Role Of Epstein-Barr Virus Research Articles

MiRNA-218 Is Frequently Downregulated in Malignant Breast Tumors: A Footprint of Epstein-Barr Virus Infection

Background & Objective: The role of Epstein-Barr Virus in development of breast cancer is frequently studied. In this regard, miRNAs are among the contributing elements in the molecular pathophysiology of EBV-related diseases. In addition, a growing number of host miRNAs are believed to be implicated in pathogenesis of breast cancer. MiR-218 is a tumor suppressive miRNA that is subjected to dysregulation in various EBV-associated cancers. We aimed to investigate the frequency of EBV and its relationship with expression status of tumor suppressive miR-218 in breast cancer and adjacent normal tissue.Methods: A total number of 51 fresh malignant breast cancer tissues (cases) and their adjacent normal tissues (controls) were collected. Nested-PCR and RT-qPCR were set to identify EBV frequency and miR-218 expression in cases and controls, respectively.Results: Out of all samples, 6.8% (7/102) comprising 11.6% (6/51) in malignant tissues and 1.9% (1/51) in normal control tissues were positive for EBV (P<0.05). Quantitative data showed that miR-218 was significantly downregulated in malignant tissues compared to control tissues (P<0.0001). In addition, reduced expression of miR-218 was associated with adverse clinical outcomes, metastasis, and higher grades of malignancy. Given the presence of EBV, lower expression of miR-218 was observed in breast cancer group in comparison with normal group (P<0.05). Conclusion: Our results raise the possibility of the relation between EBV infection and miR-218 downregulation in breast cancer and propose further investigations in this regard.

Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cells.

Epstein-Barr virus (EBV) infection is associated with rheumatoid arthritis (RA) in adults, though the nature of the relationship remains unknown. Herein, we have examined the contribution of viral infection to the severity of arthritis in mice. We have provided the first evidence that latent gammaherpesvirus infection enhances clinical arthritis, modeling EBV's role in RA. Mice latently infected with a murine analog of EBV, gammaherpesvirus 68 (γHV68), develop more severe collagen-induced arthritis and a Th1-skewed immune profile reminiscent of human disease. We demonstrate that disease enhancement requires viral latency and is not due to active virus stimulation of the immune response. Age-associated B cells (ABCs) are associated with several human autoimmune diseases, including arthritis, though their contribution to disease is not well understood. Using ABC knockout mice, we have provided the first evidence that ABCs are mechanistically required for viral enhancement of disease, thereby establishing that ABCs are impacted by latent gammaherpesvirus infection and provoke arthritis.

Determination and Role of Epstein-Barr Virus in Patients With Lymphoproliferative Disorders

IntroductionEpstein-Barr virus (EBV) is associated with different types of human malignancies, including Burkitt lymphoma, nasopharyngeal carcinoma, and lymphomas. We retrospectively investigated the presence of EBV-DNA by real-time PCR in clinical samples of patients diagnosed as having hematologic malignancies while investigating the cause of lymphoproliferative disorders, and investigated its relationship to clinical manifestations. Patients and MethodsFifty clinical samples sent to Gazi University’s hematology clinics between November 2013 and March 2018 were included. EBV-DNA was investigated by real-time PCR method, and EBV-IgM and EBV-IgG antibodies were investigated by ELISA. ResultsFifty serum samples were investigated, and 10% (5/50) EBV-DNA positivity was determined in patients. Of the 5 patients with EBV-DNA positivity, 2 had acute lymphoblastic leukemia, 1 lymphoma, 1 T-cell lymphoma, and 1 B-cell lymphoma. Concomitant EBV-DNA and viral capsid antigen (VCA)-IgM positivity was not detected. The VCA-lgM test results of the all EBV-DNA–positive patients were negative and VCA-IgG positive (except for 1 patient). Regarding virus load, of the 5 samples, 2, 1, 1, and 1 of the samples had a virus load of 102, 103, 104, and 105 copies/mL, respectively. ConclusionEBV infection is threatening in patients with hematologic malignancies and are diagnosed by serologic and molecular methods. As a result of the study, we suggest that the detection of EBV-DNA by real-time PCR in patients being admitted with lymphoproliferative diseases and diagnosed as acute lymphoblastic leukemia and lymphomas may be useful in follow-up and treatment.

MiRNA-218 Is Frequently Downregulated in Malignant Breast Tumors: A Footprint of Epstein-Barr Virus Infection.

Background & Objective:The role of Epstein-Barr Virus in development of breast cancer is frequently studied. In this regard, miRNAs are among the contributing elements in the molecular pathophysiology of EBV-related diseases. In addition, a growing number of host miRNAs are believed to be implicated in pathogenesis of breast cancer. MiR-218 is a tumor suppressive miRNA that is subjected to dysregulation in various EBV-associated cancers. We aimed to investigate the frequency of EBV and its relationship with expression status of tumor suppressive miR-218 in breast cancer and adjacent normal tissue.Methods:A total number of 51 fresh malignant breast cancer tissues (cases) and their adjacent normal tissues (controls) were collected. Nested-PCR and RT-qPCR were set to identify EBV frequency and miR-218 expression in cases and controls, respectively.Results:Out of all samples, 6.8% (7/102) comprising 11.6% (6/51) in malignant tissues and 1.9% (1/51) in normal control tissues were positive for EBV (P<0.05). Quantitative data showed that miR-218 was significantly downregulated in malignant tissues compared to control tissues (P<0.0001). In addition, reduced expression of miR-218 was associated with adverse clinical outcomes, metastasis, and higher grades of malignancy. Given the presence of EBV, lower expression of miR-218 was observed in breast cancer group in comparison with normal group (P<0.05). Conclusion:Our results raise the possibility of the relation between EBV infection and miR-218 downregulation in breast cancer and propose further investigations in this regard.

Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Cancer: Epidemiology, Mechanisms and Perspectives.

High-risk human papillomavirus (HR-HPV) is etiologically associated with the development and progression of cervical cancer, although other factors are involved. Epstein-Barr virus (EBV) detection in premalignant and malignant tissues from uterine cervix has been widely reported; however, its contribution to cervical cancer development is still unclear. Here, a comprehensive analysis regarding EBV presence and its potential role in cervical cancer, the frequency of EBV/HR-HPV coinfection in uterine cervix and EBV infection in tissue-infiltrating lymphocytes were revised. Overall, reports suggest a potential link of EBV to the development of cervical carcinomas in two possible pathways: (1) Infecting epithelial cells, thus synergizing with HR-HPV (direct pathway), and/or (2) infecting tissue-infiltrating lymphocytes that could generate local immunosuppression (indirect pathway). In situ hybridization (ISH) and/or immunohistochemical methods are mandatory for discriminating the cell type infected by EBV. However, further studies are needed for a better understanding of the EBV/HR-HPV coinfection role in cervical carcinogenesis.

The Role of Epstein-Barr Virus in Adults With Bronchiectasis: A Prospective Cohort Study.

BackgroundEpstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression.MethodsWe collected induced sputum in healthy controls and spontaneous sputum at 3–6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction.ResultsWe collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P = .001), but not viral loads (mean log10 load, 4.45 vs 4.76; P = .266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P = .393) nor load (mean log10 load, 4.34 vs 4.45; P = .580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1β (P = .002), CXC motif chemokine-8 (P = .008), and tumor necrosis factor–α levels (P = .005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P < .05) than those without. Detection of EBV DNA was unrelated to influenza virus and opportunistic bacteria (all P > .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous.ConclusionsPatients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression.

Sinonasal or nasopharyngeal undifferentiated Carcinoma?: diagnostic pitfall and the role of Epstein-Barrvirus (EBV) and human papillomavirus(HPV) examination

Undifferentiated carcinoma of the head and neck is frequently observed in nasopharynx, however it may also occur in oropharynx, salivary gland and sinonasal. Overlapping lesions in those regionscreate difficulty in determining the origin of the tumor. Thus, it causes diagnostic pitfall not only for pathologists, but also for clinicians. A 40 yearold man, presented with nasal obstruction, epistaxis, diplopia, and headache for a yearand showed nasal cavitysinistra and nasopharynx masses on CT-scan. Lymph node enlargement was not detected. First biopsywas performed and histopathologically diagnosed as nasopharyngeal undifferentiated carcinoma(NPC), extended into nasal cavity. Chemo-radiation protocol for NPC was conducted, and showing uncomplete response. Second biopsy was done, and reviewed with the first biopsy result. Thetumourwas arranged insolid, syncytial and trabecular pattern, with vesicular nuclei, prominent nucleoli, and lack of lymphoplasmacytic infiltrat. Immunohistochemistry (IHC) analysis of p16, EBNA1 and LMP1 were negative. PCR analysis of HPV-18 was positive, while EBV detection showed negative result. General association of EBV with NPC suggests that the presence of latent EBV infection can serve as a positive marker for NPC. Therefore, in this case, the EBV negativity and strong HPV association led to diagnosis of SNUC. The distinction of sinonasal undifferentiated carcinoma (SNUC) or from NPC was important for appropriate management and therapy.

Role of Epstein-Barr Virus in Pathogenesis and Racial Distribution of IgA Nephropathy.

IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circulating immune complexes with nephritogenic consequences. Because human B cells infected in vitro with Epstein-Barr virus (EBV) secrete galactose-deficient IgA1, we examined peripheral blood B cells from adult IgAN patients, and relevant controls, for the presence of EBV and their phenotypic markers. We found that IgAN patients had more lymphoblasts/plasmablasts that were surface-positive for IgA, infected with EBV, and displayed increased expression of homing receptors for targeting the upper respiratory tract. Upon polyclonal stimulation, these cells produced more galactose-deficient IgA1 than did cells from healthy controls. Unexpectedly, in healthy African Americans, EBV was detected preferentially in surface IgM- and IgD-positive cells. Importantly, most African Blacks and African Americans acquire EBV within 2 years of birth. At that time, the IgA system is naturally deficient, manifested as low serum IgA levels and few IgA-producing cells. Consequently, EBV infects cells secreting immunoglobulins other than IgA. Our novel data implicate Epstein-Barr virus infected IgA+ cells as the source of galactose-deficient IgA1 and basis for expression of relevant homing receptors. Moreover, the temporal sequence of racial-specific differences in Epstein-Barr virus infection as related to the naturally delayed maturation of the IgA system explains the racial disparity in the prevalence of IgAN.

Viral hepatitis B, C and infectious mononucleosis: epidemiological similarities and differences.

The presence of etiologically unencrypted diagnoses in the structure of viral hepatitis determines the relevance of searching for other pathogens involved in liver pathology formation. The role of Epstein-Barr virus in the development of hepatitis was described in the scientific literature, but official statistics do not allow to assess its contribution to liver damage along with hepatitis B and C viruses. The purpose - to identify common and distinctive epidemiological features of viral hepatitis B (HB), C (HC) and infectious mononucleosis (IM). A retrospective epidemiological analysis of these nosologies incidence was carried out according to official statistics in 2009-2018 in the Russian Federation. The multidirectional trends in the long-term dynamics of the incidence of IM, acute and chronic HB and HC and the presence of strong direct correlation between the acute and chronic HB and HC incidence were established. Distinctive features include disparity in epidemic process intensity in different age groups (prevalence of morbidity in children aged 1-2 and 3-6 years with IM and persons older than 18 years - with viral hepatitis). It is common for IM and HB and HC to involve the majority of urban population in the epidemic process, as well as children under the age of 1 year. The described differences are due to the action of transmission mechanisms specific to each infection. The results obtained in this study may serve as a basis for further study of the interaction of EpsteinBarr virus with hepatitis B and C viruses.

Clinical features of Epstein-Barr virus in the intestinal mucosa and blood of patients with inflammatory bowel disease.

Background:The role of Epstein–Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD.Methods:Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled. The EBV-DNA load in blood samples from each subject was analyzed by quantitative real-time polymerase chain reaction. EBV-encoded small-RNA 1 (EBER-1) was detected by in-situ hybridization in intestinal mucosa tissue sections of patients with IBD.Result:EBV-DNA was detected in 48 out of 568 patients with IBD (8.4%), and EBER-1 positivity was detected in 27 of these patients (56.3%). Refractory IBD and severe mucosal inflammation were more common in patients with detectable levels of EBER-1 than in those without; the number of EBER-1-positive cells positively correlated with mucosal inflammation (P value < 0.05). Age (≥60 years old) and use of azathioprine were risk factors for EBV infection. There was no significant difference in clinical remission rate and surgical rate between the EBER-1 positive group and EBER-1 negative group, antiviral group and the non-antiviral group, among IBD patients who tested positive for EBV-DNA.Conclusion:Elderly patients with IBD, treated with azathioprine, are more susceptible to EBV positivity. Further, EBV mucosal detection correlated with the severity of mucosal damage and refractoriness, but not prognosis.

The role of Epstein-Barr viral infection and hepatitis B and C in liver pathology.

A review of scientific literature data on clinical and epidemiological characterization of viral hepatitis B, C and Epstein-Barr viral infection is presented. Scopus, Web of Science, MedLine, The Cochrane Library, PubMed, CyberLeninka, RSCI databases were used to find the necessary literature. It was shown that Epstein-Barr virus along with hepatitis B and C viruses plays a significant role in the development of virus-mediated autoimmune liver diseases, as well as other organs (intestine, heart, kidneys, thyroid gland, etc.). The similarity of these nosologies is also evident in the nature of the course of the disease: the presence of a primary infection in a manifest or latent form, with possible subsequent chronization of the process and its periodic reactivation. Wide distribution of pathogens in the human population determines the possibility of mixed infections with Epstein-Barr virus and hepatitis B and C viruses, however, this problem has not been adequately described in the scientific literature. The review suggests that the role of Epstein-Barr virus in the development of liver diseases and extrahepatic pathology should not be ignored, and the combination of this pathogen with hepatitis B and C viruses required further in-depth studies.

The Global Landscape of EBV-Associated Tumors.

Epstein-Barr virus (EBV), a gamma-1 herpesvirus, is carried as a life-long asymptomatic infection by the great majority of individuals in all human populations. Yet this seemingly innocent virus is aetiologically linked to two pre-malignant lymphoproliferative diseases (LPDs) and up to nine distinct human tumors; collectively these have a huge global impact, being responsible for some 200,000 new cases of cancer arising worldwide each year. EBV replicates in oral epithelium but persists as a latent infection within the B cell system and several of its diseases are indeed of B cell origin; these include B-LPD of the immunocompromised, Hodgkin Lymphoma (HL), Burkitt Lymphoma (BL), Diffuse Large B cell Lymphoma (DLBCL) and two rarer tumors associated with profound immune impairment, plasmablastic lymphoma (PBL) and primary effusion lymphoma (PEL). Surprisingly, the virus is also linked to tumors arising in other cellular niches which, rather than being essential reservoirs of virus persistence in vivo, appear to represent rare cul-de-sacs of latent infection. These non-B cell tumors include LPDs and malignant lymphomas of T or NK cells, nasopharyngeal carcinoma (NPC) and gastric carcinoma of epithelial origin, and leiomyosarcoma, a rare smooth muscle cell tumor of the immunocompromised. Here we describe the main characteristics of these tumors, their distinct epidemiologies, histological features and degrees of EBV association, then consider how their different patterns of EBV latency may reflect the alternative latency programmes through which the virus first colonizes and then persists in immunocompetent host. For each tumor, we discuss current understanding of EBV's role in the oncogenic process, the identity (where known) of host genetic and environmental factors predisposing tumor development, and the recent evidence from cancer genomics identifying somatic changes that either complement or in some cases replace the contribution of the virus. Thereafter we look for possible connections between the pathogenesis of these apparently different malignancies and point to new research areas where insights may be gained.

DETECTION OF EPSTEIN-BARR VIRUS GENOME IN ORAL CAVITY SQUAMOUS CELL CARCINOMA SAMPLES OF RUSSIAN PATIENTS

Oral cavity squamous cell carcinoma (OC-SCC) is the most common and aggressive malignancy of the oral cavity. Recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for oral squamous cell carcinoma development, while distinguished role of Epstein-Barr virus (EBV) remains still uncertain. However, the evidence for association between virus infection and risk of oral squamous cell carcinoma is controversially and varies significantly by geographic regions and race. The aim of the present study was to elucidate the prevalence of HPV and EBV in OC-SCC samples of Russian patients from Moscow region. We investigated fresh-frozen tumor tissue fragments obtained from 11 patients with OC-SCC. DNA was extracted and the viral genome was examined by quantitative PCR assays with highrisk type-specific HPV and EBV specific markers followed by sequencing-based analysis. No HPV infection in analyzed OC-SCC samples was observed, while EBV was identified in 70.0% (7/10) of patients. Further based on Q-PCR amplification of the EBV targets including BamHI-W, EBNA1 and C-terminal fragment of LMP1 gene, EBV infection and measurement of virus load in the tumor samples was assessed. Sequencing LMP1-positive products revealed that the most samples (5/6) contained variants LMP1 with Cao deletion characterized by an increased transforming potential. These data suggest that prevalence of EBV infections is common and may influence cancer development, although detected LMP1 variants of EBV are not necessarily associated with the pathogenesis of OC-SCC. Further studies are necessary to determine the potential role of EBV and its possible importance as an infection factor in OC-SCC.

New role of Epstein-Barr virus in pathogenesis of acute and chronic lymphocytic leukemia

Abstract Acute lymphoblastic leukemia (ALL) is the most common mortal cancer in children. Chronic lymphocytic leukemia (CLL) is the most prevalent form of adult leukemia in western countries. B lymphocytes dominate the origin of both diseases. We have found a possible role for Epstein-Barr virus (EBV) in the origins of both ALL and CLL. We applied our strategy (Nat Genet 50:699, 2018) to determine whether the binding of EBV transcription factors (TFs) was concentrate at the 84 known risk loci for CLL and 16 loci for ALL. We evaluated 52 virally encoded TF ChIP-seq (chromatin immunoprecipitation with DNA sequencing) datasets and complemented this analysis with the results from 1535 human TF ChIP-seq datasets. We found that Epstein-Barr nuclear antigen leader protein (EBNALP), EBNA3C and EBNA2 were concentrated in the CLL loci by 3.7, 3.7 and 3.5-fold with p=4.89*10−19, p=2.74*10−11 and p=1.07*10−8, respectively. The viral (n=3) and human TFs (n=40) cluster together in an optimal subset of ~15 of the 84 known loci in CLL at p&amp;lt;10−6. Eighty percent of the most highly associated viral and human TF ChIP-seq datasets were collected from EBV transformed B cell lines in the Latency III program of viral expression, for which EBNALP, EBNA3C and EBNA2 are viral gene products. In ALL 3 of 16 loci were occupied by EBNA3ABC by a 17.7-fold enrichment with p=2.0*10−10. Among human TFs only c-MYC reached statistical significance binding 2 non-overlapping risk loci with 28.4-fold enrichment with p=2.9*10−10. These results nominate EBV for a role in the pathogenesis of CLL and ALL by a mechanism operating in transformed B cells through the EBV Latency III program of viral expression.

LMP1 and 2A Induce the Expression of Nrf2 Through Akt Signaling Pathway in Epstein-Barr Virus–Transformed B Cells

The transcription factor Nrf2, which regulates the expression of antioxidant and cytoprotective enzymes, contributes to cell proliferation and resistance to chemotherapy. Nrf2 is also dysregulated in many cancers such as lung, head and neck, and breast cancers, but its role in Epstein-Barr virus (EBV)–transformed B cells is still not understood. Here, we investigated EBV infection-induced Nrf2 activation in B cells by analyzing translocation of Nrf2 from the cytosol to the nucleus. In addition, we confirmed expression of the target genes in response to increased Nrf2 activation in EBV-transformed B cells. We demonstrated that knockdown of LMP1 and 2A blocks the translocation of Nrf2 to the nucleus and reduces ROS production in EBV-transformed B cells. Further, we showed that inhibition of Akt prevents Nrf2 activation. Moreover, knockdown of Nrf2 induces apoptotic cell death in EBV-transformed B cells. In conclusion, our study demonstrates that Nrf2 promotes proliferation of EBV-transformed B cells through the EBV-related proteins LMP1 and 2A and Akt signaling, implicating Nrf2 as a potential molecular target for EBV-associated disease.

Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Oral and Anogenital Carcinogenesis: Potential Tumorigenic Pathways.

Epstein-Barr virus (EBV) and human papillomavirus (HPV) have been implicated in 38% of all virus-related cancers. Over the past three decades, both have been detected in anogenital and head-and-neck squamous cell carcinomas (HNSCC), with evidence of involvement in tumor genesis and progression. Very little has been published on HPV/EBV coinfection. In this chapter, we review the literature on the role of these viruses in oral carcinoma and draw parallels with other HNSCCs and anogenital carcinomas, with emphasis on their interplay and potential signaling pathways. EBV infection seems to create an environment that favors HPV latency, supporting the claim that EBV is a cofactor in HPV-related carcinomas. In turn, under certain circumstances, HPV appears to be able to induce EBV to switch to the latent or replicative state. The main viral oncogenes expressed in these malignancies are EBNA1, EBNA2, LMP1, EBERs, and the high-risk HPV oncogenes E6 and E7. The most well-documented human proteins involved are p53, pRb, p16INK4a, p19ARF, Myc, E-cadherin, β-catenin, EGFR, MLH1, and COX-2. These proteins are directly associated not only with viral products but also with one another in the development of malignancy. Knowledge of the molecular machinery behind carcinomas coinfected with HPV and EBV may help understand how these viruses trigger carcinogenesis and subsidize the development of new biomarkers of tumor aggressiveness and prognosis, alternative surrogate virus markers, and possible therapeutic targets.

The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging.

Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus (EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.

Refractory inflammatory bowel disease: is there a role for Epstein-Barr virus? A case-controlled study using highly sensitive Epstein-Barr virus–encoded small RNA1 in situ hybridization

A potential role for viral infections has been implicated in inflammatory bowel disease (IBD) unresponsive to medical treatment. It is well known that Epstein-Barr virus (EBV) infection can elicit a brisk mononuclear response in the gastrointestinal tract. The aim of this study was to further evaluate the role of EBV in patients with refractory IBD and compare them with nonrefractory IBD cases. Surgically resected colonic specimens from 67 patients with refractory IBD (62 with ulcerative colitis, 3 patients with Crohn disease, and 2 patients with indeterminate colitis) were retrieved. Twelve colectomy specimens from patients with ulcerative colitis who had undergone resections for dysplasia or endometriosis were included as controls. Highly sensitive EBV-encoded small RNA1 (EBER-1) in situ hybridization was performed on a representative block from each specimen. EBER-1 reactivity was graded as absent, focal, or diffuse. EBV was detected in 60% (40/67) of patients with refractory IBD compared with 25% (3/12) of the control group (P < .05). Focal EBER-1 positivity was present in 45% of cases of refractory IBD compared with 25% of controls. Diffuse EBER-1 reactivity was seen in 15% of cases of refractory IBD (10/67); none of the samples from the control group contained diffuse EBER-1 positivity. There was a positive correlation between EBER positivity and depth of inflammation and mucosal ulceration in patients with refractory IBD. Our findings suggest a potential role for EBV infection in patients with refractory IBD.

Role of Epstein-Barr Virus in the Pathogenesis of Head and Neck Cancers and Its Potential as an Immunotherapeutic Target.

The role of Epstein–Barr virus (EBV) infection in the development and progression of tumor cells has been described in various cancers. Etiologically, EBV is a causative agent in certain variants of head and neck cancers such as nasopharyngeal cancer. Proteins expressed by the EVB genome are involved in invoking and perpetuating the oncogenic properties of the virus. However, these protein products were also identified as important targets for therapeutic research in the past decades, particularly within the context of immunotherapy. The adoptive transfer of EBV-targeted T-cells as well as the development of EBV vaccines has opened newer lines of research to conceptualize novel therapeutic approaches toward the disease. This review addresses the most important aspects of the association of EBV with head and neck cancers from an immunological perspective. It also aims to highlight the current and future prospects of enhanced EBV-targeted immunotherapies.

The Relationship Between EBV Virus and Breast Cancer in Khuzestan Province of Iran

Introduction: Many study results have suggested that infection by the Epstein-Barr virus is a possible agent of human breast cancer. But the role of Epstein-Barr virus in breast cancer is still controversial. Materials and Methods: Paraffin embedded formalin fixed specimens were prepared from 40 breast and 40 healthy tissues in Khuzestan province of Iran. After DNA extraction, the purity of all DNA samples was evaluated by amplification of constitutive beta-actin gene. Then the presence of EBV gene in DNA extraction with appropriate purity was assessed by polymerase chain reaction (PCR) using virus specific primers. Results: only 2 out 39 cases of tumor (5.12%) and none of the 37 healthy samples were positive for the presence of Epstein-Barr virus. Statistically, Cramer’s index for EBV infection was 0.160 in cancer samples. Conclusions: Our results indicated that there is no significant relationship between breast cancer and Epstein-Barr virus. Further investigation on more patients needed to determine the exact relationship between EBV and breast cancer in this province.