scholarly journals A bacterial genotoxin causes virus reactivation and genomic instability in Epstein-Barr virus infected epithelial cells pointing to a role of co-infection in viral oncogenesis

2018 ◽  
Vol 144 (1) ◽  
pp. 98-109 ◽  
Author(s):  
Teresa Frisan ◽  
Noemi Nagy ◽  
Dimitrios Chioureas ◽  
Marie Terol ◽  
Francesca Grasso ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Genomic Instability ◽  
Epstein Barr Virus ◽  
Virus Reactivation ◽  
Viral Oncogenesis ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Epstein–Barr Virus DNase (BGLF5) induces genomic instability in human epithelial cells

2009 ◽  
Vol 38 (6) ◽  
pp. 1932-1949 ◽  
Author(s):  
Chung-Chun Wu ◽  
Ming-Tsan Liu ◽  
Yu-Ting Chang ◽  
Chih-Yeu Fang ◽  
Sheng-Ping Chou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Genomic Instability ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Human Epithelial Cells ◽  
Epstein Barr

scholarly journals Role of ATM in the Formation of the Replication Compartment during Lytic Replication of Epstein-Barr Virus in Nasopharyngeal Epithelial Cells

2014 ◽  
Vol 89 (1) ◽  
pp. 652-668 ◽  
Author(s):  
Pok Man Hau ◽  
Wen Deng ◽  
Lin Jia ◽  
Jie Yang ◽  
Tatsuya Tsurumi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Replication ◽  
Epstein Barr Virus ◽  
Viral Dna ◽  
Barr Virus ◽  
Lytic Reactivation ◽  
Infected Cells ◽  
Epstein Barr ◽  
Replication Compartment

ABSTRACTEpstein-Barr virus (EBV), a type of oncogenic herpesvirus, is associated with human malignancies. Previous studies have shown that lytic reactivation of EBV in latently infected cells induces an ATM-dependent DNA damage response (DDR). The involvement of ATM activation has been implicated in inducing viral lytic gene transcription to promote lytic reactivation. Its contribution to the formation of a replication compartment during lytic reactivation of EBV remains poorly defined. In this study, the role of ATM in viral DNA replication was investigated in EBV-infected nasopharyngeal epithelial cells. We observed that induction of lytic infection of EBV triggers ATM activation and localization of DDR proteins at the viral replication compartments. Suppression of ATM activity using a small interfering RNA (siRNA) approach or a specific chemical inhibitor profoundly suppressed replication of EBV DNA and production of infectious virions in EBV-infected cells induced to undergo lytic reactivation. We further showed that phosphorylation of Sp1 at the serine-101 residue is essential in promoting the accretion of EBV replication proteins at the replication compartment, which is crucial for replication of viral DNA. Knockdown of Sp1 expression by siRNA effectively suppressed the replication of viral DNA and localization of EBV replication proteins to the replication compartments. Our study supports an important role of ATM activation in lytic reactivation of EBV in epithelial cells, and phosphorylation of Sp1 is an essential process downstream of ATM activation involved in the formation of viral replication compartments. Our study revealed an essential role of the ATM-dependent DDR pathway in lytic reactivation of EBV, suggesting a potential antiviral replication strategy using specific DDR inhibitors.IMPORTANCEEpstein-Barr virus (EBV) is closely associated with human malignancies, including undifferentiated nasopharyngeal carcinoma (NPC), which has a high prevalence in southern China. EBV can establish either latent or lytic infection depending on the cellular context of infected host cells. Recent studies have highlighted the importance of the DNA damage response (DDR), a surveillance mechanism that evolves to maintain genome integrity, in regulating lytic EBV replication. However, the underlying molecular events are largely undefined. ATM is consistently activated in EBV-infected epithelial cells when they are induced to undergo lytic reactivation. Suppression of ATM inhibits replication of viral DNA. Furthermore, we observed that phosphorylation of Sp1 at the serine-101 residue, a downstream event of ATM activation, plays an essential role in the formation of viral replication compartments for replication of virus DNA. Our study provides new insights into the mechanism through which EBV utilizes the host cell machinery to promote replication of viral DNA upon lytic reactivation.

scholarly journals The role of the Epstein-Barr virus-encoded BARF1 gene expressed in human gastric epithelial cells

2020 ◽  
Vol 31 (11) ◽  
pp. 775-781
Author(s):  
Shuying Li ◽  
◽  
Fang Zhang ◽  
Ji Li ◽  
Xuya Hu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epstein Barr Virus ◽  
Gastric Epithelial Cells ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Differential Expression of the miR-200 Family MicroRNAs in Epithelial and B Cells and Regulation of Epstein-Barr Virus Reactivation by the miR-200 Family Member miR-429

2010 ◽  
Vol 84 (15) ◽  
pp. 7892-7897 ◽  
Author(s):  
Zhen Lin ◽  
Xia Wang ◽  
Claire Fewell ◽  
Jennifer Cameron ◽  
Qinyan Yin ◽  
...  
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Family Member ◽  
Epstein Barr Virus ◽  
Family Members ◽  
Receptor Activation ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

ABSTRACT The miR-200 microRNA family is important for maintaining the epithelial phenotype, partially through suppressing ZEB1 and ZEB2. Since ZEB1 inhibits Epstein-Barr virus (EBV) reactivation, we hypothesized that expression of miR-200 family members in epithelial cells may partly account for higher levels of EBV reactivation in this tissue (relative to nonplasma B cells). Here we show that, whereas miR-200 family members are expressed in epithelial cells, their expression is low in latently infected B cells. Furthermore, the miR-200 family member miR-429 shows elevated expression in plasma cell lines and is induced by B-cell-receptor activation in Akata cells. Lastly, expression of miR-429 can break latency.

Valganciclovir suppressed Epstein Barr virus reactivation during immunosuppression with alemtuzumab

2014 ◽  
Vol 59 (4) ◽  
pp. 255-258 ◽  
Author(s):  
Harinder Gill ◽  
Yu-Yan Hwang ◽  
Thomas S.Y. Chan ◽  
Annie W.K. Pang ◽  
Anskar Y.H. Leung ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

scholarly journals Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 285
Author(s):  
Xinle Cui ◽  
Zhouhong Cao ◽  
Yuriko Ishikawa ◽  
Sara Cui ◽  
Ken-Ichi Imadome ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
B Lymphocytes ◽  
Neutralizing Antibodies ◽  
Epstein Barr Virus ◽  
Lethal Dose ◽  
Envelope Proteins ◽  
Humanized Mice ◽  
Target Cells ◽  
Barr Virus ◽  
Epstein Barr

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.

scholarly journals Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 593
Author(s):  
Srikanth Umakanthan ◽  
Maryann M Bukelo
Keyword(s):  
Epstein Barr Virus ◽  
Diagnostic Tools ◽  
Main Role ◽  
Genetic Changes ◽  
Barr Virus ◽  
Cancer Pathogenesis ◽  
Genomic Studies ◽  
Epstein Barr ◽  
Oncogenic Form

Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.

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