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https://www.readbyqxmd.com/read/28333576/epstein-barr-virus-lytic-reactivation-activates-b-cells-polyclonally-and-induces-activation-induced-cytidine-deaminase-expression-a-mechanism-underlying-autoimmunity-and-its-contribution-to-graves-disease
#1
Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Hirotsugu Sugihara, Sayuri Hara, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Kazuhiko Hayashi
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity...
March 23, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28328987/a-novel-recombinant-variant-of-latent-membrane-protein-1-from-epstein-barr-virus-in-argentina-denotes-phylogeographical-association
#2
Magdalena Gantuz, Mario Alejandro Lorenzetti, Paola Andrea Chabay, María Victoria Preciado
AIM: To study LMP1 variants distribution among children with EBV+ malignant and benign conditions as well as in healthy carriers. METHODS: Oral secretions and blood cells from 31 children with IM, and biopsies from 14 EBV+ reactive lymphoid hyperplasia and 33 EBV+ lymphomas were included. LMP1 was amplified by nested PCR and sequenced. Phylogenetic reconstructions were made under Maximun Likelihood, Bayesian and coalescent algorithms. RESULTS: Six clades were defined (China1, China2, Med-, Alaskan, B95...
2017: PloS One
https://www.readbyqxmd.com/read/28280640/hhv8-ebv-coinfection-lymphoproliferative-disorder-rare-entity-with-a-favorable-outcome
#3
Dhouha Bacha, Beya Chelly, Houda Kilani, Lamia Charfi, Amel Douggaz, Samia Chatti, Emna Chelbi
HHV8/EBV-associated germinotropic lymphoproliferative disorder (GLD) is a challenging diagnosis given its rarity, the particular clinical presentation, and the lack of expression of markers usually used in establishing hematopoietic lineage. We report a new case of HHV8/EBV GLD in an immunocompetent 78-year-old woman. The diagnosis was made in an incidentally discovered lymphadenopathy. Histological examination showed a nodular lymphoid proliferation centered by aggregates of atypical plasmablastic cells admixed with small lymphoid cells...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28248818/kshv-associated-and-ebv-associated-germinotropic-lymphoproliferative-disorder-new-findings-and-review-of-the-literature
#4
Tapan Bhavsar, John C Lee, Yvonne Perner, Mark Raffeld, Liqiang Xi, Stefania Pittaluga, Elaine S Jaffe
We report 2 cases of Kaposi sarcoma-associated herpesvirus (KSHV)-and Epstein-Barr Virus (EBV) associated germinotropic lymphoproliferative disorder. Both cases arose in patients from regions endemic for KSHV, Cape Verde, and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of human herpesvirus 8 (HHV-8) positive multicentric Castleman disease...
February 28, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28240350/oncogenic-s1p-signalling-in-ebv-associated-nasopharyngeal-carcinoma-activates-akt-and-promotes-cell-migration-through-s1p-receptor-3
#5
Hui Min Lee, Kwok-Wai Lo, Wenbin Wei, Sai Wah Tsao, Grace Tin Yun Chung, Maha Hafez Ibrahim, Christopher W Dawson, Paul G Murray, Ian C Paterson, Lee Fah Yap
Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1 and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration...
February 27, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28222771/wogonin-as-a-targeted-therapeutic-agent-for-ebv-lymphoma-cells-involved-in-lmp1-nf-%C3%AE%C2%BAb-mir-155-pu-1-pathway
#6
Xue Wu, Ping Liu, Haijun Zhang, Yuan Li, Jumah Masoud Mohammad Salmani, Fei Wang, Ke Yang, Rong Fu, Zhewei Chen, Baoan Chen
BACKGROUND: Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future. METHODS: Cell proliferation was studied by CCK8...
February 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28179525/differentiation-dependent-lmp1-expression-is-required-for-efficient-lytic-ebv-reactivation-in-epithelial-cells
#7
Dhananjay M Nawandar, Makoto Ohashi, Reza Djavadian, Elizabeth Barlow, Kathleen Makielski, Ahmed Ali, Denis Lee, Paul F Lambert, Eric Johannsen, Shannon C Kenney
Epstein-Barr virus (EBV)-associated diseases of epithelial cells, including tumors such as nasopharyngeal carcinoma (NPC) that have latent infection, and oral hairy leukoplakia (OHL) lesions that have lytic infection, frequently express the viral latent membrane protein 1 (LMP1). In lytically-infected cells, LMP1 expression is activated by the BRLF1 (R) immediate-early (IE) protein. However, the mechanisms by which LMP1 expression is normally regulated in epithelial cells remain poorly understood, and its potential roles in regulating lytic reactivation in epithelial cells are as yet unexplored...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28118740/epstein-barr-virus-gene-expression-and-latency-pattern-in-gastric-carcinomas-a-systematic-review
#8
REVIEW
Joana Ribeiro, Cláudia Oliveira, Mariana Malta, Hugo Sousa
METHODS: A systematic review of literature was conducted to identify all published reports regarding the expression of Epstein-Barr Virus (EBV) proteins/transcripts and EBV latency patterns in EBV-associated gastric carcinomas (EBVaGC). RESULTS: The literature search retrieved 247 papers, of which 25 papers matched the inclusion criteria. The analysis reveals that the most frequently expressed EBV latent proteins are EBNA1 (98.1%) and LMP2A (53.8%), while LMP1 and LMP2B are present in only 10% of cases...
March 2017: Future Oncology
https://www.readbyqxmd.com/read/28110206/an-epstein-barr-virus-susceptible-immature-t-cell-line-will4-established-from-a-patient-with-t-lymphoblastic-lymphoma-bearing-cd21-and-a-clonal-ebv-genome
#9
Hiroki Hosoi, Ken-Ichi Imadome, Shinobu Tamura, Kodai Kuriyama, Shogo Murata, Yusuke Yamashita, Toshiki Mushino, Takehiro Oiwa, Hiroshi Kobata, Akinori Nishikawa, Hideki Nakakuma, Nobuyoshi Hanaoka, Yasushi Isobe, Kouichi Ohshima, Takashi Sonoki
We managed a patient with an Epstein-Barr virus-associated T-cell lymphoblastic lymphoma. Mediastinal tumor cells at initial admission were positive for CD4, CD8, and TdT. Interestingly, a lymph node at necropsy was compatible for a CD4-positive peripheral T-cell lymphoma without CD8 and TdT expression, suggesting a different phenotype from the mediastinal tumor. Tumor cells in pleural effusion continued to proliferate in in vitro and were designated as WILL4. WILL4 cells were positive for CD3, CD4, CD8, CD21, T-cell receptor (TcR) αβ, and TdT, indicating a similar phenotype to thymocytes...
January 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28098136/exome-and-genome-sequencing-of-nasopharynx-cancer-identifies-nf-%C3%AE%C2%BAb-pathway-activating-mutations
#10
Yvonne Y Li, Grace T Y Chung, Vivian W Y Lui, Ka-Fai To, Brigette B Y Ma, Chit Chow, John K S Woo, Kevin Y Yip, Jeongsun Seo, Edwin P Hui, Michael K F Mak, Maria Rusan, Nicole G Chau, Yvonne Y Y Or, Marcus H N Law, Peggy P Y Law, Zoey W Y Liu, Hoi-Lam Ngan, Pok-Man Hau, Krista R Verhoeft, Peony H Y Poon, Seong-Keun Yoo, Jong-Yeon Shin, Sau-Dan Lee, Samantha W M Lun, Lin Jia, Anthony W H Chan, Jason Y K Chan, Paul B S Lai, Choi-Yi Fung, Suet-Ting Hung, Lin Wang, Ann Margaret V Chang, Simion I Chiosea, Matthew L Hedberg, Sai-Wah Tsao, Andrew C van Hasselt, Anthony T C Chan, Jennifer R Grandis, Peter S Hammerman, Kwok-Wai Lo
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28077657/latent-membrane-protein-1-lmp1-and-lmp2a-collaborate-to-promote-epstein-barr-virus-induced-b-cell-lymphomas-in-a-cord-blood-humanized-mouse-model-but-are-not-essential
#11
Shi-Dong Ma, Ming-Han Tsai, James C Romero-Masters, Erik A Ranheim, Shane M Huebner, Jillian A Bristol, Henri-Jacques Delecluse, Shannon C Kenney
Epstein-Barr virus (EBV) infection is associated with B cell lymphomas in humans. The ability of EBV to convert human B cells into long-lived lymphoblastoid cell lines (LCLs) in vitro requires the collaborative effects of EBNA2 (which hijacks Notch signaling), latent membrane protein 1 (LMP1) (which mimics CD40 signaling), and EBV-encoded nuclear antigen 3A (EBNA3A) and EBNA3C (which inhibit oncogene-induced senescence and apoptosis). However, we recently showed that an LMP1-deleted EBV mutant induces B cell lymphomas in a newly developed cord blood-humanized mouse model that allows EBV-infected B cells to interact with CD4 T cells (the major source of CD40 ligand)...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28056887/therapeutic-vaccine-targeting-epstein-barr-virus-latent-protein-lmp1-suppresses-lmp1-expressing-tumor-growth-and-metastasis-in-vivo
#12
Mei-Chun Lin, Yong-Chong Lin, Syue-Ting Chen, Tai-Horng Young, Pei-Jen Lou
BACKGROUND: In endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine. METHODS: Animal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28053105/epstein-barr-virus-encoded-latent-membrane-protein-1-upregulates-glucose-transporter-1-transcription-via-the-mtorc1-nf-%C3%AE%C2%BAb-signaling-pathways
#13
Jun Zhang, Lin Jia, Weitao Lin, Yim Ling Yip, Kwok Wai Lo, Victoria Ming Yi Lau, Dandan Zhu, Chi Man Tsang, Yuan Zhou, Wen Deng, Hong Lok Lung, Maria Li Lung, Lai Man Cheung, Sai Wah Tsao
Accumulating evidence indicates that oncogenic viral protein plays a crucial role in activating aerobic glycolysis during tumorigenesis, but the underlying mechanisms are largely undefined. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a transmembrane protein with potent cell signaling properties and has tumorigenic transformation property. Activation of NF-κB is a major signaling pathway mediating many downstream transformation properties of LMP1. Here we report that activation of mTORC1 by LMP1 is a key modulator for activation of NF-κB signaling to mediate aerobic glycolysis...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28009988/a-neutralized-human-lmp1-igg-inhibits-enktl-growth-by-suppressing-the-jak3-stat3-signaling-pathway
#14
Yuan Mao, Jun Wang, Mingzhi Zhang, Weifei Fan, Qi Tang, Siping Xiong, Xiaojun Tang, Juqing Xu, Lin Wang, Shu Yang, Suyao Liu, Li Xu, Yan Chen, Lin Xu, Rong Yin, Jin Zhu
Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL)...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27993616/quantitative-multi-target-rna-profiling-in-epstein-barr-virus-infected-tumor-cells
#15
A E Greijer, O Ramayanti, S A W M Verkuijlen, Z Novalić, H Juwana, J M Middeldorp
Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts...
December 16, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27982024/epstein-barr-virus-positive-follicular-lymphoma
#16
Nicholas Mackrides, German Campuzano-Zuluaga, Yvan Maque-Acosta, Adrienne Moul, Nouf Hijazi, Francis Offiong Ikpatt, Ronald Levy, Ramiro E Verdun, Kranthi Kunkalla, Yasodha Natkunam, Izidore S Lossos, Francisco Vega, Jennifer Chapman
Epstein-Barr virus (EBV) -associated follicular lymphoma is only rarely reported. Herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of EBV-associated follicular lymphoma occurring in unselected cases. Out of 382 analyzed cases, 10 EBV-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3-4.0%). All EBV-positive follicular lymphomas showed EBV-encoded small RNA-positive lymphoma cells present in a follicular distribution. Of these, eight also had tissue available for testing of expression of latent membrane protein 1 (LMP1), out of which six (75%) were positive...
December 16, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27974566/cd63-regulates-epstein-barr-virus-lmp1-exosomal-packaging-enhancement-of-vesicle-production-and-noncanonical-nf-%C3%AE%C2%BAb-signaling
#17
Stephanie N Hurwitz, Dingani Nkosi, Meghan M Conlon, Sara B York, Xia Liu, Deanna C Tremblay, David G Meckes
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncoprotein that is packaged into small extracellular vesicles (EVs) called exosomes. Trafficking of LMP1 into multivesicular bodies (MVBs) alters the content and function of exosomes. LMP1-modified exosomes enhance the growth, migration, and invasion of malignant cells, demonstrating the capacity to manipulate the tumor microenvironment and enhance the progression of EBV-associated cancers. Despite the growing evidence surrounding the significance of LMP1-modified exosomes in cancer, very little is understood about the mechanisms that orchestrate LMP1 incorporation into these vesicles...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27926490/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#18
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903798/the-linear-ubiquitin-assembly-complex-modulates-latent-membrane-protein-1-activation-of-nf-%C3%AE%C2%BAb-and-interferon-regulatory-factor-7
#19
Ling Wang, Yujia Wang, Juan Zhao, Junping Ren, Kenton H Hall, Jonathan P Moorman, Zhi Q Yao, Shunbin Ning
Recently, linear ubiquitin assembly complex (LUBAC)-mediated linear ubiquitination has come into focus due to its emerging role in activation of NF-κB in different biological contexts. However, the role of LUBAC in LMP1 signaling leading to NF-κB and interferon regulatory factor 7 (IRF7) activation has not been investigated. We show here that RNF31, the key component of LUBAC, interacts with LMP1 and IRF7 in Epstein-Barr virus (EBV)-transformed cells and that LUBAC stimulates linear ubiquitination of NEMO and IRF7...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27900085/id1-upregulation-and-foxo3a-downregulation-by-epstein-barr-virus-encoded-lmp1-in-hodgkin-s-lymphoma
#20
Jun-Ichiro Ikeda, Naoki Wada, Satoshi Nojima, Shinichiro Tahara, Yoko Tsuruta, Kaori Oya, Eiichi Morii
Cancer-initiating cells (CICs) are specialized cells that have the ability to self-renew and are multipotent. We recently demonstrated that Forkhead box O3a (FoxO3a)-expressing cells exhibited a CIC-like potential in Hodgkin's lymphoma (HL). A proportion of HL patients are infected with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein (LMP) 1 downregulates FoxO3a, suggesting that FoxO3a expression may be abolished in EBV-positive HL. Inhibitors of DNA-binding (ID) proteins are highly conserved transcription factors mediating stem cell functions...
November 2016: Molecular and Clinical Oncology
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