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https://www.readbyqxmd.com/read/27903798/lubac-modulates-lmp1-activation-of-nf%C3%AE%C2%BAb-and-irf7
#1
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 NFκB in different biological contexts. However, the role of LUBAC in LMP1 signaling leading to NFκB and IRF7 activation has not been investigated. We have shown here that RNF31, the key component of LUBAC complex, interacts with LMP1 and IRF7 in EBV-transformed cells, and that LUBAC stimualtes linear ubiquitination of NEMO and IRF7. Consequently, LUBAC is required for LMP1 signaling to full activation of NFκB, but inhibits LMP1-stimulated IRF7 transcriptional activity...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27900085/id1-upregulation-and-foxo3a-downregulation-by-epstein-barr-virus-encoded-lmp1-in-hodgkin-s-lymphoma
#2
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
https://www.readbyqxmd.com/read/27873282/ebv-directed-t-cell-therapeutics-for-ebv-associated-lymphomas
#3
Lauren P McLaughlin, Stephen Gottschalk, Cliona M Rooney, Catherine M Bollard
Epstein Barr virus (EBV) is a human gamma herpes virus that establishes latency in B cells after primary infection. EBV generally only causes a mild, self-limiting viral illness but is also associated with several malignancies including posttransplantation lymphoproliferative disorder in the immunosuppressed host as well as Hodgkin and non-Hodgkin lymphoma in the immune competent host. The expression of EBV antigens by lymphoma has important applications as targets for adoptive T cell therapy. However, as many lymphomas only express subdominant EBV antigens that are less immunogenic, novel strategies are needed to manufacture EBV-specific T cell products specific for Latent Membrane Protein 1 (LMP1) and LMP2, which are expressed in lymphomas with type II and III latency...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27873269/the-use-of-3d-telomere-fish-for-the-characterization-of-the-nuclear-architecture-in-ebv-positive-hodgkin-s-lymphoma
#4
Hans Knecht, Sabine Mai
The 3D nuclear architecture is closely related to cellular functions and chromosomes are organized in distinct territories. Quantitative 3D telomere FISH analysis (3D Q-FISH) and 3D super-resolution imaging (3D-SIM) at a resolution up to 80 nm as well as the recently developed combined quantitative 3D TRF2-telomere immune FISH technique (3D TRF2/Telo-Q-FISH) have substantially contributed to elucidate molecular pathogenic mechanisms of hematological diseases. Here we report the methods we applied to uncover major molecular steps involved in the pathogenesis of EBV-associated Hodgkin's lymphoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27856754/mouse-model-for-acute-epstein-barr-virus-infection
#5
Tristan Wirtz, Timm Weber, Sven Kracker, Thomas Sommermann, Klaus Rajewsky, Tomoharu Yasuda
Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27819673/lmp1-signaling-pathway-activates-irf4-in-latent-ebv-infection-and-a-positive-circuit-between-pi3k-and-src-is-required
#6
L Wang, J Ren, G Li, J P Moorman, Z Q Yao, S Ning
Interferon (IFN) regulatory factors (IRFs) have crucial roles in immune regulation and oncogenesis. We have recently shown that IRF4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. However, the intracellular signaling pathway triggering Src activation of IRF4 remains unknown. In this study, we provide evidence that Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promotes IRF4 phosphorylation and markedly stimulates IRF4 transcriptional activity, and that Src mediates LMP1 activation of IRF4...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27813134/establishment-and-characterization-of-a-novel-hodgkin-lymphoma-cell-line-am-hlh-carrying-the-epstein-barr-virus-genome-integrated-into-the-host-chromosome
#7
Masahiko Hayashida, Masanori Daibata, Erika Tagami, Takahiro Taguchi, Fumiyo Maekawa, Kayo Takeoka, Katsuhiro Fukutsuka, Daiki Shimomura, Takamasa Hayashi, Yoshinori Iwatani, Hitoshi Ohno
We describe the establishment and characterization of a cell line, AM-HLH, obtained from a patient with Epstein-Barr virus-positive (EBV(+) ) nodular sclerosis-type Hodgkin lymphoma (HL). The cells were positive for CD2 and CD30 and negative for CD15. The immunoglobulin heavy- and κ light-chain genes were rearranged. The karyotype was of the triploid range. Southern blotting using the EBV terminal repeat probe detected 3 hybridizing bands that were identical to those of the parental HL material. The cells expressed EBV-encoded RNAs as well as latent genes (EBNA1, EBNA2, LMP1, and LMP2A) and lytic genes (BZLF1 and BALF2)...
November 4, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27793268/spontaneous-metastases-in-immunocompetent-mice-harboring-a-primary-tumor-driven-by-oncogene-latent-membrane-protein-1-from-epstein-barr-virus
#8
Pu-Yuan Chang, Yenlin Huang, Tzu-Yuan Hung, Kowit-Yu Chong, Yu-Sun Chang, Chuck C-K Chao, Kai-Ping N Chow
BACKGROUND: In vitro and clinical studies suggest that the oncogene LMP1 (latent membrane protein 1) encoded by Epstein-Barr virus (EBV) plays a role in the development of nasopharyngeal carcinoma (NPC) and the formation of metastases in immunocompetent individuals. However, whether LMP1 itself is sufficient to drive these events in immunocompetent hosts remains elusive due to the lack of appropriate experimental models. The aim of this study was to study LMP1-dependent tumorigenesis and metastasis in BALB/c mice inoculated with BALB/c-3T3 cells expressing N-LMP1 (a Taiwanese NPC variant)...
August 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27737703/pd-l1-is-upregulated-by-ebv-driven-lmp1-through-nf-%C3%AE%C2%BAb-pathway-and-correlates-with-poor-prognosis-in-natural-killer-t-cell-lymphoma
#9
Xi-Wen Bi, Hua Wang, Wen-Wen Zhang, Jing-Hua Wang, Wen-Jian Liu, Zhong-Jun Xia, Hui-Qiang Huang, Wen-Qi Jiang, Yu-Jing Zhang, Liang Wang
BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated. METHODS: Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively...
October 13, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27732937/tofacitinib-induces-g1-cell-cycle-arrest-and-inhibits-tumor-growth-in-epstein-barr-virus-associated-t-and-natural-killer-cell-lymphoma-cells
#10
Shotaro Ando, Jun-Ichi Kawada, Takahiro Watanabe, Michio Suzuki, Yoshitaka Sato, Yuka Torii, Masato Asai, Fumi Goshima, Takayuki Murata, Norio Shimizu, Yoshinori Ito, Hiroshi Kimura
Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27686857/ganetespib-an-hsp90-inhibitor-kills-epstein-barr-virus-ebv-infected-b-and-t-cells-and-reduces-the-percentage-of-ebv-infected-cells-in-the-blood
#11
Amber Shatzer, Mir A Ali, Mayra Chavez, Kennichi Dowdell, Min-Jung Lee, Yusuke Tomita, Iman El-Hariry, Jane B Trepel, David A Proia, Jeffrey I Cohen
HSP90 inhibitors have been shown to kill Epstein-Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells with ganetespib, an HSP90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed EBV-positive B and T cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV-positive lymphomas and prolonged survival in SCID mice inoculated with one EBV-transformed B-cell line, but not another B-cell line...
August 11, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27677953/epstein-barr-virus-associated-gastric-cancer-and-potential-mechanisms-of-oncogenesis
#12
Ezequiel M Fuentes-Pananá, Abigail Morales-Sánchez
EBV-associated Gastric Cancer (EBVaGC) comprises about 9% of all cases of GC and constitutes a distinct clinicopathological and molecular entity. The pattern of viral expression in EBVaGC cannot be set to any of the previously EBV-associated malignancies. Several lines of evidence support that viral expression in EBVaGC is characterized by high transcription of the BamH1-A rightward transcript (BART), low-levels of EBNA-1 and lack of LMP1. The high transcription activity of the BamH1-A region is importantly directed to express BART miRNAs, supporting a critical role for these miRNAs during epithelial cell infection and carcinogenesis...
September 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27668971/serum-b-cell-activating-factor-predicts-prognosis-in-nasal-type-extranodal-nk-t-cell-lymphoma
#13
Li Zhang, Na Li, Li Yang, Jing Zhang, Hua-Wei Weng, Li-Qun Zou
B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells...
December 2016: Cytokine
https://www.readbyqxmd.com/read/27650372/phage-display-screening-identifies-lmp1-binding-peptides-targeting-the-c-terminus-region-of-the-ebv-oncoprotein
#14
Nihel Ammous-Boukhris, Amor Mosbah, Emna Sahli, Wajdi Ayadi, Boutheina Hadhri-Guiga, Ameur Chérif, Ali Gargouri, Raja Mokdad-Gargouri
Latent membrane protein 1 (LMP1), a major oncoprotein of Epstein Barr Virus (EBV) is responsible for transforming B lymphocytes in vitro. LMP1 is overexpressed in several EBV-associated malignancies, and different approaches have been developed to reduce its level and accordingly its oncogenic function in tumor tissues. This study aimed to use phage display peptide library to obtain peptides which could specifically bind to the cytoplasmic region of LMP1 to prevent its interaction with signaling proteins. The LMP1 C-terminus region was produced in bacterial E...
September 17, 2016: Peptides
https://www.readbyqxmd.com/read/27632954/epstein-barr-virus-latent-membrane-protein-1-up-regulates-cytokines-and-correlates-with-older-age-and-poorer-prognosis-in-hodgkin-lymphoma
#15
Kung-Chao Chang, Paul C-H Chen, Yao Chang, Yu-Hsuan Wu, Ya-Ping Chen, Chien-Hsien Lai, L Jeffrey Medeiros, Ih-Jen Su, Hsei-Wei Wang
AIMS: Previously, we reported an association between Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL), older age, and poorer prognosis. The aim of this study was to investigate the mechanisms underlying this association. METHODS AND RESULTS: Transfection of HL cell lines with EBV latent membrane protein-1 (LMP1) resulted in up-regulation of many cytokine genes as assessed by the use of oligonucleotide microarrays. The up-regulation of cytokines was validated by using an inflammatory cytokine protein array: macrophage inflammatory protein (MIP)-1α, MIP-1β, and interleukin (IL)-13...
September 16, 2016: Histopathology
https://www.readbyqxmd.com/read/27631517/ebv-negative-aggressive-nk-cell-leukemia-lymphoma-clinical-pathologic-and-genetic-features
#16
Alina Nicolae, Karthik A Ganapathi, Trinh Hoc-Tran Pham, Liqiang Xi, Carlos A Torres-Cabala, Nahid M Nanaji, Hongbin D Zha, Zhen Fan, Sybil Irwin, Stefania Pittaluga, Mark Raffeld, Elaine S Jaffe
Aggressive natural killer cell leukemia (ANKL) is a systemic NK-cell neoplasm, almost always associated with Epstein-Barr virus (EBV). Rare cases of EBV-negative ANKL have been described, and some reports suggested more indolent behavior. We report the clinicopathologic, immunophenotypic, and molecular characteristics of 7 EBV-negative ANKL. All patients were adults, with a median age of 63 years (range 22 to 83 y) and an M:F ratio of 2.5:1. Five patients were White, 1 Black, and 1 Asian. All patients presented acutely, with fever (6/7), cytopenias (6/7), and splenomegaly (4/7)...
September 14, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27600027/epstein-barr-virus-mrna-profiles-and-viral-dna-methylation-status-in-nasopharyngeal-brushings-from-nasopharyngeal-carcinoma-patients-reflect-tumor-origin
#17
Octavia Ramayanti, Hedy Juwana, Sandra A M W Verkuijlen, Marlinda Adham, Michiel D Pegtel, Astrid E Greijer, Jaap M Middeldorp
Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load and RNA transcripts in nasopharyngeal (NP) brushings is useful for minimally invasive NPC diagnosis. However, whether these EBV markers relate to local virus replication or reflect tumor origin remains to be demonstrated. To resolve this, we analysed EBV-DNA characteristics and quantified latent and lytic viral RNA transcripts in NP brushings and matching frozen NP-biopsy specimens from patients suspected of having NPC...
January 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27567526/positive-regulation-of-hif-1a-expression-by-ebv-oncoprotein-lmp1-in-nasopharyngeal-carcinoma-cells
#18
Wei-Wen Sung, Yi-Chih Chu, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a pivotal viral oncoprotein that contributes to the carcinogenesis of Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC). We investigated the regulation of hypoxia-inducible factor 1-α (HIF-1α) by LMP1. In NPC cells, we found that LMP1 significantly enhanced the HIF-1α mRNA level, and not only the protein amount as described previously. Mechanistically, the stability of the HIF-1α transcript was remarkably prolonged by LMP1 via reduced expressions of RNA-destabilizing proteins tristetraprolin (TTP) and pumilio RNA-binding family member 2 (PUM2) through C-terminal activation region 1 (CTAR1) and CTAR3 interaction with the ERK1/2 and STAT3 signaling pathways, respectively, in parallel with hindrance of PUM2 binding to the HIF-1α mRNA 3'-untranslated region (3'-UTR)...
November 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27543511/undifferentiated-nasopharyngeal-carcinoma-mimicking-hodgkin-lymphoma-with-cd30-expression
#19
Mark N Jabbour, Samer Nassif, Zaher Chakhachiro
The presence of CD30-expressing Hodgkin-like cells with a background of inflammation and eosinophils in a young adolescent is usually diagnostic of classical Hodgkin lymphoma. Herein we present the case of a 12-year-old boy presenting with enlarged cervical lymph node characterized by the presence of Hodgkin-like cells expressing CD30 and EBV-LMP1 with a Hodgkin-like background. The Hodgkin-like cells were negative for CD15, CD20, CD45, and Pax-5. The tumor cells, however, expressed several cytokeratins, confirming the diagnosis of an undifferentiated carcinoma nasopharyngeal type...
August 19, 2016: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27509984/expression-of-epstein-barr-virus-encoded-ebna1-and-lmp1-oncoproteins-in-nasopharyngeal-carcinomas-from-northeast-india
#20
Parikhit Borthakur, Kangkana Kataki, Chenole Keppen, V Khamo, Subhash Medhi, Manab Deka
BACKGROUND: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin. OBJECTIVES: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
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