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Latent membrane protein 1

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https://www.readbyqxmd.com/read/29352166/epstein-barr-virus-encoded-latent-membrane-protein-1-suppresses-necroptosis-through-targeting-ripk1-3-ubiquitination
#1
Xiaolan Liu, Yueshuo Li, Songling Peng, Xinfang Yu, Wei Li, Feng Shi, Xiangjian Luo, Min Tang, Zheqiong Tan, A M Bode, Ya Cao
Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29315015/tumor-specific-t-cells-engineered-to-overcome-tumor-immune-evasion-induce-clinical-responses-in-patients-with-relapsed-hodgkin-lymphoma
#2
Catherine M Bollard, Tamara Tripic, Conrad Russell Cruz, Gianpietro Dotti, Stephen Gottschalk, Vicky Torrano, Olga Dakhova, George Carrum, Carlos A Ramos, Hao Liu, Meng-Fen Wu, Andrea N Marcogliese, Cecilia Barese, Youli Zu, Daniel Y Lee, Owen O'Connor, Adrian P Gee, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney
Purpose Transforming growth factor-β (TGF-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) on the safety, survival, and activity of infused tumor-directed T cells. Materials and Methods In a dose escalation study, eight patients with Epstein Barr virus-positive Hodgkin lymphoma received two to 12 doses of between 2 × 107 and 1...
January 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29297744/tgfb1-is-secreted-through-an-unconventional-pathway-dependent-on-the-autophagic-machinery-and-cytoskeletal-regulators
#3
Julian Nüchel, Sushmita Ghatak, Alexandra V Zuk, Anja Illerhaus, Matthias Mörgelin, Katrin Schönborn, Katrin Blumbach, Sara A Wickström, Thomas Krieg, Gerhard Sengle, Markus Plomann, Beate Eckes
TGFB1 (transforming growth factor beta 1) is a potent cytokine playing a driving role in development, fibrosis and cancer. It is synthesized as prodomain-growth factor complex that requires tethering to LTBP (latent transforming growth factor beta binding protein) for efficient secretion into the extracellular space. Upon release, this large latent complex is sequestered by anchorage to extracellular matrix (ECM) networks, from which the mature growth factor needs to be activated in order to reach its receptors and initiate signaling...
January 3, 2018: Autophagy
https://www.readbyqxmd.com/read/29296923/the-oncogenic-membrane-protein-lmp1-sequesters-traf3-in-b-cell-lymphoma-cells-to-produce-functional-traf3-deficiency
#4
Pradeep Bangalore-Prakash, Laura L Stunz, Nurbek Mambetsariev, Amy L Whillock, Bruce S Hostager, Gail A Bishop
Loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (TRAF3) are commonly found in human B-cell malignancies, especially multiple myeloma and B-cell lymphoma (BCL). B-cell TRAF3 deficiency results in enhanced cell survival, elevated activation receptor signaling, and increased activity of certain transcriptional pathways regulating expression of prosurvival proteins. A recent analysis of TRAF3 protein staining of ∼300 human BCL tissue samples revealed that a higher proportion of samples expressing the oncogenic Epstein-Barr virus-encoded protein latent membrane protein 1 (LMP1) showed low/negative TRAF3 staining than predicted...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29247573/modulation-of-the-tumor-microenvironment-by-epstein-barr-virus-latent-membrane-protein-1-in-nasopharyngeal-carcinoma
#5
REVIEW
Tomokazu Yoshizaki, Satoru Kondo, Kazuhira Endo, Yosuke Nakanishi, Mitsuharu Aga, Eiji Kobayashi, Nobuyuki Hirai, Hisashi Sugimoto, Miyako Hatano, Takayoshi Ueno, Kazuya Ishikawa, Naohiro Wakisaka
Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors...
December 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29228057/n-acetylcysteine-nac-ameliorates-epstein-barr-virus-latent-membrane-protein-1-induced-chronic-inflammation
#6
Xiao Gao, Eirini-Maria Lampraki, Sarwah Al-Khalidi, Muhammad Asif Qureshi, Rhea Desai, Joanna Beatrice Wilson
Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions...
2017: PloS One
https://www.readbyqxmd.com/read/29213259/characterization-of-a-suppressive-cis-acting-element-in-the-epstein-barr-virus-lmp1-promoter
#7
Masahiro Yoshida, Takayuki Murata, Keiji Ashio, Yohei Narita, Takahiro Watanabe, H M Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura
Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein-Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29212935/tetraspanin-cd63-bridges-autophagic-and-endosomal-processes-to-regulate-exosomal-secretion-and-intracellular-signaling-of-epstein-barr-virus-lmp1
#8
Stephanie N Hurwitz, Mujeeb R Cheerathodi, Dingani Nkosi, Sara B York, David G Meckes
The tetraspanin protein CD63 has been recently described as a key factor in extracellular vesicle (EV) production and endosomal cargo sorting. In the context of Epstein-Barr virus (EBV) infection, CD63 is required for the efficient packaging of the major viral oncoprotein latent membrane protein 1 (LMP1) into exosomes and other EV populations, and acts as a negative regulator of LMP1 intracellular signaling. Accumulating evidence has also pointed to intersections of the endosomal and autophagy pathways in maintaining cellular secretory processes, and as sites for viral assembly and replication...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29202043/epstein-barr-virus-induces-adhesion-receptor-cd226-dnam-1-expression-during-primary-b-cell-transformation-into-lymphoblastoid-cell-lines
#9
Lisa Grossman, Chris Chang, Joanne Dai, Pavel A Nikitin, Dereje D Jima, Sandeep S Dave, Micah A Luftig
Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that mediate cell-cell adhesion. We report that EBV potently induced expression of the adhesion molecule CD226, which is not normally expressed on B cells. We found that early after infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein expression...
November 2017: MSphere
https://www.readbyqxmd.com/read/29188583/infusions-of-epstein-barr-virus-specific-cytotoxic-t-lymphocytes-as-post-remission-therapy-in-high-risk-post-transplant-lymphoproliferative-disorder-patients-report-of-two-cases
#10
Nayoun Kim, Hyun-Jung Sohn, Joo Hyun Oh, Young-Woo Jeon, Hyun-Joo Lee, Hyun-Il Cho, Byung Ha Chung, Chul-Woo Yang, Tai-Gyu Kim, Seok-Goo Cho
Conventional therapeutic approaches to post-transplant lymphoproliferative disorder (PTLD) occurring after solid-organ transplantation have shown only limited success in achieving durable response. Key factors driving the pathogenesis of PTLD include Epstein-Barr virus (EBV) reactivation and impaired immune surveillance due to prolonged immune suppression. Thus, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) have emerged as an alternative therapeutic approach for the treatment of EBV-associated PTLD by enhancing EBV-specific immunity...
November 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29145073/target-induced-proximity-ligation-triggers-recombinase-polymerase-amplification-and-transcription-mediated-amplification-to-detect-tumor-derived%C3%A2-exosomes-in-nasopharyngeal-carcinoma-with-high-sensitivity
#11
Wanli Liu, Jianpei Li, Yixian Wu, Shan Xing, Yanzhen Lai, Ge Zhang
Tumor-derived exosomes (TEXs) are extracellular vesicles that are continuously released into the blood by tumor cells and carry specific surface markers of the original tumor cells. Substantial evidence has implicated TEXs as attractive diagnostic markers for cancer. However, the detection of TEXs in blood at an early tumor stage is challenging due to their very low concentration. Here, we established a method called PLA-RPA-TMA assay that allows TEXs to be detected with high sensitivity and specificity. Based on two proximity ligation assay (PLA) probes that recognize a biomarker on a TEX, we generated a unique surrogate DNA signal for the specific biomarker, which was synchronously amplified twice by recombinase polymerase amplification (RPA) coupled with transcription-mediated amplification (TMA), and then the products of the RPA-TMA reaction were quantitatively detected using a gold nanoparticle-based colorimetric assay...
November 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29134204/latent-membrane-protein-1-is-a-novel-determinant-of-epstein-barr-virus-genome-persistence-and-reactivation
#12
Elizabeth A Caves, Rachel M Butch, Sarah A Cook, Laura R Wasil, Chen Chen, Yuanpu Peter Di, Nara Lee, Kathy H Y Shair
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that persistently infects humans, with nearly 95% seropositivity in adults. Infection in differentiating epithelia is permissive, but EBV-associated nasopharyngeal carcinoma (NPC) tumors harbor a clonal and nonproductive latent infection. However, in explanted NPC cultures and epithelial cell lines, episomal EBV genomes are frequently lost. The resulting unstable infection has hampered efforts to study the determinants of EBV persistence and latency in epithelial oncogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29118124/c-myc-represses-transcription-of-the-epstein-barr-virus-latent-membrane-protein-1-early-after-primary-b-cell-infection
#13
Alexander M Price, Joshua E Messinger, Micah A Luftig
Recent evidence has shown that the EBV oncogene LMP1 is not expressed at high levels early after EBV-infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased fifty-fold between seven days post infection and the LCL state. Metabolic labeling of nascently transcribed mRNA indicated this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28949981/mycobacterium-tuberculosis-reactivates-latent-hiv-1-in-t-cells-in-vitro
#14
Erica C Larson, Camille L Novis, Laura J Martins, Amanda B Macedo, Kadyn E Kimball, Alberto Bosque, Vicente Planelles, Louis R Barrows
Following proviral integration into the host cell genome and establishment of a latent state, the human immunodeficiency virus type 1 (HIV-1) can reenter a productive life cycle in response to various stimuli. HIV-1 reactivation occurs when transcription factors, such as nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFAT), and activator protein -1 (AP-1), bind cognate sites within the long terminal repeat (LTR) region of the HIV-1 provirus to promote transcription. Interestingly, pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) can reactivate latent HIV-1 through activation of the transcription factor NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28935569/constitutive-cd40-signaling-in-dendritic-cells-limits-atherosclerosis-by-provoking-inflammatory-bowel-disease-and-ensuing-cholesterol-malabsorption
#15
Pascal Kusters, Tom Seijkens, Christina Bürger, Bart Legein, Holger Winkels, Marion Gijbels, Christian Barthels, Remy Bennett, Linda Beckers, Dorothee Atzler, Erik Biessen, Thomas Brocker, Christian Weber, Norbert Gerdes, Esther Lutgens
The costimulatory molecule CD40 is a major driver of atherosclerosis. It is expressed on a wide variety of cell types, including mature dendritic cells (DCs), and is required for optimal T-cell activation and expansion. It remains undetermined whether and how CD40 on DCs impacts the pathogenesis of atherosclerosis. Here, the effects of constitutively active CD40 in DCs on atherosclerosis were examined using low-density lipoprotein-deficient (Ldlr(-/-)) bone marrow chimeras that express a transgene containing an engineered latent membrane protein 1 (LMP)/CD40 fusion protein conferring constitutive CD40 signaling under control of the DC-specific CD11c promoter (DC-LMP1/CD40)...
September 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28910387/epstein-barr-virus-latent-membrane-protein-1-enhances-dendritic-cell-therapy-lymph-node-migration-activation-and-il-12-secretion
#16
James M Termini, Sachin Gupta, Francesca N Raffa, Elizabeth Guirado, Margaret A Fischl, Liguo Niu, Saravana Kanagavelu, Geoffrey W Stone
Dendritic cells (DC) are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1) of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5) expressing LMP1 under the control of a Tet-inducible promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28881733/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#17
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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879169/herpes-simplex-virus-type-1-neuronal-infection-perturbs-golgi-apparatus-integrity-through-activation-of-src-tyrosine-kinase-and-dyn-2-gtpase
#18
Carolina Martin, Luis Leyton, Melissa Hott, Yennyfer Arancibia, Carlos Spichiger, Mark A McNiven, Felipe A Court, Margarita I Concha, Patricia V Burgos, Carola Otth
Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28878084/human-herpesvirus-8-interleukin-6-interacts-with-calnexin-cycle-components-and-promotes-protein-folding
#19
Daming Chen, Qiwang Xiang, John Nicholas
Viral interleukin-6 (vIL-6) encoded by human herpesvirus 8 (HHV-8) is believed to contribute via mitogenic, survival, and angiogenic activities to HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease through autocrine or paracrine mechanisms during latency or productive replication. There is direct evidence that vIL-6 promotes latently infected PEL cell viability and proliferation and also viral productive replication in PEL and endothelial cells. These activities are mediated largely through endoplasmic reticulum (ER)-localized vIL-6, which can induce signal transduction via the gp130 signaling receptor, activating mitogen-activated protein kinase and signal transducer and activator of transcription signaling, and interactions of vIL-6 with the ER membrane protein vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2)...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28859984/epstein-barr-virus-encoded-latent-membrane-protein-1-induces-epithelial-to-mesenchymal-transition-by-inducing-v-set-ig-domain-containing-4-vsig4-expression-via-nf-kb-in-renal-tubular-epithelial-hk-2%C3%A2-cells
#20
Seung-Mi Kim, Se Won Oh, Sang Hyun Park, Dae Young Hur, Seung-Woo Hong, Sang Youb Han
The epithelial to mesenchymal transition (EMT), a hallmark of chronic kidney disease, is a key event in the conversion from tubular epithelial cells to myofibroblasts in renal fibrosis. Epstein-Barr virus (EBV) is a γ-herpes oncovirus associated with chronic kidney disease. However, the relationship between EBV and the EMT process in renal tubular epithelial cells is not well understood. Among EBV-latent genes, EBV-encoded latent membrane protein 1 (LMP1) induces EMT by regulating a variety of molecules in EBV-induced oncogenic transformation...
October 21, 2017: Biochemical and Biophysical Research Communications
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