scholarly journals Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication

2009 ◽  
Vol 83 (23) ◽  
pp. 12108-12117 ◽  
Author(s):  
Fu-Zhang Wang ◽  
Debasmita Roy ◽  
Edward Gershburg ◽  
Christopher B. Whitehurst ◽  
Dirk P. Dittmer ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Expression Profiles ◽  
Nucleoside Analogs ◽  
Rna Expression ◽  
Viral Mrnas ◽  
Barr Virus ◽  
Reverse Transcription Pcr ◽  
Virus Transcription ◽  
Cell Culture Systems ◽  
Epstein Barr

ABSTRACT Although many drugs inhibit the replication of Epstein-Barr virus (EBV) in cell culture systems, there is still no drug that is effective and approved for use in primary EBV infection. More recently, maribavir (MBV), an l-ribofuranoside benzimidazole, has been shown to be a potent and nontoxic inhibitor of EBV replication and to have a mode of action quite distinct from that of acyclic nucleoside analogs such as acyclovir (ACV) that is based primarily on MBV's ability to block the phosphorylation of target proteins by EBV and human cytomegalovirus protein kinases. However, since the antiviral mechanisms of the drug are complex, we have carried out a comprehensive analysis of the effects of MBV on the RNA expression levels of all EBV genes with a quantitative real-time reverse transcription-PCR-based array. We show that in comparisons with ACV, the RNA expression profiles produced by the two drugs are entirely different, with MBV causing a pronounced inhibition of multiple viral mRNAs and with ACV causing virtually none. The results emphasize the different modes of action of the two drugs and suggest that the action of MBV may be linked to indirect effects on the transcription of EBV genes through the interaction of BGLF4 with multiple viral proteins.

scholarly journals Validation of Array‐based RNA Expression Profiles in Paraffin‐embedded Samples of Epstein‐Barr Virus‐related Malignancy

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Weihua Tang ◽  
Natalie Banet ◽  
Hind Muallem ◽  
Charles J Sailey ◽  
Zhiyuan Hu ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Expression Profiles ◽  
Rna Expression ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Modulation of Enhancer Looping and Differential Gene Targeting by Epstein-Barr Virus Transcription Factors Directs Cellular Reprogramming

2013 ◽  
Vol 9 (9) ◽  
pp. e1003636 ◽  
Author(s):  
Michael J. McClellan ◽  
C. David Wood ◽  
Opeoluwa Ojeniyi ◽  
Tim J. Cooper ◽  
Aditi Kanhere ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Targeting ◽  
Epstein Barr Virus ◽  
Cellular Reprogramming ◽  
Barr Virus ◽  
Virus Transcription ◽  
Differential Gene ◽  
Epstein Barr

scholarly journals Protein Kinase CK2 Phosphorylation of EB2 Regulates Its Function in the Production of Epstein-Barr Virus Infectious Viral Particles

2007 ◽  
Vol 81 (21) ◽  
pp. 11850-11860 ◽  
Author(s):  
Cahora Medina-Palazon ◽  
Henri Gruffat ◽  
Fabrice Mure ◽  
Odile Filhol ◽  
Valérie Vingtdeux-Didier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nuclear Export ◽  
Epstein Barr Virus ◽  
Nuclear Export Signal ◽  
Regulatory Subunit ◽  
Viral Mrnas ◽  
Barr Virus ◽  
Early Protein ◽  
Epstein Barr

ABSTRACT The Epstein-Barr Virus (EBV) early protein EB2 (also called BMLF1, Mta, or SM) promotes the nuclear export of a subset of early and late viral mRNAs and is essential for the production of infectious virions. We show here that in vitro, protein kinase CK2α and -β subunits bind both individually and, more efficiently, as a complex to the EB2 N terminus and that the CK2β regulatory subunit also interacts with the EB2 C terminus. Immunoprecipitated EB2 has CK2 activity that phosphorylates several sites within the 80 N-terminal amino acids of EB2, including Ser-55, -56, and -57, which are localized next to the nuclear export signal. EB2S3E, the phosphorylation-mimicking mutant of EB2 at these three serines, but not the phosphorylation ablation mutant EB2S3A, efficiently rescued the production of infectious EBV particles by HEK293BMLF1-KO cells harboring an EB2-defective EBV genome. The defect of EB2S3A in transcomplementing 293BMLF1-KO cells was not due to impaired nucleocytoplasmic shuttling of the mutated protein but was associated with a decrease in the cytoplasmic accumulation of several late viral mRNAs. Thus, EB2-mediated production of infectious EBV virions is regulated by CK2 phosphorylation at one or more of the serine residues Ser-55, -56, and -57.

Imaging and therapy for Epstein-Barr virus-associated gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4644-4644
Author(s):  
D. Fu ◽  
J. Chong ◽  
C. Foss ◽  
J. Fox ◽  
S. Wang ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Tumor Regression ◽  
Human Cancer ◽  
Nucleoside Analogs ◽  
Scid Mice ◽  
Tumor Xenografts ◽  
Barr Virus ◽  
Bortezomib Treatment ◽  
Epstein Barr

4644 Background: Epstein-Barr virus (EBV) has been identified in a wide variety of malignancies, including gastric carcinomas. The virus encodes kinases that phosphorylate nucleoside analogs such as 2’-deoxy-2’-fluoro-5-iodo-1-beta-D- arabinofuranosyluracil (FIAU). We hypothesized that it might be possible to use the viral enzyme to specifically concentrate [125I]FIAU or [131I] FIAU in tumor cells harboring virus and thus deliver imaging and therapeutic radiation. Bortezomib is a potent stimulator of viral kinase expression in EBV tumor cell lines. Methods: We imaged lytic induction in vivo and evaluated the effect of [131I] FIAU on human cancer xenografts in SCID mice. These include a tumor line engineered to constitutively express the EBV thymide kinase (EBVTK), and a control engineered with a sham vector (SHAM), as well one EBV-associated human gastric tumor (KT tumor). Mice were treated with buffer, bortezomib (2μg/g), or radiolabeled FIAU or radiolabeled FIAU and bortezomib in combination. For imaging, mice, [125I]-FIAU and SPECT/CT were used. For therapy, 131I-FIAU was used and tumor dimensions were monitored with calipers. Results: SPECT/CT imaging with [125I]-FIAU of tumor-bearing SCID mice showed selective concentration of radiotracer in tumor tissue in EBVTK (3/3) and in EBV-associated KT tumors (3/3) when animals were pretreated with bortezomib. Treatment with buffer had no effect on 3 EBVTK tumors and 3 SHAM tumors all of which increased in volume. Treatment with 1.6 mCi of [131I]-FIAU alone led to tumor response in 3/3 mice with EBVTK tumors and 0/3 mice with SHAM tumors. Treatment with [131I]-FIAU alone had no effect on EBV KT tumor xenografts (0/3) and all tumors increased in volume. Treatment with bortezomib induced modest responses in all KT tumors. However, treatment with bortezomib and [131I]-FIAU led to marked tumor regression (>80%) in EBV-associated KT tumors (3/3). Conclusions: Treatment with bortezomib leads to selective concentration of radiolabeled FIAU in the EBV-associated tumor xenografts. In combination with [131I]-FIAU it leads to tumor regression. No significant financial relationships to disclose.

scholarly journals Maribavir Inhibits Epstein-Barr Virus Transcription through the EBV Protein Kinase

2013 ◽  
Vol 87 (9) ◽  
pp. 5311-5315 ◽  
Author(s):  
C. B. Whitehurst ◽  
M. K. Sanders ◽  
M. Law ◽  
F.-Z. Wang ◽  
J. Xiong ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Virus Transcription ◽  
Epstein Barr

scholarly journals An Epstein-Barr virus transcription unit is at least 84 kilobases long

1986 ◽  
Vol 14 (6) ◽  
pp. 2611-2620 ◽  
Author(s):  
Myriam Bodescot ◽  
Olivier Brison ◽  
Michel Perricaudet
Keyword(s):  
Epstein Barr Virus ◽  
Transcription Unit ◽  
Barr Virus ◽  
Virus Transcription ◽  
Epstein Barr

scholarly journals Epstein-Barr Virus Transcription Activator R Upregulates BARF1 Expression by Direct Binding to Its Promoter, Independent of Methylation

2012 ◽  
Vol 86 (20) ◽  
pp. 11322-11332 ◽  
Author(s):  
E. K. Hoebe ◽  
C. Wille ◽  
E. S. Hopmans ◽  
A. R. Robinson ◽  
J. M. Middeldorp ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Transcription Activator ◽  
Barr Virus ◽  
Virus Transcription ◽  
Direct Binding ◽  
Epstein Barr

scholarly journals Analysis of Epstein-Barr Virus Genomes and Expression Profiles in Gastric Adenocarcinoma

2017 ◽  
Vol 92 (2) ◽  
Author(s):  
Ivan Borozan ◽  
Marc Zapatka ◽  
Lori Frappier ◽  
Vincent Ferretti
Keyword(s):  
Epstein Barr Virus ◽  
Expression Profiles ◽  
Whole Genome Sequence ◽  
Small Subset ◽  
Whole Genome ◽  
Genome Sequences ◽  
Sequence Comparisons ◽  
Barr Virus ◽  
Epstein Barr ◽  
Virus Genomes

ABSTRACTEpstein-Barr virus (EBV) is a causative agent of a variety of lymphomas, nasopharyngeal carcinoma (NPC), and ∼9% of gastric carcinomas (GCs). An important question is whether particular EBV variants are more oncogenic than others, but conclusions are currently hampered by the lack of sequenced EBV genomes. Here, we contribute to this question by mining whole-genome sequences of 201 GCs to identify 13 EBV-positive GCs and by assembling 13 new EBV genome sequences, almost doubling the number of available GC-derived EBV genome sequences and providing the first non-Asian EBV genome sequences from GC. Whole-genome sequence comparisons of all EBV isolates sequenced to date (85 from tumors and 57 from healthy individuals) showed that most GC and NPC EBV isolates were closely related although American Caucasian GC samples were more distant, suggesting a geographical component. However, EBV GC isolates were found to contain some consistent changes in protein sequences regardless of geographical origin. In addition, transcriptome data available for eight of the EBV-positive GCs were analyzed to determine which EBV genes are expressed in GC. In addition to the expected latency proteins (EBNA1, LMP1, and LMP2A), specific subsets of lytic genes were consistently expressed that did not reflect a typical lytic or abortive lytic infection, suggesting a novel mechanism of EBV gene regulation in the context of GC. These results are consistent with a model in which a combination of specific latent and lytic EBV proteins promotes tumorigenesis.IMPORTANCEEpstein-Barr virus (EBV) is a widespread virus that causes cancer, including gastric carcinoma (GC), in a small subset of individuals. An important question is whether particular EBV variants are more cancer associated than others, but more EBV sequences are required to address this question. Here, we have generated 13 new EBV genome sequences from GC, almost doubling the number of EBV sequences from GC isolates and providing the first EBV sequences from non-Asian GC. We further identify sequence changes in some EBV proteins common to GC isolates. In addition, gene expression analysis of eight of the EBV-positive GCs showed consistent expression of both the expected latency proteins and a subset of lytic proteins that was not consistent with typical lytic or abortive lytic expression. These results suggest that novel mechanisms activate expression of some EBV lytic proteins and that their expression may contribute to oncogenesis.

Sign in / Sign up

Export Citation Format

Share Document