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BZLF1

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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
#1
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 15, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28588024/bet-inhibitors-block-the-epstein-barr-virus-lytic-cycle-at-two-distinct-steps
#2
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...
June 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28456021/parp1-restricts-epstein-barr-virus-lytic-reactivation-by-binding-the-bzlf1-promoter
#3
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
#4
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...
February 28, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28228322/anti-tumour-research-of-recombinant-bcg-using-bzlf1-and-hgm-csf-fusion-genes
#5
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 (Gly4Ser)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
https://www.readbyqxmd.com/read/28179525/differentiation-dependent-lmp1-expression-is-required-for-efficient-lytic-epstein-barr-virus-reactivation-in-epithelial-cells
#6
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 that have latent infection, such as nasopharyngeal carcinoma (NPC), 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...
April 15, 2017: Journal of Virology
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/27595569/trichloromethane-fraction-of-incarvillea-compacta-induces-lytic-cytotoxicity-and-apoptosis-in-epstein-barr-virus-positive-gastric-cancer-ags-cells
#8
Lijing Zhang, Haifeng Wu, Guibo Sun, Xudong Xu, Xiaobo Sun, Li Cao
BACKGROUND: Incarvillea compacta Maxim. has been used to treat stomach disease in Tibet for many years. The objectives of this study were to explore the anti-cancer ability of trichloromethane fraction of I. compacta Maxim. roots (IC-TCL, R2) in EBV positive AGS cancer cells and its effects on cell cycle arrest, apoptosis and lytic induction. METHODS: MTT and trypan blue assays were to detect the inhibitory effects of different fraction in different cell lines. Hoechst 33342 staining, Annexin V-PE/7-AAD staining and DIOC6 staining were used to detect the apoptosis induction effects of R2...
September 5, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27430892/decitabine-inhibits-tumor-cell-proliferation-and-up-regulates-e-cadherin-expression-in-epstein-barr-virus-associated-gastric-cancer
#9
Munetaka Nakamura, Jun Nishikawa, Mari Saito, Kouhei Sakai, Sho Sasaki, Shinichi Hashimoto, Takeshi Okamoto, Yutaka Suehiro, Takahiro Yamasaki, Isao Sakaida
The present study investigated the effect of a DNA demethylating agent, decitabine, against Epstein-Barr virus-associated gastric cancer (EBVaGC). Decitabine inhibited cell growth and induced G2/M arrest and apoptosis in EBVaGC cell lines. The expression of E-cadherin was up-regulated and cell motility was significantly inhibited in the cells treated with decitabine. The promoter regions of p73 and RUNX3 were demethylated, and their expression was up-regulated by decitabine. They enhanced the transcription of p21, which induced G2/M arrest and apoptosis through down-regulation of c-Myc...
March 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/27430429/cytotoxic-effects-of-nf%C3%A2-%C3%AE%C2%BAb-inhibitors-in-combination-with-anti%C3%A2-herpes-agents-on-epstein%C3%A2-barr-virus%C3%A2-positive-gastric-carcinoma-in%C3%A2-vitro
#10
Paula Ordonez, Athira Nandakumar, Chihaya Koriyama, Megumi Yamomoto, Suminori Akiba
Epstein-Barr virus (EBV) infection in tumor cells is usually restricted to the latent form, indicating that the induction of viral lytic infection may present a novel approach for the treatment of EBV‑associated tumors. By contrast, EBV lytic replication is inhibited by high‑levels of nuclear factor (NF)‑κB, which suggests that NF‑κB inhibitors may activate lytic replication from the latent form. In the current study, the addition of NF‑κB inhibitors (Bay11‑7082, Z‑LLF‑CHO and aspirin) was observed to induce the EBV lytic genes BZLF1, BRLF1 and BMRF1 in EBV‑positive gastric cancer (GC) cells...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27334596/bzlf1-attenuates-transmission-of-inflammatory-paracrine-senescence-in-epstein-barr-virus-infected-cells-by-downregulating-tumor-necrosis-factor-alpha
#11
Xubing Long, Yuqing Li, Mengtian Yang, Lu Huang, Weijie Gong, Ersheng Kuang
UNLABELLED: Recent studies have shown that inflammatory responses trigger and transmit senescence to neighboring cells and activate the senescence-associated secretory phenotype (SASP). Latent Epstein-Barr virus (EBV) infection induces increased secretion of several inflammatory factors, whereas lytic infections evade the antiviral inflammatory response. However, the changes in and roles of the inflammatory microenvironment during the switch between EBV life cycles remain unknown. In the present study, we demonstrate that latent EBV infection in EBV-positive cells triggers the SASP in neighboring epithelial cells...
September 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27297582/lenalidomide-thalidomide-and-pomalidomide-reactivate-the-epstein-barr-virus-lytic-cycle-through-phosphoinositide-3-kinase-signaling-and-ikaros-expression
#12
Richard J Jones, Tawin Iempridee, Xiaobin Wang, Hans C Lee, Janet E Mertz, Shannon C Kenney, Heather C Lin, Veerabhadran Baladandayuthapani, Christopher W Dawson, Jatin J Shah, Donna M Weber, Robert Z Orlowski
PURPOSE: Lenalidomide, thalidomide, and pomalidomide (LTP) are immunomodulatory agents approved for use in multiple myeloma, but in some settings, especially with alkylating agents, an increase in Hodgkin lymphoma and other secondary primary malignancies (SPM) has been noted. Some of these malignancies have been linked to Epstein-Barr virus (EBV), raising the possibility that immunomodulatory drugs disrupt latent EBV infection. EXPERIMENTAL DESIGN: We studied the ability of LTP to reactivate latently infected EBV-positive cell lines in vitro and in vivo, and evaluated the EBV viral load in archived serum samples from patients who received a lenalidomide, thalidomide, and dexamethasone (LTD) combination...
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27297580/validation-of-an-ifn%C3%AE-il2-fluorospot-assay-for-clinical-trial-monitoring
#13
Nina Körber, Uta Behrends, Alexander Hapfelmeier, Ulrike Protzer, Tanja Bauer
BACKGROUND: The FluoroSpot assay, an advancement of the ELISpot assay, enables simultaneous measurement of different analytes secreted at a single-cell level. This allows parallel detection of several cytokines secreted by immune cells upon antigen recognition. Easier standardization, higher sensitivity and reduced labour intensity render FluoroSpot assays an interesting alternative to flow-cytometry based assays for analysis of clinical samples. While the use of immunoassays to study immunological primary and secondary endpoints becomes increasingly attractive, assays used require pre-trial validation...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27039668/epstein-barr-virus-reactivation-is-induced-but-abortive-in-cutaneous-lesions-of-systemic-hydroa-vacciniforme-and-hypersensitivity-to-mosquito-bites
#14
Takenobu Yamamoto, Yoji Hirai, Tomoko Miyake, Toshihisa Hamada, Osamu Yamasaki, Shin Morizane, Wataru Fujimoto, Keiji Iwatsuki
BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural killer (NK)-lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases are still unclear. OBJECTIVE: To understand the inflammatory process, we examined EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from patients with EBV-associated T/NK-LPDs. METHODS: Sixty-four patients with EBV-associated LPDs and epithelial neoplasms, and EBV+ cell line cells were studied...
June 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/26969667/comprehensive-profiling-of-ebv-gene-expression-in-nasopharyngeal-carcinoma-through-paired-end-transcriptome-sequencing
#15
Lijuan Hu, Zhirui Lin, Yanheng Wu, Juqin Dong, Bo Zhao, Yanbing Cheng, Peiyu Huang, Lihua Xu, Tianliang Xia, Dan Xiong, Hongbo Wang, Manzhi Li, Ling Guo, Elliott Kieff, Yixin Zeng, Qian Zhong, Musheng Zeng
The latent expression pattern of Epstein-Barr Virus (EBV) genes in nasopharyngeal carcinoma (NPC) has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type III latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through realtime PCR...
March 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/26933051/valpromide-inhibits-lytic-cycle-reactivation-of-epstein-barr-virus
#16
Kelly L Gorres, Derek Daigle, Sudharshan Mohanram, Grace E McInerney, Danielle E Lyons, George Miller
UNLABELLED: Reactivation of Epstein-Barr virus (EBV) from latency into the lytic phase of its life cycle allows the virus to spread among cells and between hosts. Valproic acid (VPA) inhibits initiation of the lytic cycle in EBV-infected B lymphoma cells. While VPA blocks viral lytic gene expression, it induces expression of many cellular genes, because it is a histone deacetylase (HDAC) inhibitor. Here we show, using derivatives of VPA, that blockade of EBV reactivation is separable from HDAC inhibition...
March 1, 2016: MBio
https://www.readbyqxmd.com/read/26663912/5-hydroxymethylation-of-the-ebv-genome-regulates-the-latent-to-lytic-switch
#17
Coral K Wille, Dhananjay M Nawandar, Amanda N Henning, Shidong Ma, Kayla M Oetting, Dennis Lee, Paul Lambert, Eric C Johannsen, Shannon C Kenney
Latent Epstein-Barr virus (EBV) infection and cellular hypermethylation are hallmarks of undifferentiated nasopharyngeal carcinoma (NPC). However, EBV infection of normal oral epithelial cells is confined to differentiated cells and is lytic. Here we demonstrate that the EBV genome can become 5-hydroxymethylated and that this DNA modification affects EBV lytic reactivation. We show that global 5-hydroxymethylcytosine (5hmC)-modified DNA accumulates during normal epithelial-cell differentiation, whereas EBV+ NPCs have little if any 5hmC-modified DNA...
December 29, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26653871/repression-of-ciita-by-the-epstein-barr-virus-transcription-factor-zta-is-independent-of-its-dimerization-and-dna-binding
#18
Nicolae Balan, Kay Osborn, Alison J Sinclair
Repression of the cellular CIITA gene is part of the immune evasion strategy of the γherpes virus Epstein-Barr virus (EBV) during its lytic replication cycle in B-cells. In part, this is mediated through downregulation of MHC class II gene expression via the targeted repression of CIITA, the cellular master regulator of MHC class II gene expression. This repression is achieved through a reduction in CIITA promoter activity, initiated by the EBV transcription and replication factor, Zta (BZLF1, EB1, ZEBRA)...
March 2016: Journal of General Virology
https://www.readbyqxmd.com/read/26581978/epstein-barr-virus-microrna-mir-bart20-5p-suppresses-lytic-induction-by-inhibiting-bad-mediated-caspase-3-dependent-apoptosis
#19
Hyoji Kim, Hoyun Choi, Suk Kyeong Lee
UNLABELLED: Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with a variety of tumor types. EBV can establish latency or undergo lytic replication in host cells. In general, EBV remains latent in tumors and expresses a limited repertoire of latent proteins to avoid host immune surveillance. When the lytic cycle is triggered by some as-yet-unknown form of stimulation, lytic gene expression and progeny virus production commence. Thus far, the exact mechanism of EBV latency maintenance and the in vivo triggering signal for lytic induction have yet to be elucidated...
February 2016: Journal of Virology
https://www.readbyqxmd.com/read/26560895/molecular-approach-to-targeted-therapy-for-multiple-sclerosis
#20
REVIEW
Gajanan V Sherbet
The development and evolution of targeted therapy to any disease require the identification of targets amenable to treatment of patients. Here the pathogenetic signalling systems involved in multiple sclerosis are scrutinised to locate nodes of deregulation and dysfunction in order to devise strategies of drug development for targeted intervention. Oliogoclonal bands (OCB) are isoelectric focusing profiles of immunoglobulins synthesised in the central nervous system. OCBs enable the diagnosis of multiple sclerosis with high sensitivity and specificity and are related to the course of the disease and progression...
2016: CNS & Neurological Disorders Drug Targets
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