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https://www.readbyqxmd.com/read/29643934/extra-telomeric-functions-of-telomerase-in-the-pathogenesis-of-epstein-barr-virus-driven-b-cell-malignancies-and-potential-therapeutic-implications
#1
REVIEW
Silvia Giunco, Maria Raffaella Petrara, Manuela Zangrossi, Andrea Celeghin, Anita De Rossi
The Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus causally linked to a broad spectrum of both lymphoid and epithelial malignancies. In order to maintain its persistence in host cells and promote tumorigenesis, EBV must restrict its lytic cycle, which would ultimately lead to cell death, selectively express latent viral proteins, and establish an unlimited proliferative potential. The latter step depends on the maintenance of telomere length provided by telomerase. The viral oncoprotein LMP-1 activates TERT, the catalytic component of telomerase...
2018: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29599759/emergence-of-cd4-and-cd8-polyfunctional-t-cell-responses-against-immunodominant-lytic-and-latent-ebv-antigens-in-children-with-primary-ebv-infection
#2
Janice K P Lam, K F Hui, Raymond J Ning, X Q Xu, K H Chan, Alan K S Chiang
Long term carriers were shown to generate robust polyfunctional T cell (PFC) responses against lytic and latent antigens of Epstein-Barr virus (EBV). However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM]) and asymptomatic (AS) EBV infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29580369/mechanism-of-activation-of-the-bnlf2a-immune-evasion-gene-of-epstein-barr-virus-by-zta
#3
Rajaei Almohammed, Kay Osborn, Sharada Ramasubramanyan, Ijiel Barak Naranjo Perez-Fernandez, Anja Godfrey, Erika J Mancini, Alison J Sinclair
The human gamma herpes virus Epstein-Barr virus (EBV) exploits multiple routes to evade the cellular immune response. During the EBV lytic replication cycle, viral proteins are expressed that provide excellent targets for recognition by cytotoxic T cells. This is countered by the viral BNLF2a gene. In B cells during latency, where BNLF2a is not expressed, we show that its regulatory region is embedded in repressive chromatin. The expression of BNLF2a mirrors the expression of a viral lytic cycle transcriptional regulator, Zta (BZLF1, EB1, ZEBRA), in B cells and we propose that Zta plays a role in up-regulating BNLF2a...
March 26, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29529302/translational-profiling-of-b-cells-infected-with-the-epstein-barr-virus-reveals-5-leader-ribosome-recruitment-through-upstream-open-reading-frames
#4
Maja Bencun, Olaf Klinke, Agnes Hotz-Wagenblatt, Severina Klaus, Ming-Han Tsai, Remy Poirey, Henri-Jacques Delecluse
The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs...
February 26, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29522278/antitumor-effects-of-duvelisib-on-epstein-barr-virus-associated-lymphoma-cells
#5
Jun-Ichi Kawada, Shotaro Ando, Yuka Torii, Takahiro Watanabe, Yoshitaka Sato, Yoshinori Ito, Hiroshi Kimura
Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in EBV-associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV-associated lymphoma cell lines...
April 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29491233/characterization-of-in-vitro-expanded-virus-specific-t-cells-for-adoptive-immunotherapy-against-virus-infection
#6
Toshiaki Ono, Yuriko Fujita, Tetsuro Matano, Satoshi Takahashi, Tomohiro Morio, Ai Kawana-Tachikawa
Adoptive transfer of virus-specific T cells has emerged as a promising therapeutic approach for treatment of virus infections in immunocompromised hosts. Characterization of virus-specific T cells provides essential information about the curative mechanism of the treatment. In this study, we developed a T cell epitope mapping system for 718 overlapping peptides spanning 6 proteins of 3 viruses (pp65 and IE1 from cytomegalovirus; LMP1, EBNA1, and BZLF1 from Epstein-Barr virus; Penton from adenovirus). Peripheral blood mononuclear cells (PBMCs) from 33 healthy Japanese donors were stimulated with these peptides and virus-specific CD4+ and CD8+ T cells were expanded in vitro in the presence of interleukin (IL) 4 and IL7...
March 22, 2018: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29399111/-epigallocatechin-3-gallate-inhibition-of-epstein-barr-virus-spontaneous-lytic-infection-involves-downregulation-of-latent-membrane-protein-1
#7
Sufang Liu, Hongde Li, Min Tang, Ya Cao
The Epstein-Barr virus (EBV) lytic cycle contributes to the development of EBV-associated diseases. EBV-encoded latent membrane protein 1 (LMP1) is key to EBV lytic replication, and our previous work indicated that epigallocatechin-3-gallate (EGCG) inhibited constitutive EBV lytic infection through the suppression of LMP1-activated phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-related protein kinase 1/2 signaling. The present study demonstrated that LMP1 in CNE-LMP1 constructed cells significantly induced the expression of the EBV lytic proteins BZLF1 (P<0...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29394264/epstein-barr-virus-is-present-in-the-brain-of-most-cases-of-multiple-sclerosis-and-may-engage-more-than-just-b-cells
#8
Asma Hassani, John R Corboy, Suhail Al-Salam, Gulfaraz Khan
Multiple sclerosis (MS) is a chronic neuroinflammatory condition of the central nervous system (CNS). It is a major cause of neurological disability in young adults, particularly women. What triggers the destruction of myelin sheaths covering nerve fibres is unknown. Both genetic and infectious agents have been implicated. Of the infectious agents, Epstein-Barr virus (EBV), a common herpesvirus, has the strongest epidemiological and serological evidence. However, the presence of EBV in the CNS and demonstration of the underlying mechanism(s) linking EBV to the pathogenesis of MS remain to be elucidated...
2018: PloS One
https://www.readbyqxmd.com/read/29301829/identification-of-a-novel-ebv-based-antibody-risk-stratification-signature-for-early-detection-of-nasopharyngeal-carcinoma-in-taiwan
#9
Anna E Coghill, Ruth M Pfeiffer, Carla Proietti, Wan-Lun Hsu, Yin-Chu Chien, Lea Lekieffre, Lutz Krause, Andy Teng, Jocelyn Pablo, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Zhiwei Liu, Chien-Jen Chen, Jaap Middeldorp, Jason Mulvenna, Jeff Bethony, Allan Hildesheim, Denise L Doolan
Background Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. Methods We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29221139/epstein-barr-virus-in-tumor-infiltrating-b-cells-of-myasthenia-gravis-thymoma-an-innocent-bystander-or-an-autoimmunity-mediator
#10
Paola Cavalcante, Stefania Marcuzzo, Sara Franzi, Barbara Galbardi, Lorenzo Maggi, Teresio Motta, Raffaella Ghislandi, Antonella Buzzi, Luisella Spinelli, Lorenzo Novellino, Fulvio Baggi, Carlo Antozzi, Fabio Conforti, Tommaso Martino De Pas, Massimo Barberis, Pia Bernasconi, Renato Mantegazza
The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977893/combination-of-betulinic-acid-and-chidamide-synergistically-inhibits-epstein-barr-virus-replication-through-over-generation-of-reactive-oxygen-species
#11
Haibing Yu, Hongyu Zhang, Zhigang Chu, Qiongfang Ruan, Xueru Chen, Danli Kong, Xiaodong Huang, Huawen Li, Huanwen Tang, Hongjin Wu, Yifei Wang, Weiguo Xie, Yuanling Ding, Paul Yao
Epstein-Barr virus (EBV) has widely infected more than 90% of human populations. Currently, there is no efficient way to remove the virus because the EBV carriers are usually in a latent stage that allows them to escape the immune system and common antiviral drugs. In the effort to develop an efficient strategy for the removal of the EBV virus, we have shown that betulinic acid (BA) slightly suppresses EBV replication through SOD2 suppression with subsequent reactive oxygen species (ROS) generation and DNA damage in EBV-transformed LCL (lymphoblastoid cell line) cells...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874674/lytic-ebv-infection-investigated-by-detection-of-soluble-epstein-barr-virus-zebra-in-the-serum-of-patients-with-ptld
#12
Mohammed Habib, Marlyse Buisson, Julien Lupo, Felix Agbalika, Gérard Socié, Raphaele Germi, Monique Baccard, Berthe-Marie Imbert-Marcille, Jacques Dantal, Patrice Morand, Emmanuel Drouet
The ZEBRA protein (encoded by the BZLF1 gene), is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. Several studies highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders like post-transplant lymphoproliferative disease (PTLD). Here, we use an antigen-capture ELISA assay specifically designed to detecting the circulating soluble ZEBRA (sZEBRA) in serum samples (threshold value determined at 40ng/mL). We retrospectively investigated a population of 66 transplanted patients comprising 35 PTLD...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28707331/epstein-barr-virus-lytic-cycle-involvement-in-diffuse-large-b-cell-lymphoma
#13
Melina Cohen, Aldana Georgina Vistarop, Fuad Huaman, Marina Narbaitz, Fernanda Metrebian, Elena De Matteo, María Victoria Preciado, Paola Andrea Chabay
Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in diffuse large B cell lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina...
February 2018: Hematological Oncology
https://www.readbyqxmd.com/read/28675108/radiation-induced-epstein-barr-virus-reactivation-in-gastric-cancer-cells-with-latent-ebv-infection
#14
Athira Nandakumar, Futoshi Uwatoko, Megumi Yamamoto, Kazuo Tomita, Hideyuki J Majima, Suminori Akiba, Chihaya Koriyama
Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line)...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28666266/combination-of-betulinic-acid-and-chidamide-synergistically-inhibits-epstein-barr-virus-replication-through-over-generation-of-reactive-oxygen-species
#15
Haibing Yu, Hongyu Zhang, Zhigang Chu, Qiongfang Ruan, Xueru Chen, Danli Kong, Xiaodong Huang, Huawen Li, Huanwen Tang, Hongjin Wu, Yifei Wang, Weiguo Xie, Yuanling Ding, Paul Yao
Epstein-Barr virus (EBV) has widely infected more than 90% of human populations. Currently, there is no efficient way to remove the virus because the EBV carriers are usually in a latent stage that allows them to escape the immune system and common antiviral drugs. In the effort to develop an efficient strategy for the removal of the EBV virus, we have shown that betulinic acid (BA) slightly suppresses EBV replication through SOD2 suppression with subsequent reactive oxygen species (ROS) generation and DNA damage in EBV-transformed LCL (lymphoblastoid cell line) cells...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617871/hypoxia-inducible-factor-1%C3%AE-plays-roles-in-epstein-barr-virus-s-natural-life-cycle-and-tumorigenesis-by-inducing-lytic-infection-through-direct-binding-to-the-immediate-early-bzlf1-gene-promoter
#16
Richard J Kraus, Xianming Yu, Blue-Leaf A Cordes, Saraniya Sathiamoorthi, Tawin Iempridee, Dhananjay M Nawandar, Shidong Ma, James C Romero-Masters, Kyle G McChesney, Zhen Lin, Kathleen R Makielski, Denis L Lee, Paul F Lambert, Eric C Johannsen, Shannon C Kenney, Janet E Mertz
When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs). We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV). Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28588024/bromodomain-and-extraterminal-inhibitors-block-the-epstein-barr-virus-lytic-cycle-at-two-distinct-steps
#17
COMPARATIVE STUDY
Kristin M Keck, Stephanie A Moquin, Amanda He, Samantha G Fernandez, Jessica J Somberg, Stephanie M Liu, Delsy M Martinez, Jj L Miranda
Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. Proteins in the bromodomain and extraterminal (BET) family regulate multiple stages of viral life cycles and provide promising intervention targets. Synthetic small molecules can bind to the bromodomains and disrupt function by preventing recognition of acetylated lysine substrates. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV lytic cycle...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28456021/parp1-restricts-epstein-barr-virus-lytic-reactivation-by-binding-the-bzlf1-promoter
#18
Lena N Lupey-Green, Stephanie A Moquin, Kayla A Martin, Shane M McDevitt, Michael Hulse, Lisa B Caruso, Richard T Pomerantz, Jj L Miranda, Italo Tempera
The Epstein Barr virus (EBV) genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type, and in other herpesviruses, loss of CTCF binding at specific regions correlates with viral reactivation. Here, we demonstrate that binding of PARP1, an important cofactor of CTCF, at the BZLF1 lytic switch promoter restricts EBV reactivation. Knockdown of PARP1 in the Akata-EBV cell line significantly increases viral copy number and lytic protein expression...
July 2017: Virology
https://www.readbyqxmd.com/read/28257801/analysis-of-bzlf1-mrna-detection-in-saliva-as-a-marker-for-active-replication-of-epstein-barr-virus
#19
Ursula Fagin, Linda Nerbas, Bastian Vogl, Wolfram J Jabs
Monitoring replicative Epstein-Barr virus (EBV) infection still remains a challenge in modern laboratory routine. The immediate-early protein BZLF1 mediates the switch between latent and replicate forms of EBV infection. The aim of this study was to analyze the feasibility of BZLF1 mRNA detection in saliva as a marker for active replication of the virus. Various specimens (saliva, plasma, PBMC) from 17 patients with EBV-induced infectious mononucleosis (IM) and 4 control patients were examined for expression of viral BZLF1 mRNA by means of real-time PCR...
June 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28228322/anti-tumour-research-of-recombinant-bcg-using-bzlf1-and-hgm-csf-fusion-genes
#20
Qing-Jie Xue, Yun-Qing Li, Chun-Qing Yang, Ting Chen, Xiu-Zhen Li, Baohua Cheng, Chun-Mei Wang
The random primer Oligo(dT)15 was used in RT-PCR to obtain cDNA from the human granulocyte macrophage colony stimulating factor (hGM-CSF) gene and the Epstein-Barr virus (EBV) gene BZLF1. Then, the sequence splicing overlap extension method was used to obtain a GCBF fusion gene containing a linker sequence that encoded the polypeptide (Gly4 Ser)3 . The GCBF fusion gene was inserted into pMV261, which was then transformed into competent E. coli DH5 alpha cells, and positive cells were selected based on kanamycin resistance on LB plates...
March 14, 2017: Vaccine
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