scholarly journals Dynamic changes of cellular environment during Epstein-Barr virus productive replication

Uirusu ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 83-90
Author(s):  
Yoshitaka SATO
Keyword(s):  
Epstein Barr Virus ◽  
Dynamic Changes ◽  
Barr Virus ◽  
Cellular Environment ◽  
Epstein Barr ◽  
Productive Replication

scholarly journals Circulating Plasma Epstein–Barr virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Sha-sha He ◽  
Yun-ying Yang ◽  
Yan Wang ◽  
Yu-feng Ren ◽  
Cheng-tao Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Dynamic Changes ◽  
Barr Virus ◽  
Kaplan Meier ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Landmark Analyses ◽  
Predictive Indicator

Abstract PURPOSE Epstein Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma, while the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. METHODS We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan–Meier estimates. 12 and 24-month landmark analyses for OS data were performed according to the EBV groups. RESULTS Patients with post-EBV < 2,500 copies/mL achieved better survival than the higher ones. Furthermore, patients with continuously elevated EBV DNA had significantly poorer OS (HR: 2.542, 95%CI: 2.077–3.111, P < 0.001), DMFS (HR: 2.970, 95%CI: 2.392–3.687, P < 0.001), LRFS (HR: 1.699, 95%CI: 1.072–2.692, P = 0.013), and PFS (HR:2.535, 95%CI: 1.987–3.233, P < 0.001) than patients with continuously normal EBV or those with elevated levels at any time-point. The 5-year OS with elevated EBV was lower than the remission group by the 12 and 24-month landmark analysis. CONCLUSIONS Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis and unfavorable prognosis for NPC. In addition, EBV DNA was predictable no matter how long the follow-up time.

scholarly journals Transient increases in p53-responsible gene expression at early stages of Epstein-Barr virus productive replication

Cell Cycle ◽  
2010 ◽  
Vol 9 (4) ◽  
pp. 807-814 ◽  
Author(s):  
Yoshitaka Sato ◽  
Noriko Shirata ◽  
Takayuki Murata ◽  
Sho Nakasu ◽  
Ayumi Kudoh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Early Stages ◽  
Responsible Gene ◽  
Epstein Barr ◽  
Productive Replication

scholarly journals Epstein-Barr Virus Lytic Replication Elicits ATM Checkpoint Signal Transduction While Providing an S-phase-like Cellular Environment

2004 ◽  
Vol 280 (9) ◽  
pp. 8156-8163 ◽  
Author(s):  
Ayumi Kudoh ◽  
Masatoshi Fujita ◽  
Lumin Zhang ◽  
Noriko Shirata ◽  
Tohru Daikoku ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Epstein Barr Virus ◽  
S Phase ◽  
Lytic Replication ◽  
Barr Virus ◽  
Cellular Environment ◽  
Epstein Barr ◽  
Checkpoint Signal

scholarly journals Epstein-Barr Virus BGLF4 Kinase Induces Disassembly of the Nuclear Lamina To Facilitate Virion Production

2008 ◽  
Vol 82 (23) ◽  
pp. 11913-11926 ◽  
Author(s):  
Chung-Pei Lee ◽  
Yu-Hao Huang ◽  
Su-Fang Lin ◽  
Yao Chang ◽  
Yu-Hsin Chang ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Fluorescent Protein ◽  
Nuclear Lamina ◽  
Lamin A ◽  
Genome Replication ◽  
Barr Virus ◽  
Virion Production ◽  
Cellular Environment ◽  
Epstein Barr

ABSTRACT DNA viruses adopt various strategies to modulate the cellular environment for efficient genome replication and virion production. Previously, we demonstrated that the BGLF4 kinase of Epstein-Barr virus (EBV) induces premature chromosome condensation through the activation of condensin and topoisomerase IIα (C. P. Lee, J. Y. Chen, J. T. Wang, K. Kimura, A. Takemoto, C. C. Lu, and M. R. Chen, J. Virol. 81:5166-5180, 2007). In this study, we show that BGLF4 interacts with lamin A/C and phosphorylates lamin A protein in vitro. Using a green fluorescent protein (GFP)-lamin A system, we found that Ser-22, Ser-390, and Ser-392 of lamin A are important for the BGLF4-induced disassembly of the nuclear lamina and the EBV reactivation-mediated redistribution of nuclear lamin. Virion production and protein levels of two EBV primary envelope proteins, BFRF1 and BFLF2, were reduced significantly by the expression of GFP-lamin A(5A), which has five Ser residues replaced by Ala at amino acids 22, 390, 392, 652, and 657 of lamin A. Our data indicate that BGLF4 kinase phosphorylates lamin A/C to promote the reorganization of the nuclear lamina, which then may facilitate the interaction of BFRF1 and BFLF2s and subsequent virion maturation. UL kinases of alpha- and betaherpesviruses also induce the disassembly of the nuclear lamina through similar sites on lamin A/C, suggesting a conserved mechanism for the nuclear egress of herpesviruses.

Inhibition of productive replication of Epstein-Barr virus DNA by phosphonoacetic acid

Virology ◽  
1976 ◽  
Vol 71 (1) ◽  
pp. 352-354 ◽  
Author(s):  
Yoshihiro Yajima ◽  
Akiko Tanaka ◽  
Meihan Nonoyama
Keyword(s):  
Epstein Barr Virus ◽  
Phosphonoacetic Acid ◽  
Barr Virus ◽  
Epstein Barr ◽  
Productive Replication

scholarly journals Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF- B Signaling during Productive Replication

2013 ◽  
Vol 87 (7) ◽  
pp. 4060-4070 ◽  
Author(s):  
S. Saito ◽  
T. Murata ◽  
T. Kanda ◽  
H. Isomura ◽  
Y. Narita ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr ◽  
Productive Replication

scholarly journals Prevalence and significance of plasma Epstein-Barr Virus DNA level in nasopharyngeal carcinoma

2017 ◽  
Vol 58 (4) ◽  
pp. 509-516 ◽  
Author(s):  
Anussara Prayongrat ◽  
Chakkapong Chakkabat ◽  
Danita Kannarunimit ◽  
Pokrath Hansasuta ◽  
Chawalit Lertbutsayanukul
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Treatment Outcomes ◽  
Epstein Barr Virus ◽  
Locally Advanced ◽  
World Health ◽  
Disease Stage ◽  
Dynamic Changes ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV) DNA has been recognized as a promising tumor marker for nasopharyngeal carcinoma (NPC). This study aims to demonstrate the prevalence of plasma EBV DNA and its temporal correlation with treatment outcomes in the modern era. A total of 204 patients with Stage I–IVB NPC treated with intensity-modulated radiotherapy (IMRT) were enrolled. Quantitative plasma EBV DNA measurement was performed before treatment (pre-IMRT), on the fifth week of radiation (mid-IMRT), at 3 months after radiation (post-IMRT), then every 6 months until disease relapse. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Plasma EBV DNA was detected in 110 patients (53.9%), with a median pre-IMRT EBV DNA level of 8005 copies/ml. Significant correlation was noted between pre-IMRT EBV DNA level and disease stage, but not between pre-IMRT EBV DNA level and World Health Organization classification. With a median follow-up time of 35.1 months, the 3-year PFS and OS rates were higher in the group with undetectable pre-IMRT EBV DNA level compared with in the group in which it was detectable. When classified according to disease stage and pre-IMRT EBV DNA, patients with early disease and detectable pre-IMRT EBV DNA experienced poorer survival than those with locally advanced disease and undetectable pre-IMRT EBV DNA. According to the dynamic changes in EBV DNA level between pre-IMRT and mid/post IMRT, survival was significantly higher in patients who achieved an undetectable level following treatment. On multivariate analysis, post-IMRT EBV DNA level was the strongest predictor of all treatment outcomes (P &lt; 0.001). Our study demonstrated the clinical significance of the plasma EBV DNA level at specific time points, as well as of the dynamic changes in the EBV DNA level. Disappearance of plasma EBV DNA after treatment was associated with better survival.

scholarly journals Epstein-Barr Virus BGLF2 commandeers RISC to interfere with cellular miRNA function

2022 ◽  
Vol 18 (1) ◽  
pp. e1010235
Author(s):  
Ashley M. Campbell ◽  
Carlos F. De La Cruz Herrera ◽  
Edyta Marcon ◽  
Jack Greenblatt ◽  
Lori Frappier
Keyword(s):  
Epstein Barr Virus ◽  
Affinity Purification ◽  
Cell Types ◽  
Cellular Level ◽  
Processing Bodies ◽  
Barr Virus ◽  
Cytoplasmic Bodies ◽  
Cellular Environment ◽  
Multiple Cell ◽  
Epstein Barr

The Epstein-Barr virus (EBV) BGLF2 protein is a tegument protein with multiple effects on the cellular environment, including induction of SUMOylation of cellular proteins. Using affinity-purification coupled to mass-spectrometry, we identified the miRNA-Induced Silencing Complex (RISC), essential for miRNA function, as a top interactor of BGLF2. We confirmed BGLF2 interaction with the Ago2 and TNRC6 components of RISC in multiple cell lines and their co-localization in cytoplasmic bodies that also contain the stress granule marker G3BP1. In addition, BGLF2 expression led to the loss of processing bodies in multiple cell types, suggesting disruption of RISC function in mRNA regulation. Consistent with this observation, BGLF2 disrupted Ago2 association with multiple miRNAs. Using let-7 miRNAs as a model, we tested the hypothesis that BGLF2 interfered with the function of RISC in miRNA-mediated mRNA silencing. Using multiple reporter constructs with 3’UTRs containing let-7a regulated sites, we showed that BGLF2 inhibited let-7a miRNA activity dependent on these 3’UTRs, including those from SUMO transcripts which are known to be regulated by let-7 miRNAs. In keeping with these results, we showed that BGLF2 increased the cellular level of unconjugated SUMO proteins without affecting the level of SUMO transcripts. Such an increase in free SUMO is known to drive SUMOylation and would account for the effect of BGLF2 in inducing SUMOylation. We further showed that BGLF2 expression inhibited the loading of let-7 miRNAs into Ago2 proteins, and conversely, that lytic infection with EBV lacking BGLF2 resulted in increased interaction of let-7a and SUMO transcripts with Ago2, relative to WT EBV infection. Therefore, we have identified a novel role for BGLF2 as a miRNA regulator and shown that one outcome of this activity is the dysregulation of SUMO transcripts that leads to increased levels of free SUMO proteins and SUMOylation.

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