Roles of Inflammasomes in Epstein–Barr Virus-Associated Nasopharyngeal Cancer

Epstein–Barr virus (EBV) infection is recognised as one of the causative agents in most nasopharyngeal carcinoma (NPC) cases. Expression of EBV viral antigens can induce host’s antiviral immune response by activating the inflammasomes to produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. These cytokines are known to be detrimental to a wide range of virus-infected cells, in which they can activate an inflammatory cell death program, called pyroptosis. However, aberrant inflammasome activation and production of its downstream cytokines lead to chronic inflammation that may contribute to various diseases, including NPC. In this review, we summarise the roles of inflammasomes during viral infection, how EBV evades inflammasome-mediated immune response, and progress into tumourigenesis. The contrasting roles of inflammasomes in cancer, as well as the current therapeutic approaches used in targeting inflammasomes, are also discussed in this review. While the inflammasomes appear to have dual roles in carcinogenesis, there are still many questions that remain unanswered. In particular, the exact molecular mechanism responsible for the regulation of the inflammasomes during carcinogenesis of EBV-associated NPC has not been explored thoroughly. Furthermore, the current practical application of inflammasome inhibitors is limited to specific tumour types, hence, further studies are warranted to discover the potential of targeting the inflammasomes for the treatment of NPC.

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Faculty Opinions recommendation of Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.728367175.793536815 ◽

2017 ◽

Author(s):

Marc S Williams

Keyword(s):

Epstein Barr Virus ◽

Nasopharyngeal Cancer ◽

Barr Virus ◽

Epstein Barr

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

Microbiology Research ◽

10.3390/microbiolres12010011 ◽

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.

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Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis

Medical Hypotheses ◽

10.1016/j.mehy.2007.04.030 ◽

2008 ◽

Vol 70 (1) ◽

pp. 66-69 ◽

Cited By ~ 43

Author(s):

Trygve Holmøy

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Vitamin D ◽

Immune Response ◽

Synergistic Effect ◽

Epstein Barr Virus ◽

Vitamin D Status ◽

Barr Virus ◽

Epstein Barr

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Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Journal of Innate Immunity ◽

10.1159/000479749 ◽

2017 ◽

Vol 9 (6) ◽

pp. 574-586 ◽

Cited By ~ 33

Author(s):

Yuanjun Lu ◽

Zailong Qin ◽

Jia Wang ◽

Xiang Zheng ◽

Jianhong Lu ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Epstein Barr Virus ◽

Type I ◽

Receptor Signaling ◽

Viral Pathogen ◽

Infection Period ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr

Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3′UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance.

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THE VALUE OF THE IMMUNE RESPONSE IN PATIENTS WITH EBV INFECTIOUS MONONUCLEOSIS IN PREDICTING THE COURSE AND EFFICACY OF ANTIVIRAL AND IMMUNO IMMUNOCORRECTING THERAPY

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40689 ◽

2013 ◽

Vol 18 (1) ◽

pp. 7-14

Author(s):

T. A. Svintsova ◽

D. M. Sobchak ◽

O. V. Korochkina ◽

G. A Kravchenko ◽

V. V Novikov

Keyword(s):

Immune Response ◽

Infectious Mononucleosis ◽

Epstein Barr Virus ◽

Mononuclear Cells ◽

Polyclonal Antibodies ◽

Severity Of Illness ◽

Control Group ◽

Differentiation Antigens ◽

Barr Virus ◽

Epstein Barr

The indices of immune response were studied in 68 patients with infectious mononucleosis caused by the Epstein-Barr virus (35 males, 33 females) aged 18 to 30 years. Materials and methods. The content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50, sHLAI, sCD54) has been studied with enzyme immunoassay using monoclonal antibodies Mab IC0-20 and polyclonal antibodies to the antigens of the mononuclear cells of the peripheral blood. The control group included 60 healthy volunteers matched for age and sex with the main group. The aim of this study is the assessment of the content of soluble forms of differentiation antigens in patients with infectious mononucleosis caused by Epstein-Barr virus, depending on gender, age, severity of illness, comorbidities, laboratory values, the presence of viral DNA, as well as a demonstration of their value in predicting the course and outcome of the disease and the efficacy of antiviral and immunocorrecting therapy. In patients with negative results of DNA indication of EBV a significant increase in the content of soluble forms of differentiation antigens characterizing the adhesion of leukocytes (sCD18), the activity of T-lymphocytes (sCD50), the recognition of foreign antigens (sHLAI) in the blood in comparison with patients with a positive DNA indication of EBV was determined. Conclusion. According to the results of this performed work the criterion for an adequate immune response in patients with infectious mononucleosis caused by the Epstein-Barr virus was found to be the increase of the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54). In patients with exanthema, tonsillar syndrome, leukocytosis, elevation of transaminases and the presence of antibodies to capsid antigen (a/VCAIgM) the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54), was higher than in patients without such symptoms. In the treatment with cycloferon in patients with cyclic course of EBV infectious mononucleosis the content of sHLAI and sCD54 at 2nd-4th weeks of treatment increased by 1.5-2 times compared with the corresponding values before treatment. In patients with reactivation of the disease monotonically low indices of all studied soluble forms of differentiation antigens persisted over the 4 weeks during patients following up. In patients with infectious mononucleosis caused by Epstein-Barr virus, the dynamics of sHLAI and sCD54 after 2-4 weeks of treatment serves as secondary efficacy endpoint of antiviral, immunomodulatory therapy and the formation of the cyclic course of the disease.

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Prevalence of Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Subclinical Infection in Patients with Acute Immune Thrombocytopenic Purpura (ITP)

International Journal of Hematology-Oncology and Stem Cell Research ◽

10.18502/ijhoscr.v15i3.6843 ◽

2021 ◽

Author(s):

Farshad Abbasi ◽

Gholam Abbas Kaydani ◽

Zari Tahannezhad ◽

Mohsen Nakhaie ◽

Ali Amin Asnafi ◽

...

Keyword(s):

Immune Thrombocytopenic Purpura ◽

Epstein Barr Virus ◽

Blood Platelets ◽

Control Group ◽

Thrombocytopenic Purpura ◽

Barr Virus ◽

Causative Agents ◽

Exact Etiology ◽

Epstein Barr ◽

Acute Itp

Background: Immune thrombocytopenic purpura (ITP) defined as a bleeding disorder in which the number and production of platelets reduced by the immune system; however, the destruction of peripheral blood platelets also occurs. Although its exact etiology and pathogenesis not already know, several studies have shown that Epstein-Barr virus (EBV) and cytomegalovirus (CMV) known as possible causative agents of ITP. This investigation aims to evaluate the presence of CMV and EBV in two groups of case and control by polymerase chain reaction (PCR). Materials and Methods: We considered the presence of CMV and EBV in 48 acute ITP patients and 48 healthy people. Study participants were recruited from Ahvaz Shafa Hospital between 2017 and 2018 and the presence of two viruses was investigated by (PCR). Results: Out of 48 acute ITP patients, the CMV DNA was detected from the blood of 12 (25%) patients and the EBV DNA from the blood of 2 (4.2%) other patients. In addition, only one patient was (2.1%) co-infected with CMV and EBV. In contrast, in 48 healthy subjects, 3 (6.6%) had CMV and none of the control group was infected with EBV. Conclusion: Due to the presence of both EBV and CMV in the acute ITP patients in Ahvaz, they can be considered as factors in the progression of this disease. Therefore, consideration of the methods of elimination and treatment of these two viruses in these patients may be used as a treatment strategy in ITP patients in the future.

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Acyclovir Improves the Efficacy of Chemoradiation in Nasopharyngeal Cancer Containing the Epstein Barr Virus Genome

10.1101/2020.10.18.343236 ◽

2020 ◽

Author(s):

Aditya Thandoni ◽

Andrew Zloza ◽

Devora Schiff ◽

Malay Rao ◽

Kwok-wai Lo ◽

...

Keyword(s):

Epstein Barr Virus ◽

Treatment Options ◽

Immune Surveillance ◽

Nasopharyngeal Cancer ◽

Standard Of Care ◽

Virus Genome ◽

Barr Virus ◽

Standard Of Care Treatment ◽

Epstein Barr

AbstractNasopharyngeal carcinoma (NPC) is a malignancy endemic to East Asia and is caused by Epstein-Barr Virus (EBV)-mediated cancerous transformation of epithelial cells. The standard of care treatment for NPC involves radiation and chemotherapy. While treatment outcomes continue to improve, up to 50% of patients can be expected to recur by five years, and additional innovative treatment options are needed. We posit that a potential way to do this is by targeting the underlying cause of malignant transformation, namely EBV. One method by which EBV escapes immune surveillance is by undergoing latent phase replication, during which EBV expression of immunogenic proteins is reduced. However, chemoradiation is known to drive conversion of EBV from a latent to a lytic phase. This creates an opportunity for the targeting of EBV-infected cells utilizing anti-viral drugs. Indeed, we found that combining acyclovir with cisplatin and radiation significantly decreases the viability of the EBV-infected C666-1 cell line. Western blot quantification revealed a resultant increase of thymidine kinase (TK) and apoptosis-inducing mediators, cleaved PARP (cPARP) and phosphorylated ERK (pERK). These studies suggest that the addition of anti-viral drugs to frontline chemoradiation may improve outcomes in patients treated for EBV-related NPC and future in vivo and clinical studies are needed.

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Conserved Peptide with Therapeutic Potential to Overcome Nasopharyngeal Carcinoma

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v13i1.490 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Muhaimin R ◽

Widyarti S ◽

Widodo N

Keyword(s):

B Cells ◽

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Therapeutic Potential ◽

Nasopharyngeal Cancer ◽

Passive Immunization ◽

Spleen Cells ◽

Specific Antibodies ◽

Barr Virus ◽

Epstein Barr

Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma that arises in the upper lining epithelium of the nasopharynx. In this study, conserved peptide (Ulin-1) of Epstein-Barr virus constructed by Biomodelling and Biocomputation was tested for its ability to stimulate B cells to produce specific antibodies. Spleen cells were isolated and cultured with anti-CD3 and lipopolysaccharide (LPS), and treated or not treated with Ulin-1. Cell culture was harvested six days after incubation and analyzed by flow cytometry. Here, we demonstrated the ability of Ulin-1 to stimulate B cells to produce specific antibodies. The results of this study illustrate the importance of Ulin-1 engineered by Biomodelling and Biocomputation as both active and passive immunization agents against nasopharyngeal cancer.

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