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EBV reactivation

Octavia Ramayanti, Mitch Brinkkemper, Sandra A W M Verkuijlen, Leni Ritmaleni, Mei Lin Go, Jaap M Middeldorp
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA...
March 22, 2018: Cancers
Eveline Hoebe, Coral Wille, Stacy Hagemeier, Shannon Kenney, Astrid Greijer, Jaap Middeldorp
Epstein-Barr Virus (EBV) BamHI-A rightward frame 1 (BARF1) protein is considered a viral oncogene in epithelial cells and has immune-modulating properties. During viral lytic replication BARF1 is expressed as an early gene, regulated by the immediate early EBV protein R. However, in viral latency BARF1 is exclusively expressed in epithelial tumors such as nasopharyngeal (NPC) and gastric carcinoma (GC) but not in lymphomas, indicating that activation of the BARF1 promoter is cell type specific. Undifferentiated NPC is characterized by high expression of ΔNp63 isoforms of the epithelial differentiation marker p63, a member of the p53 family of transcription factors...
March 17, 2018: Cancers
Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
Eman Farid, Mohammed Al-Biltagi
In Bahrain, adequate epidemiological information is lacking concerning the rate of EBV infection, which could be helpful in order to develop measures to protect against EBV infections. The aim of this study, was to investigate the trend of EBV infection in Bahrain over a 15-year period, 2001-2015. The EBV serological results of 10 560 patients with possible EBV infection were evaluated. Samples taken at the Salmaniya Medical Complex during 2001-2015 were included. The presence or absence of EBV viral capsid antigen (VCA) IgG, VCA IgM and EBV nuclear antigen (EBNA) IgG antibodies was recorded...
March 5, 2018: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
Kimberly Boyd, Joshua M Harrison, Michael J Kavanaugh
The heterophile antibody (Monospot), initial test of choice for Epstein-Barr virus (EBV)-associated infectious mononucleosis, is both sensitive (70-92%) and specific (96-100%). False positives have been demonstrated in cases of viral hepatitis, human immunodeficiency virus, leukemia, lymphoma, pancreatic cancer, systemic lupus erythematosus, and rubella. We present a case of a 46-yr-old male who developed fever, chills, headaches, myalgia, fatigue, and photophobia 1 d after returning from the Philippines. He demonstrated a mild transaminitis and significant thrombocytopenia (12,000 cells/μL)...
March 1, 2018: Military Medicine
Zhiwei Liu, Anna E Coghill, Ruth M Pfeiffer, Carla Proietti, Wan-Lun Hsu, Yin-Chu Chien, Lea Lekieffre, Lutz Krause, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Jason Mulvenna, Jaap M Middeldorp, Jeff Bethony, Chien-Jen Chen, Denise L Doolan, Allan Hildesheim
Background: Little is known about variation in antibody response targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk. Methods: We utilized a microarray to measure IgG and IgA antibody responses against 199 EBV protein sequences from five EBV strains in 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the association between environmental and genetic risk factors and variation in antibody responses...
March 2, 2018: Journal of Infectious Diseases
Nicole Hartwig Trier, Bettina Eide Holm, Julie Heiden, Ole Slot, Henning Locht, Hanne Lindegaard, Anders Svendsen, Christoffer Tandrup Nielsen, Søren Jacobsen, Elke Theander, Gunnar Houen
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay. One peptide, only found in a single strain (AG876), obtained a sensitivity and specificity of 77% and 95%, respectively and showed high sequence similarity to the filaggrin peptide originally used for ACPA detection...
February 27, 2018: Scientific Reports
Mahiuddin Ahmed, Andres Lopez-Albaitero, Dmitry Pankov, Brian H Santich, Hong Liu, Su Yan, Jingyi Xiang, Pei Wang, Aisha N Hasan, Annamalai Selvakumar, Richard J O'Reilly, Cheng Liu, Nai-Kong V Cheung
EBV infection is associated with a number of malignancies of clinical unmet need, including Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, and posttransplant lymphoproliferative disease (PTLD), all of which express the EBV protein latent membrane protein 2A (LMP2A), an antigen that is difficult to target by conventional antibody approaches. To overcome this, we utilized phage display technology and a structure-guided selection strategy to generate human T cell receptor-like (TCR-like) monoclonal antibodies with exquisite specificity for the LMP2A-derived nonamer peptide, C426LGGLLTMV434 (CLG), as presented on HLA-A*02:01...
February 22, 2018: JCI Insight
Maria J García-Barchino, Maria E Sarasquete, Carlos Panizo, Julie Morscio, Antonio Martinez, Miguel Alcoceba, Vicente Fresquet, Blanca Gonzalez-Farre, Bruno Paiva, Ken H Young, Eloy F Robles, Sergio Roa, Jon Celay, Marta Larrayoz, Davide Rossi, Gianluca Gaidano, Santiago Montes-Moreno, Miguel A Piris, Ana Balanzategui, Cristina Jimenez, Idoia Rodriguez, Maria J Calasanz, Maria J Larrayoz, Victor Segura, Ricardo Garcia-Muñoz, Maria P Rabasa, Shuhua Yi, Jianyong Li, Mingzhi Zhang, Zijun Y Xu-Monette, Noemi Puig-Moron, Alberto Orfao, Sebastian Böttcher, Jesus M Hernandez-Rivas, Jesus San Miguel, Felipe Prosper, Thomas Tousseyn, Xavier Sagaert, Marcos Gonzalez, Jose A Martinez-Climent
The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine or other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In comparison to EBV-negative tumors, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL and exhibited CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal center DLBCL phenotype, EBV latency programs type II/III, and a very short survival...
February 21, 2018: Journal of Pathology
Yufeng Chen, Yifei Xu, Weilin Zhao, Xue Xiao, Xiaoying Zhou, Longde Lin, Tingting Huang, Jian Liao, Yancheng Li, Xiaoyun Zeng, Guangwu Huang, Weimin Ye, Zhe Zhang
BACKGROUND: Subjects with elevated Epstein-Barr virus (EBV) immunoglobulin A (IgA) titers have a higher risk of developing nasopharyngeal carcinoma (NPC), indicating that reactivation of EBV in the local mucosa might be important for NPC carcinogenesis. Cigarette smoking appears to be one of the environmental risk factors for NPC. However, it remains unclear whether smoking-induced nasopharyngeal carcinogenesis acts through reactivating EBV in the nasopharyngeal mucosa. Therefore, this study aims to investigate the association between cigarette smoking and nasopharyngeal EBV reactivation in a NPC high-risk population...
February 14, 2018: BMC Cancer
Maren Bieling, Sabine Tischer, Ulrich Kalinke, Rainer Blasczyk, Søren Buus, Britta Maecker-Kolhoff, Britta Eiz-Vesper
Morbidity and mortality of immunocompromised patients are increased by primary infection with or reactivation of Epstein-Barr virus (EBV), possibly triggering EBV+ post-transplant lymphoproliferative disease (PTLD). Adoptive transfer of EBV-specific cytotoxic T cells (EBV-CTLs) promises a non-toxic immunotherapy to effectively prevent or treat these complications. To improve immunotherapy and immunomonitoring this study aimed at identifying and evaluating naturally processed and presented HLA-A*03:01-restricted EBV-CTL epitopes as immunodominant targets...
January 12, 2018: Oncotarget
Juan C Ramos, Joseph A Sparano, Michelle A Rudek, Page C Moore, Ethel Cesarman, Erin G Reid, David Henry, Lee Ratner, David Aboulafia, Jeanette Y Lee, Richard F Ambinder, Ronald Mitsuyasu, Ariela Noy
INTRODUCTION: Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV+) or human herpesvirus-8-positive (HHV-8+) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). PATIENTS AND METHODS: We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule...
February 2, 2018: Clinical Lymphoma, Myeloma & Leukemia
Volker Strenger, Gerald Merth, Herwig Lackner, Stephan W Aberle, Harald H Kessler, Markus G Seidel, Wolfgang Schwinger, Daniela Sperl, Petra Sovinz, Anna Karastaneva, Martin Benesch, Christian Urban
Haemophagocytic lymphohistiocytosis (HLH) is a possibly life-threatening syndrome of immune dysregulation and can be divided into primary (hereditary) and secondary forms (including malignancy-associated HLH (M-HLH)). We retrospectively analysed epidemiological, clinical, virological and laboratory data from patients with M-HLH treated at our department between 1995 and 2014. Out of 1.706 haemato-/oncologic patients treated at our department between 1995 and 2014, we identified 22 (1.29%) patients with secondary HLH (1...
February 6, 2018: Annals of Hematology
Marco Bo, Magdalena Niegowska, Gian Luca Erre, Marco Piras, Maria Giovanna Longu, Pierangela Manchia, Mario Manca, Giuseppe Passiu, Leonardo A Sechi
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive joint damage due to largely unknown environmental factors acting in concert with risk alleles conferring genetic susceptibility. A major role has been attributed to viral infections that include past contacts with Epstein-Barr virus (EBV) and, more recently, to non-protein coding sequences of human endogenous retrovirus K (HERV-K) integrated in the human genome. Molecular mimicry between viral and self proteins is supposed to cause the loss of immune tolerance in predisposed hosts...
January 29, 2018: Scientific Reports
Paola Cavalcante, Claudia Barzago, Fulvio Baggi, Carlo Antozzi, Lorenzo Maggi, Renato Mantegazza, Pia Bernasconi
Pathogen infections and dysregulated Toll-like receptor (TLR)-mediated innate immune responses are suspected to play key roles in autoimmunity. Among TLRs, TLR7 and TLR9 have been implicated in several autoimmune conditions, mainly because of their ability to promote abnormal B cell activation and survival. Recently, we provided evidence of Epstein-Barr virus (EBV) persistence and reactivation in the thymus of myasthenia gravis (MG) patients, suggesting an involvement of EBV in the intrathymic pathogenesis of the disease...
January 24, 2018: Annals of the New York Academy of Sciences
Dong-Wen Lv, Kun Zhang, Renfeng Li
Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein (ICSBP), is a transcription factor of the IRF family. IRF8 plays a key role in normal B cell differentiation, a cellular process that is intrinsically associated with Epstein-Barr virus (EBV) reactivation. However, whether IRF8 regulates EBV lytic replication remains unknown. In this study, we utilized a CRISPR/Cas9 genomic editing approach to deplete IRF8 and found that IRF8 depletion dramatically inhibits the reactivation of EBV upon lytic induction...
January 22, 2018: PLoS Pathogens
Marco Bo, Gian Luca Erre, Magdalena Niegowska, Marco Piras, Loredana Taras, Maria Giovanna Longu, Giuseppe Passiu, Leonardo A Sechi
OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease characterised by a pro-inflammatory cytokines linked erosive joint damage and by humoral and cellular response against a broad range of self-peptides. Molecular mimicry between Epstein-Barr virus (EBV), Mycobacterium avium subsp. paratuberculosis (MAP) and host peptides has long been regarded as an RA pathogenetic mechanism. Using bioinformatic analysis we identified high sequence homology among interferon regulatory factor 5 (IRF5), EBV antigen BOLF1 and MAP antigen MAP_4027...
January 15, 2018: Clinical and Experimental Rheumatology
Michael D Abendroth, Michael G Bayerl, Michael J Wilkinson, David F Claxton, Charles S Specht
We report a rare case of Epstein-Barr virus (EBV)-positive polymorphic B-cell lymphoproliferative disorder (LPD) involving the lacrimal gland of a 28-year-old, apparently immunocompetent woman. She presented with a chief complaint of orbital swelling and tenderness and was found to have a lesion involving the right lacrimal gland and distal superior and lateral rectus muscles. Histology of the lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and scattered cells that resembled the Reed-Sternberg (R-S) cells of classical Hodgkin lymphoma...
December 2017: Ocular Oncology and Pathology
L-L Zuo, J Zhang, L-Z Liu, Q Zhou, S-J Du, S-Y Xin, Z-P Ning, J Yang, H-B Yu, W-X Yue, J Wang, F-X Zhu, G-Y Li, J-H Lu
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203...
December 22, 2017: Oncogenesis
Akane Kunitomi, Yuta Hasegawa, Naoko Asano, Seiichi Kato, Takashi Tokunaga, Yasuhiko Miyata, Hiroatsu Iida, Hirokazu Nagai
A 70-year-old woman with lymphadenopathy was admitted to hospital in 2008. Lymph node biopsy showed reactive lymphoid hyperplasia (RH) with monoclonal proliferation of EBV. Her lymphadenopathy regressed without treatment. In 2014, the patient presented with nasal obstruction because of a left nasal mass. She was diagnosed with EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly based on the examination of a biopsy specimen of the mass. The IgH rearrangement in the specimens from the 2008 and the 2014 revealed that they were genetically identical...
December 27, 2017: Internal Medicine
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