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      Epstein–Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update

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          Abstract

          The Epstein–Barr virus (EBV) is a DNA lymphotropic herpesvirus and the causative agent of infectious mononucleosis. EBV is highly prevalent since it affects more than 90% of individuals worldwide and has been linked to several malignancies including PTLDs, which are one of the most common malignancies following transplantation. Among all the EBV genes, most of the recent investigations focused on studying the LMP-1 oncogene because of its high degree of polymorphism and association with tumorigenic activity. There are two main EBV genotypes, Type 1 and 2, distinguished by the differences in the EBNA-2 gene. Further sub genotyping can be characterized by analyzing the LMP-1 gene variation. The virus primarily transmits through oral secretions and persists as a latent infection in human B-cells. However, it can be transmitted through organ transplantations and blood transfusions. In addition, symptoms of EBV infection are not distinguishable from other viral infections, and therefore, it remains questionable whether there is a need to screen for EBV prior to blood transfusion. Although the process of leukoreduction decreases the viral copies present in the leukocytes, it does not eliminate the risk of EBV transmission through blood products. Here, we provide a review of the EBV epidemiology and the genetic variability of the oncogene LMP-1. Then, we underscore the findings of recent EBV seroprevalence and viremia studies among blood donors as a highly prevalent transfusion transmissible oncovirus.

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          Epstein-Barr virus: more than 50 years old and still providing surprises.

          It is more than 50 years since the Epstein-Barr virus (EBV), the first human tumour virus, was discovered. EBV has subsequently been found to be associated with a diverse range of tumours of both lymphoid and epithelial origin. Progress in the molecular analysis of EBV has revealed fundamental mechanisms of more general relevance to the oncogenic process. This Timeline article highlights key milestones in the 50-year history of EBV and discusses how this virus provides a paradigm for exploiting insights at the molecular level in the diagnosis, treatment and prevention of cancer.
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            Persistence of the Epstein-Barr virus and the origins of associated lymphomas.

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              Lymphomas after solid organ transplantation: a collaborative transplant study report.

              We used the Collaborative Transplant Study database to analyze the incidence, risk, and impact of malignant lymphomas in approximately 200,000 organ transplant recipients. Over a 10-year period, the risk in renal transplant recipients was 11.8-fold higher than that in a matched nontransplanted population (p<0.0001). The majority of lymphomas were diagnosed after the first post-transplant year. Heart-lung transplants showed the highest relative risk (RR 239.5) among different types of organ transplants. In kidney recipients, immunosuppression with cyclosporine did not confer added risk compared with azathioprine/steroid treatment, whereas treatment with FK506 increased the risk approximately twofold. Induction therapy with OKT3 or ATG, but not with anti-IL2 receptor antibodies, increased the risk of lymphoma during the first year. Antirejection therapy with OKT3 or ATG also increased the risk. First-year mortality in renal and heart transplant patients with lymphoma was approximately 40% and 50%, respectively, and showed no improvement in recent years. A pattern of preferential localization to the vicinity of the transplant was noted, and the prognosis of the patient was related to localization. This study highlights the continuing risk for lymphoma with time post-transplantation, the contribution of immunosuppression to increased risk, and continuing poor outcomes in patients with post-transplant lymphoma.
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                Author and article information

                Contributors
                URI : https://frontiersin.org/people/u/528937
                URI : https://frontiersin.org/people/u/528944
                URI : https://frontiersin.org/people/u/102093
                URI : https://frontiersin.org/people/u/433584
                URI : https://frontiersin.org/people/u/27475
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                13 June 2018
                2018
                : 8
                : 211
                Affiliations
                [1] 1Biomedical Research Center, Qatar University , Doha, Qatar
                [2] 2Department of Biomedical Science, College of Health Sciences, Qatar University , Doha, Qatar
                [3] 3Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University , Doha, Qatar
                Author notes

                Edited by: Gerburg Wulf, Harvard Medical School, United States

                Reviewed by: Mohammad Imran Khan, King Abdulaziz University, Saudi Arabia; Jiping Yue, University of Chicago, United States

                *Correspondence: Gheyath K. Nasrallah, gheyath.nasrallah@ 123456qu.edu.qa

                These authors have contributed equally to this work.

                Specialty section: This article was submitted to Cancer Epidemiology and Prevention, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2018.00211
                6008310
                29951372
                ea647a47-f98f-4747-9e76-4ff872e3998e
                Copyright © 2018 Smatti, Al-Sadeq, Ali, Pintus, Abou-Saleh and Nasrallah.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 February 2018
                : 24 May 2018
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 163, Pages: 16, Words: 13500
                Funding
                Funded by: Qatar National Research Fund 10.13039/100008982
                Award ID: UREP18-001-3-001
                Funded by: Qatar University 10.13039/501100004252
                Award ID: QUCG-CHS-2018\2019-1
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                blood donors,epstein–barr virus,lmp-1 oncogene,seroprevalence,transfusion,viremia

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