scholarly journals Induction of the Early Growth Response 1 Gene by Epstein-Barr Virus Lytic Transactivator Zta

2006 ◽  
Vol 80 (15) ◽  
pp. 7748-7755 ◽  
Author(s):  
Yao Chang ◽  
Heng-Huan Lee ◽  
Yu-Te Chen ◽  
Jean Lu ◽  
Shih-Yi Wu ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Cellular Transcription Factor ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr ◽  
Spontaneous Expression ◽  
Early Growth Response 1

ABSTRACT Early growth response 1 (Egr-1) is a cellular transcription factor involved in diverse biologic functions. Egr-1 has been associated with Epstein-Barr virus (EBV) infection, but it is still unknown whether any EBV protein regulates Egr-1 expression. In this study, we first showed that EBV reactivation is involved in upregulation of Egr-1 and that Egr-1 can be induced by Zta, an EBV lytic transactivator. Zta not only binds to the Egr-1 promoter but also activates the ERK signaling pathway to trigger binding of Elk-1 to the Egr-1 promoter. In addition, knockdown of Egr-1 significantly reduces the spontaneous expression of Zta and Rta in EBV-infected 293 cells, suggesting that a positive-feedback network involving Egr-1 is required for EBV reactivation. This study also implies that Zta has the potential to affect expression of certain genes through Egr-1.

scholarly journals Cellular Immediate-Early Gene Expression Occurs Kinetically Upstream of Epstein-Barr Virus bzlf1 and brlf1 following Cross-Linking of the B Cell Antigen Receptor in the Akata Burkitt Lymphoma Cell Line

2010 ◽  
Vol 84 (23) ◽  
pp. 12405-12418 ◽  
Author(s):  
Jianjiang Ye ◽  
Lyndle Gradoville ◽  
George Miller
Keyword(s):  
Signal Transduction ◽  
Protein Synthesis ◽  
Epstein Barr Virus ◽  
Growth Response ◽  
Early Growth ◽  
Lytic Cycle ◽  
Cross Linking ◽  
Early Growth Response ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT The Epstein-Barr virus (EBV) lytic activator genes bzlf1 and brlf1 are conventionally referred to as immediate-early (IE) genes. However, previous studies showed that the earliest expression of these genes was blocked by cycloheximide when the EBV lytic cycle was induced by histone deacetylase (HDAC) inhibitors and protein kinase C agonists. Anti-IgG activates a complex signal transduction pathway that leads to EBV lytic activation in the Akata cell line. Here we demonstrate that in Akata cells, where lytic cycle activation occurs very rapidly after anti-IgG treatment, de novo protein synthesis is also required for induction of bzlf1 and brlf1 expression. New protein synthesis is required up to 1.25 h after application of anti-IgG; bzlf1 and brlf1 mRNAs can be detected 1.5 h after anti-IgG. Five cellular IE genes were shown to be expressed by 1 h after addition of anti-IgG, and their expression preceded that of bzlf1 and brlf1. These include early growth response genes (egr1, egr2, and egr3) and nuclear orphan receptors (nr4a1 and nr4a3). These genes were activated by anti-IgG treatment of Akata cells with and without the EBV genome; therefore, their expression was not dependent on expression of any EBV gene product. EGR1, EGR2, and EGR3 proteins were kinetically upstream of ZEBRA and Rta proteins. Expression of EGR1, ZEBRA, and Rta proteins were inhibited by bisindolylmaleimide X, a selective inhibitor of PKC. The findings suggest a revised model in which the signal transduction cascade activated by cross-linking of the B cell receptor induces expression of cellular IE genes, such as early growth response and nuclear orphan receptor genes, whose products, in turn, regulate bzlf1 and brlf1 expression.

scholarly journals Early Growth Response Gene Upregulation in Epstein–Barr Virus (EBV)-Associated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1484
Author(s):  
Jonathan Kerr
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Psychological Stress ◽  
Epstein Barr Virus ◽  
Growth Response ◽  
Chronic Fatigue ◽  
Early Growth ◽  
Early Growth Response ◽  
Barr Virus ◽  
Fatigue Syndrome ◽  
Epstein Barr

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease exhibiting a variety of symptoms and affecting multiple systems. Psychological stress and virus infection are important. Virus infection may trigger the onset, and psychological stress may reactivate latent viruses, for example, Epstein–Barr virus (EBV). It has recently been reported that EBV induced gene 2 (EBI2) was upregulated in blood in a subset of ME/CFS patients. The purpose of this study was to determine whether the pattern of expression of early growth response (EGR) genes, important in EBV infection and which have also been found to be upregulated in blood of ME/CFS patients, paralleled that of EBI2. EGR gene upregulation was found to be closely associated with that of EBI2 in ME/CFS, providing further evidence in support of ongoing EBV reactivation in a subset of ME/CFS patients. EGR1, EGR2, and EGR3 are part of the cellular immediate early gene response and are important in EBV transcription, reactivation, and B lymphocyte transformation. EGR1 is a regulator of immune function, and is important in vascular homeostasis, psychological stress, connective tissue disease, mitochondrial function, all of which are relevant to ME/CFS. EGR2 and EGR3 are negative regulators of T lymphocytes and are important in systemic autoimmunity.

scholarly journals The early growth response-1 (EGR-1) gene is critical to reperfusion following acute vascular obstruction: Results from a knockout mouse ischemia model

2003 ◽  
Vol 41 (6) ◽  
pp. 279
Author(s):  
Paul Schalch ◽  
Ramaswamy Ramchandran ◽  
David Y. Kim ◽  
Gerald Patejunas ◽  
Mauricio A. Retuerto ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Vascular Obstruction ◽  
Early Growth Response 1

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.

Social isolation stress down-regulates cortical early growth response 1 (Egr-1) expression in mice

2012 ◽  
Vol 73 (3) ◽  
pp. 257-262 ◽  
Author(s):  
Kinzo Matsumoto ◽  
Kazuya Ono ◽  
Hirofumi Ouchi ◽  
Ryohei Tsushima ◽  
Yukihisa Murakami
Keyword(s):  
Social Isolation ◽  
Growth Response ◽  
Early Growth ◽  
Isolation Stress ◽  
Early Growth Response ◽  
Social Isolation Stress ◽  
Early Growth Response 1

scholarly journals Chlorpromazine activates p21Waf1/Cip1gene transcription via early growth response-1 (Egr-1) in C6 glioma cells

2010 ◽  
Vol 42 (5) ◽  
pp. 395 ◽  
Author(s):  
Soon Young Shin ◽  
Chang Gun Kim ◽  
Se Hyun Kim ◽  
Yong Sik Kim ◽  
Yoongho Lim ◽  
...  
Keyword(s):  
Growth Response ◽  
Glioma Cells ◽  
Early Growth ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Early Growth Response ◽  
Early Growth Response 1
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