scholarly journals 12-O-Tetradecanoylphorbol-13-acetate Induces Epstein–Barr Virus Reactivation via NF-κB and AP-1 as Regulated by Protein Kinase C and Mitogen-Activated Protein Kinase

Virology ◽  
2001 ◽  
Vol 286 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Xiangrong Gao ◽  
Kazufumi Ikuta ◽  
Masako Tajima ◽  
Takeshi Sairenji
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Mitogen Activated Protein Kinase ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

scholarly journals Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

2015 ◽  
Vol 90 (2) ◽  
pp. 1129-1138 ◽  
Author(s):  
XueQiao Liu ◽  
Jeffrey I. Cohen
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Epstein Barr Virus ◽  
Virus Production ◽  
Mitogen Activated Protein Kinase ◽  
Tegument Protein ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Mitogen Activated Protein ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 and NF-κB promoter activity in AP-1– and NF-κB–luciferase reporter assays. We found that EBV BGLF2 activated AP-1 but not NF-κB reporter activity. Expression of EBV BGLF2 in cells activated p38 and c-Jun N-terminal kinase (JNK), both of which are important for mitogen-activated protein kinase (MAPK) signaling. Deletion of the carboxyl-terminal 66 amino acids of BGLF2 reduced the ability of BGLF2 to activate JNK and p38. Expression of BGLF2 enhanced BZLF1 expression in latently EBV-infected lymphoblastoid cell lines, and knockdown of BGLF2 reduced EBV reactivation induced by IgG cross-linking. Expression of BGLF2 induced BZLF1 expression and virus production in EBV-infected gastric carcinoma cells. BGLF2 enhanced BZLF1 expression and EBV production by activating p38; chemical inhibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production induced by BGLF2. In summary, the EBV tegument protein BGLF2, which is delivered to the cell at the onset of virus infection, activates the AP-1 pathway and enhances EBV reactivation and virus production.IMPORTANCEEpstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency.

scholarly journals Microtubule depolymerization activates the Epstein–Barr virus lytic cycle through protein kinase C pathways in nasopharyngeal carcinoma cells

2013 ◽  
Vol 94 (12) ◽  
pp. 2750-2758 ◽  
Author(s):  
Yi-Ru Liu ◽  
Sheng-Yen Huang ◽  
Jen-Yang Chen ◽  
Lily Hui-Ching Wang
Keyword(s):  
Protein Kinase C ◽  
Life Cycle ◽  
Protein Kinase ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr ◽  
In Cells

Elevated levels of antibodies against Epstein–Barr virus (EBV) and the presence of viral DNA in plasma are reliable biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC) in high-prevalence areas, such as South-East Asia. The presence of these viral markers in the circulation suggests that a minimal level of virus reactivation may have occurred in an infected individual, although the underlying mechanism of reactivation remains to be elucidated. Here, we showed that treatment with nocodazole, which provokes the depolymerization of microtubules, induces the expression of two EBV lytic cycle proteins, Zta and EA-D, in EBV-positive NPC cells. This effect was independent of mitotic arrest, as viral reactivation was not abolished in cells synchronized at interphase. Notably, the induction of Zta by nocodazole was mediated by transcriptional upregulation via protein kinase C (PKC). Pre-treatment with inhibitors for PKC or its downstream signalling partners p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) abolished the nocodazole-mediated induction of Zta and EA-D. Interestingly, the effect of nocodazole, as well as colchicine and vinblastine, on lytic gene expression occurred only in NPC epithelial cells but not in cells derived from lymphocytes. These results establish a novel role of microtubule integrity in controlling the EBV life cycle through PKC and its downstream pathways, which represents a tissue-specific mechanism for controlling the life-cycle switch of EBV.

scholarly journals The Epstein-Barr Virus-Encoded LMP2A and LMP2B Proteins Promote Epithelial Cell Spreading and Motility

2005 ◽  
Vol 79 (3) ◽  
pp. 1789-1802 ◽  
Author(s):  
Michael D. Allen ◽  
Lawrence S. Young ◽  
Christopher W. Dawson
Keyword(s):  
Protein Kinase ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tyrosine Kinases ◽  
Epstein Barr Virus ◽  
Cell Spreading ◽  
Mitogen Activated Protein Kinase ◽  
Barr Virus ◽  
Mitogen Activated Protein ◽  
Epstein Barr

ABSTRACT The frequent expression of latent membrane proteins LMP2A and LMP2B in Epstein Barr virus (EBV)-associated tumors suggests that these proteins play a role in EBV-induced epithelial cell growth transformation. Expression of LMP2A and LMP2B had no effect on the morphology of squamous epithelial cells in monolayer culture, but their expression was associated with an increased capacity to spread and migrate on extracellular matrix. Although the mechanisms by which LMP2A and LMP2B promote cell spreading and motility are unclear, the use of selective pharmacological inhibitors has established a role for tyrosine kinases in this phenotype but ruled out contributions of phosphatidylinositol 3-kinase, extracellular signal-regulated kinase/mitogen-activated protein kinase, and protein kinase C. The ability of LMP2B to induce a phenotype that is virtually indistinguishable from that of LMP2A suggests that regions of the LMP2 protein in addition to the cytosolic amino terminus are capable of inducing phenotypic effects in epithelial cells. Thus, rather than serving to modulate the activity of LMP2A, LMP2B may directly engage signaling pathways to influence epithelial cell behavior such as cell adhesion and motility.

Epstein-barr virus internalization and infectivity are blocked by selective protein kinase C inhibitors

1990 ◽  
Vol 45 (3) ◽  
pp. 490-493 ◽  
Author(s):  
Mara Cirone ◽  
Antonio Angeloni ◽  
Giuseppe Barile ◽  
Claudia Zompetta ◽  
Marco Venanzoni ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Protein Kinase C Inhibitors ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr

TPA induction of Epstein-Barr virus early antigens in Raji cells is blocked by selective protein kinase-C inhibitors

1987 ◽  
Vol 40 (6) ◽  
pp. 846-849 ◽  
Author(s):  
Janis Lazdins ◽  
Claudia Zompetta ◽  
Settimio Grimaldi ◽  
Giuseppe Barile ◽  
Marco Venanzoni ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Raji Cells ◽  
Protein Kinase C Inhibitors ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr
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