients with asymptomatic high EBV carriage, infectious mononucleosis, EBV+ B-cell LPDs and B-cell lymphomas, T-cell, NK-cell or multiple-cell-type infection in immunocompetent hosts were highly suggestive of EBV+ T/NK-LPDs, EBV+ T/NK-cell lymphomas, and aggressive NK-cell leukemia. Patients with non–B-cell infection had a poorer prognosis than those with B-cell-type infection. In our cohort, 79.6% of patients with EBV+ T/NK-LPDs were >18 years old, and NK cells were identified as EBV-infected cell type in 54.8%. Nearly half of patients with EBV+ T/NK-LPDs had genetic defects associated with immunodeficiency. However, hemophagocytic lymphohistiocytosis, and not genetic defects, was the only parameter correlated with poor prognosis of EBV+ T/NK-LPDs. Conclusions Determination of EBV-infected cell types among PBMCs is a valuable tool for the differential diagnosis of EBV+ hematological diseases. In this study, determination of Epstein-Barr virus-infected cell types in peripheral blood mononuclear cells of 291 patients with high Epstein-Barr virus loads were retrospectively investigated, which indicate it is a valuable tool for Epstein-Barr virus-associated hematological diseases.

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