scholarly journals Epstein-Barr Virus Immediate-Early Protein BRLF1 Interacts with CBP, Promoting Enhanced BRLF1 Transactivation

2001 ◽  
Vol 75 (13) ◽  
pp. 6228-6234 ◽  
Author(s):  
Jennifer J. Swenson ◽  
Elizabeth Holley-Guthrie ◽  
Shannon C. Kenney
Keyword(s):  
Viral Replication ◽  
Epstein Barr Virus ◽  
Immediate Early ◽  
Transcriptional Activators ◽  
Creb Binding Protein ◽  
Raji Cells ◽  
Barr Virus ◽  
Early Protein ◽  
Epstein Barr ◽  
Multiple Domains

ABSTRACT The Epstein-Barr virus (EBV) immediate-early protein BRLF1 is a transcriptional activator that mediates the switch from latent to lytic viral replication. Many transcriptional activators function, in part, due to an interaction with histone acetylases, such as CREB-binding protein (CBP). Here we demonstrate that BRLF1 interacts with the amino and carboxy termini of CBP and that multiple domains of the BRLF1 protein are necessary for this interaction. Furthermore, we show that the interaction between BRLF1 and CBP is important for BRLF1-induced activation of the early lytic EBV gene SM in Raji cells.

scholarly journals Epstein-Barr Virus Immediate-Early Protein BRLF1 Induces the Lytic Form of Viral Replication through a Mechanism Involving Phosphatidylinositol-3 Kinase Activation

2001 ◽  
Vol 75 (13) ◽  
pp. 6135-6142 ◽  
Author(s):  
Catherine Dayle Darr ◽  
Amy Mauser ◽  
Shannon Kenney
Keyword(s):  
Viral Replication ◽  
Transcriptional Activation ◽  
Epstein Barr Virus ◽  
Adenovirus Vector ◽  
Pi3 Kinase ◽  
Immediate Early ◽  
Kinase Activation ◽  
Barr Virus ◽  
Epstein Barr ◽  
Phosphatidylinositol 3

ABSTRACT Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBV-positive cell lines. BRLF1 is a transcriptional activator that binds directly to a GC-rich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation.

scholarly journals Epstein-Barr Virus Immediate-Early Proteins BZLF1 and BRLF1 Activate the ATF2 Transcription Factor by Increasing the Levels of Phosphorylated p38 and c-Jun N-Terminal Kinases

2000 ◽  
Vol 74 (3) ◽  
pp. 1224-1233 ◽  
Author(s):  
Amy L. Adamson ◽  
Dayle Darr ◽  
Elizabeth Holley-Guthrie ◽  
Robert A. Johnson ◽  
Amy Mauser ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Epstein Barr Virus ◽  
Viral Latency ◽  
Immediate Early ◽  
Expression Vectors ◽  
Protein Z ◽  
Barr Virus ◽  
Ebv Infection ◽  
Early Protein ◽  
Epstein Barr

ABSTRACT Expression of either Epstein-Barr virus (EBV) immediate-early protein BZLF1 (Z) or BRLF1 (R) is sufficient to convert EBV infection from the latent to lytic form. Disruption of viral latency requires transcriptional activation of the Z and R promoters. The Z and R proteins are transcriptional activators, and each immediate-early protein activates expression of the other immediate-early protein. Z activates the R promoter through a direct binding mechanism. However, R does not bind directly to the Z promoter. In this study, we demonstrate that the ZII element (a cyclic AMP response element site) in the Z promoter is required for efficient activation by R. The ZII element has been shown to be important for induction of lytic EBV infection by tetradecanoyl phorbol acetate and surface immunoglobulin cross-linking and is activated by Z through an indirect mechanism. We demonstrate that both R and Z activate the cellular stress mitogen-activated protein (MAP) kinases, p38 and JNK, resulting in phosphorylation (and activation) of the cellular transcription factor ATF2. Furthermore, we show that the ability of R to induce lytic EBV infection in latently infected cells is significantly reduced by inhibition of either the p38 kinase or JNK pathways. In contrast, inhibition of stress MAP kinase pathways does not impair the ability of Z expression vectors to disrupt viral latency, presumably because expression of Z under the control of a strong heterologous promoter bypasses the need to activate Z transcription. Thus, both R and Z can activate the Z promoter indirectly by inducing ATF2 phosphorylation, and this activity appears to be important for R-induced disruption of viral latency.

scholarly journals Epstein-Barr Virus Immediate-Early Protein BZLF1 Is SUMO-1 Modified and Disrupts Promyelocytic Leukemia Bodies

2001 ◽  
Vol 75 (5) ◽  
pp. 2388-2399 ◽  
Author(s):  
Amy L. Adamson ◽  
Shannon Kenney
Keyword(s):  
Cell Lines ◽  
Transcriptional Activation ◽  
Epstein Barr Virus ◽  
Promyelocytic Leukemia ◽  
Lytic Replication ◽  
Immediate Early ◽  
Barr Virus ◽  
Early Protein ◽  
Pml Bodies ◽  
Epstein Barr

ABSTRACT Although the immediate-early proteins of both herpes simplex virus (HSV) and cytomegalovirus (CMV) are known to modify promyelocytic leukemia (PML) (ND10) bodies in the nucleus of the host cell, it has been unclear whether lytic infection with gamma herpesviruses induces a similar effect. The PML protein is induced by interferon, involved in major histocompatibility complex class I presentation, and necessary for certain types of apoptosis. Therefore, it is likely that PML bodies function in an antiviral capacity. SUMO-1 modification of PML is known to be required for the formation of PML bodies. To examine whether Epstein-Barr virus (EBV) lytic replication interferes with PML bodies, we expressed the EBV immediate-early genes BZLF1 (Z) and BRLF1 (R) in EBV-positive cell lines and examined PML localization. Both Z and R expression resulted in PML dispersion in EBV-positive cells. Z but not R expression is sufficient to disrupt PML bodies in EBV-negative cell lines. We show that dispersion of PML bodies by Z requires a portion of the transcriptional activation domain of Z but not the DNA-binding function. As was previously reported for the HSV-1 ICP0 and CMV IE1 proteins, Z reduces the amount of SUMO-1-modified PML. We also found that Z itself is SUMO-1 modified (through amino acid 12) and that Z competes with PML for limiting amounts of SUMO-1. These results suggest that disruption of PML bodies is important for efficient lytic replication of EBV. Furthermore, Z may potentially alter the function of a variety of cellular proteins by inhibiting SUMO-1 modification.

scholarly journals Inhibition of IFN-γ Signaling by an Epstein-Barr Virus Immediate-Early Protein

Immunity ◽  
2001 ◽  
Vol 15 (5) ◽  
pp. 787-799 ◽  
Author(s):  
Thomas E Morrison ◽  
Amy Mauser ◽  
Athena Wong ◽  
Jenny P.-Y Ting ◽  
Shannon C Kenney
Keyword(s):  
Epstein Barr Virus ◽  
Immediate Early ◽  
Barr Virus ◽  
Early Protein ◽  
Ifn Γ ◽  
Epstein Barr

scholarly journals Expression of Epstein–Barr virus BZLF1 immediate-early protein induces p53 degradation independent of MDM2, leading to repression of p53-mediated transcription

Virology ◽  
2009 ◽  
Vol 388 (1) ◽  
pp. 204-211 ◽  
Author(s):  
Yoshitaka Sato ◽  
Noriko Shirata ◽  
Ayumi Kudoh ◽  
Satoko Iwahori ◽  
Sanae Nakayama ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Immediate Early ◽  
Barr Virus ◽  
Early Protein ◽  
Epstein Barr

scholarly journals The C-Mer Gene Is Induced by Epstein-Barr Virus Immediate-Early Protein BRLF1

2004 ◽  
Vol 78 (21) ◽  
pp. 11778-11785 ◽  
Author(s):  
Yuling Li ◽  
Nupam P. Mahajan ◽  
Jennifer Webster-Cyriaque ◽  
Prasanna Bhende ◽  
Gregory K. Hong ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Immediate Early ◽  
Lymphoblastoid Cells ◽  
Barr Virus ◽  
Early Protein ◽  
Hairy Leukoplakia ◽  
Immediate Early Proteins ◽  
Epstein Barr

ABSTRACT BRLF1 (R) is one of two Epstein-Barr virus (EBV) immediate-early proteins that mediate the switch from the latent to the lytic form of viral replication. In this report, we show that R induces expression of the cellular C-mer gene in a variety of cell lines. C-mer expression was detected in lymphoblastoid cells immortalized with wild-type EBV but not in lymphoblastoid cells immortalized with an EBV that had BRLF1 deleted. Oral hairy leukoplakia tongue tissue, which contains the lytic form of EBV replication, also has enhanced C-mer expression. C-mer is a receptor tyrosine kinase activated by the ligand Gas6. C-mer is required for phagocytosis of apoptotic debris by monocytes/macrophages and retinal pigment epithelial cells and is capable of producing an antiapoptotic signal. Modulation of the C-mer signal transduction cascade by a variety of different approaches did not alter the ability of R to induce lytic EBV gene transcription. Therefore, C-mer activation may be important for some other aspect of lytic EBV infection.

scholarly journals Activation of the ERK signal transduction pathway by Epstein–Barr virus immediate-early protein Rta

2008 ◽  
Vol 89 (10) ◽  
pp. 2437-2446 ◽  
Author(s):  
Yu-Hsiu Lee ◽  
Ya-Fang Chiu ◽  
Wen-Hung Wang ◽  
Li-Kwan Chang ◽  
Shih-Tung Liu
Keyword(s):  
Signal Transduction ◽  
Epstein Barr Virus ◽  
Signal Transduction Pathway ◽  
Early Gene ◽  
Immediate Early ◽  
Transduction Pathway ◽  
Binding Studies ◽  
Barr Virus ◽  
Early Protein ◽  
Epstein Barr

BRCA1-associated protein 2 (BRAP2) is known to interact with the kinase suppressor of Ras 1 (KSR1), inhibiting the ERK signal transduction cascade. This study found that an Epstein–Barr virus (EBV) immediate-early protein, Rta, is a binding partner of BRAP2 in yeast and confirmed the binding in vitro by a glutathione S-transferase pull-down assay and in vivo by co-immunoprecipitation in 293(maxi-EBV) cells. Binding studies also showed that Rta and KSR1 interacted with the C-terminal 202 aa region in BRAP2. Additionally, Rta appeared to prevent the binding of KSR1 to BRAP2, activating the ERK signal transduction pathway and the transcription of an EBV immediate-early gene, BZLF1. Activation of the ERK signal transduction pathway by Rta may be critical for the maintenance of the lytic state of EBV.

scholarly journals Epstein-Barr Virus Polymerase Processivity Factor EnhancesBALF2Promoter Transcription as a Coactivator for the BZLF1 Immediate-Early Protein

2009 ◽  
Vol 284 (32) ◽  
pp. 21557-21568 ◽  
Author(s):  
Sanae Nakayama ◽  
Takayuki Murata ◽  
Kazutaka Murayama ◽  
Yoshihiro Yasui ◽  
Yoshitaka Sato ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Immediate Early ◽  
Barr Virus ◽  
Early Protein ◽  
Processivity Factor ◽  
Epstein Barr

scholarly journals The Epstein-Barr Virus BZLF1 Protein Interacts Physically and Functionally with the Histone Acetylase CREB-Binding Protein

1999 ◽  
Vol 73 (8) ◽  
pp. 6551-6558 ◽  
Author(s):  
Amy L. Adamson ◽  
Shannon Kenney
Keyword(s):  
Epstein Barr Virus ◽  
Mutational Analysis ◽  
Binding Protein ◽  
Direct Interaction ◽  
Early Gene ◽  
Creb Binding Protein ◽  
Barr Virus ◽  
Amino Terminal ◽  
Early Protein ◽  
Epstein Barr

ABSTRACT The Epstein-Barr virus (EBV) immediate-early protein BZLF1 (Z) is a key regulator of the EBV latent-to-lytic switch. Z is a transcriptional activator which induces EBV early gene expression. We demonstrate here that Z interacts with CREB-binding protein (CBP), a histone acetylase and transcriptional coactivator. This interaction requires the amino-terminal region of CBP as well as the transactivation and leucine zipper domains of Z. We show that CBP enhances Z-mediated transactivation of EBV early promoters, in reporter gene assays and in the context of the endogenous genome. We also demonstrate that Z decreases CREB transactivation function and that this inhibitory effect is reversed by overexpression of CBP. We show that Z also interacts directly with CREB. However, mutational analysis indicates that Z inhibition of CREB activity requires the direct interaction between Z and CBP but not the direct interaction between Z and CREB. We propose that Z interacts with CBP to enhance viral early gene transcription. In addition, the Z-CBP interaction may control host cellular transcription factor activity through competition for limiting amounts of cellular CBP.

Sign in / Sign up

Export Citation Format

Share Document