scholarly journals Differential Hyperacetylation of Histones H3 and H4 upon Promoter-Specific Recruitment of EBNA2 in Epstein-Barr Virus Chromatin

2003 ◽  
Vol 77 (14) ◽  
pp. 8166-8172 ◽  
Author(s):  
Nathalie Alazard ◽  
Henri Gruffat ◽  
Edwige Hiriart ◽  
Alain Sergeant ◽  
Evelyne Manet
Keyword(s):  
B Lymphocytes ◽  
Chromatin Immunoprecipitation ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Viral Promoters ◽  
Epstein Barr ◽  
Cellular Dna ◽  
First Time

ABSTRACT Epstein-Barr virus nuclear antigen 2 (EBNA2) is a transcriptional activator involved in the immortalization of B lymphocytes by the virus. EBNA2 is targeted to the promoters of its responsive genes, via interaction with cellular DNA-binding proteins. Using chromatin immunoprecipitation assays, we show for the first time the conditional recruitment of EBNA2 on two specific viral promoters in vivo and demonstrate a correlation between this recruitment and a local change in the acetylation of histones H3 and H4, which is promoter dependent.

scholarly journals Activated Mouse Notch1 Transactivates Epstein-Barr Virus Nuclear Antigen 2-Regulated Viral Promoters

1999 ◽  
Vol 73 (4) ◽  
pp. 2770-2780 ◽  
Author(s):  
Heike Höfelmayr ◽  
Lothar J. Strobl ◽  
Charlotte Stein ◽  
Gerhard Laux ◽  
Gabriele Marschall ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Notch Signalling ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Cellular Factors ◽  
Cell Immortalization ◽  
Viral Genes ◽  
Viral Promoters ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for B-cell immortalization by EBV, most probably by its ability to transactivate a number of cellular and viral genes. EBNA2-responsive elements (EBNA2REs) have been identified in several EBNA2-regulated viral promoters, each of them carrying at least one RBP-Jκ recognition site. RBP-Jκ recruits EBNA2 to the EBNA2RE and, once complexed to EBNA2, is converted from a repressor into an activator. An activated form of the cellular receptor Notch also interacts with RBP-Jκ, providing a link between EBNA2 and Notch signalling. To determine whether activated Notch is able to transactivate EBNA2-responsive viral promoters, we performed cotransfection experiments with activated mouse Notch1 (mNotch1-IC) and luciferase constructs of the BamHI C, LMP1, and LMP2A promoters. We present here evidence that mNotch1-IC transactivates viral promoters known to be regulated by EBNA2. As shown for EBNA2, mutations or deletions of the RBP-Jκ sites diminish or eliminate mNotch1-IC-mediated transactivation of the promoters, pointing to an essential role for Notch–RBP-Jκ interaction. In addition to RBP-Jκ, other cellular factors may bind within the EBNA2REs of viral promoters. While some factors appear to play an important role in both EBNA2- and mNotch1-IC-mediated transactivation, others are only important for the activity of either EBNA2 or mNotch1-IC. We could observe specific mNotch1-IC-responsive regions, thereby throwing more light upon which cofactors interact with EBNA2 and mNotch1-IC, thus enabling them to become functionally transactivators in vivo.

Repeat arrays in cellular DNA related to the Epstein-Barr virus IR3 repeat

1985 ◽  
Vol 5 (3) ◽  
pp. 457-465
Author(s):  
M Heller ◽  
E Flemington ◽  
E Kieff ◽  
P Deininger
Keyword(s):  
Epstein Barr Virus ◽  
Tandem Repeats ◽  
Protein Domain ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr ◽  
Cellular Dna ◽  
The Relationship ◽  
Simple Sequence ◽  
Tandem Arrays

We isolated clones and determined the sequence of portions of mouse and human cellular DNA which cross-hybridize strongly with the IR3 repetitive region of Epstein-Barr virus. The sequences were found to be tandem arrays of a simple sequence based on the triplet GGA, very similar to the IR3 repeat. The cellular repeats have distinct differences from the viral repeat region, however, and their sequences do not appear capable of being translated into a purely glycine-plus-alanine protein domain like the portion of the Epstein-Barr nuclear antigen coded by IR3. Although the relationship between IR3 and the cellular repeats is left unclear, the cellular repeats have many interesting features. The tandem arrays are about 1 to several kilobases long, much shorter than satellite tandem repeats and larger than other interspersed, tandem repeats. Each of the repeats is a distinct variation, perhaps diverged from a common sequence, (GGA)n. This family is present in the genomes of all species tested and appears to be a ubiquitous feature of all higher eucaryotic genomes.

scholarly journals Development of suppressor T lymphocytes for Epstein-Barr virus-induced B-lymphocyte outgrowth during acute infectious mononucleosis: assessment by two quantitative systems

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 510-517 ◽  
Author(s):  
RT Schooley ◽  
BF Haynes ◽  
J Grouse ◽  
C Payling-Wright ◽  
AS Fauci ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Acute Stage ◽  
Cell Mediated Immunity ◽  
Barr Virus ◽  
Epstein Barr

Abstract A system of 3H-thymidine incorporation by lymphocytes in culture for 3 wk has been utilized for quantitative assessment of the ability of T lymphocytes to inhibit outgrowth of autologous Epstein-Barr virus (EBV) transformed B lymphocytes. Lymphocytes from EBV-seronegative individuals lack the ability to suppress outgrowth of autologous EBV- transformed B lymphocytes. This capability appears during the course of primary EBV-induced infectious mononucleases (IM) as the atypical lymphocytosis is subsiding and persists for years after recovery from primary EBV infection. The ability of T lymphocytes from EBV- seropositive subjects or convalescent IM patients to inhibit B- lymphocyte outgrowth is not HLA restricted. Thus, T lymphocytes capable of inhibition of in vitro EBV-induced B-cell outgrowth emerge during the acute stage of IM and may represent an important control mechanism of EBV-induced B-lymphocyte proliferation in vivo. The system provides a highly sensitive quantitative means for in vitro assessment of cell- mediated immunity to EBV.

scholarly journals The ATM/ATR Signaling Effector Chk2 Is Targeted by Epstein-Barr Virus Nuclear Antigen 3C To Release the G2/M Cell Cycle Block

2007 ◽  
Vol 81 (12) ◽  
pp. 6718-6730 ◽  
Author(s):  
Tathagata Choudhuri ◽  
Subhash C. Verma ◽  
Ke Lan ◽  
Masanao Murakami ◽  
Erle S. Robertson
Keyword(s):  
Cell Cycle ◽  
B Lymphocytes ◽  
Epstein Barr Virus ◽  
Cell Cycle Checkpoint ◽  
Nuclear Antigen ◽  
M Cell ◽  
Barr Virus ◽  
Cycle Checkpoint ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) infects most of the human population and persists in B lymphocytes for the lifetime of the host. The establishment of latent infection by EBV requires the expression of a unique repertoire of genes. The product of one of these viral genes, the EBV nuclear antigen 3C (EBNA3C), is essential for the growth transformation of primary B lymphocytes in vitro and can regulate the transcription of a number of viral and cellular genes important for the immortalization process. This study demonstrates an associated function of EBNA3C which involves the disruption of the G2/M cell cycle checkpoint. We show that EBNA3C-expressing lymphoblastoid cell lines treated with the drug nocodazole, which is known to block cells at the G2/M transition, did not show a G2/M-specific checkpoint arrest. Analyses of the cell cycles of cells expressing EBNA3C demonstrated that the expression of this essential EBV nuclear antigen is capable of releasing the G2/M checkpoint arrest induced by nocodazole. This G2/M arrest in response to nocodazole was also abolished by caffeine, suggesting an involvement of the ATM/ATR signaling pathway in the regulation of this cell cycle checkpoint. Importantly, we show that the direct interaction of EBNA3C with Chk2, the ATM/ATR signaling effector, is responsible for the release of this nocodazole-induced G2/M arrest and that this interaction leads to the serine 216 phosphorylation of Cdc25c, which is sequestered in the cytoplasm by 14-3-3. Overall, our data suggest that EBNA3C can directly regulate the G2/M component of the host cell cycle machinery, allowing for the release of the checkpoint block.

scholarly journals Epstein-Barr Virus (EBV) Nuclear Antigen 1 Colocalizes with Cellular Replication Foci in the Absence of EBV Plasmids

2003 ◽  
Vol 77 (6) ◽  
pp. 3824-3831 ◽  
Author(s):  
Sayuri Ito ◽  
Kazuo Yanagi
Keyword(s):  
Epstein Barr Virus ◽  
Short Pulse ◽  
Protein A ◽  
Nuclear Antigen ◽  
Metaphase Chromosomes ◽  
Barr Virus ◽  
Replication Foci ◽  
Epstein Barr ◽  
Cellular Replication ◽  
Cellular Dna

ABSTRACT Epstein-Barr virus (EBV) EBNA-1 is the only EBV-encoded protein that is essential for the once-per-cell-cycle replication and maintenance of EBV plasmids in latently infected cells. EBNA-1 binds to the oriP region of latent EBV plasmids and cellular metaphase chromosomes. In the absence of oriP-containing plasmids, EBNA-1 was highly colocalized with cellular DNA replication foci that were identified by immunostaining S-phase cells for proliferating cell nuclear antigen and replication protein A (RP-A) in combination with DNA short pulse-labeling. For the association of EBNA-1 with the cellular replication focus areas, the EBNA-1 regions of amino acids (aa) 8 to 94 and/or aa 315 to 410, but not the RP-A-interacting carboxy-terminal region, were necessary. These results suggest a new aspect of latent virus-cell interactions.

scholarly journals Latent Gene Sequencing Reveals Familial Relationships among Chinese Epstein-Barr Virus Strains and Evidence for Positive Selection of A11 Epitope Changes

2003 ◽  
Vol 77 (21) ◽  
pp. 11517-11530 ◽  
Author(s):  
R. S. Midgley ◽  
A. I. Bell ◽  
D. J. McGeoch ◽  
A. B. Rickinson
Keyword(s):  
Epstein Barr Virus ◽  
Sequence Divergence ◽  
Nuclear Antigen ◽  
Coding Region ◽  
Immune Selection ◽  
Genomic Context ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) strains from the highly HLA-A11-positive Chinese population are predominantly type 1 and show a variety of sequence changes (relative to the contemporary Caucasian prototype strain B95.8) in the nuclear antigen EBNA3B sequences encoding two immunodominant HLA-A11 epitopes, here called IVT and AVF. This has been interpreted by some as evidence of immune selection and by others as random genetic drift. To study epitope variation in a broader genomic context, we sequenced the whole of EBNA3B and parts of the EBNA2, 3A, and 3C genes from each of 31 Chinese EBV isolates. At each locus, type 1 viruses showed <2% nucleotide divergence from the B95.8 prototype while type 2 sequences remained even closer to the contemporary African prototype Ag876. However, type 1 isolates could clearly be divided into families based on linked patterns of sequence divergence from B95.8 across all four EBNA loci. Different patterns of IVT and AVF variation were associated with the different type 1 families, and there was additional epitope diversity within families. When the EBNA3 gene sequences of type 1 Chinese strains were subject to computer-based analysis, particular codons within the A11-epitope-coding region were among the few identified as being under positive or diversifying selection pressure. From these results, and the observation that mutant epitopes are consistently nonimmunogenic in vivo, we conclude that the immune selection hypothesis remains viable and worthy of further investigation.

scholarly journals Repeat arrays in cellular DNA related to the Epstein-Barr virus IR3 repeat.

1985 ◽  
Vol 5 (3) ◽  
pp. 457-465 ◽  
Author(s):  
M Heller ◽  
E Flemington ◽  
E Kieff ◽  
P Deininger
Keyword(s):  
Epstein Barr Virus ◽  
Tandem Repeats ◽  
Protein Domain ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr ◽  
Cellular Dna ◽  
The Relationship ◽  
Simple Sequence ◽  
Tandem Arrays

We isolated clones and determined the sequence of portions of mouse and human cellular DNA which cross-hybridize strongly with the IR3 repetitive region of Epstein-Barr virus. The sequences were found to be tandem arrays of a simple sequence based on the triplet GGA, very similar to the IR3 repeat. The cellular repeats have distinct differences from the viral repeat region, however, and their sequences do not appear capable of being translated into a purely glycine-plus-alanine protein domain like the portion of the Epstein-Barr nuclear antigen coded by IR3. Although the relationship between IR3 and the cellular repeats is left unclear, the cellular repeats have many interesting features. The tandem arrays are about 1 to several kilobases long, much shorter than satellite tandem repeats and larger than other interspersed, tandem repeats. Each of the repeats is a distinct variation, perhaps diverged from a common sequence, (GGA)n. This family is present in the genomes of all species tested and appears to be a ubiquitous feature of all higher eucaryotic genomes.

scholarly journals The Epstein-Barr virus nuclear protein 2 acidic domain forms a complex with a novel cellular coactivator that can interact with TFIIE.

1995 ◽  
Vol 15 (9) ◽  
pp. 4735-4744 ◽  
Author(s):  
X Tong ◽  
R Drapkin ◽  
R Yalamanchili ◽  
G Mosialos ◽  
E Kieff
Keyword(s):  
Epstein Barr Virus ◽  
Nuclear Protein ◽  
Lymphocyte Transformation ◽  
Nuclear Antigen ◽  
Cdna Clones ◽  
Barr Virus ◽  
Acidic Domain ◽  
Epstein Barr

Epstein-Barr virus nuclear antigen 2 (EBNA 2) activates transcription of specific genes and is essential for B-lymphocyte transformation. EBNA 2 has an acidic activation domain which interacts with general transcription factors TFIIB, TFIIH, and TAF40. We now show that EBNA 2 is specifically bound to a novel nuclear protein, p100, and that p100 can coactivate gene expression mediated by the EBNA 2 acidic domain. The EBNA 2 acidic domain was used to affinity purify p100. cDNA clones encoding the p100 open reading frame were identified on the basis of peptide sequences of the purified protein. Antibody against p100 coimmunoprecipitated p100 and EBNA 2 from Epstein-Barr virus-transformed lymphocyte extracts, indicating that EBNA 2 and p100 are complexed in vivo. p100 overexpression in cells specifically augmented EBNA 2 acidic domain-mediated activation. The coactivating effect is probably mediated by p100 interaction with TFIIE. Bacterially expressed p100 specifically adsorbs TFIIE from nuclear extracts, and in vitro-translated p56 or p34 TFIIE subunit can independently bind to p100. p100 also appears to be essential for normal cell growth, since cell viability was reduced by antisense p100 RNA and restored by sense p100 RNA expression.

scholarly journals Physical and Functional Interactions between the Corepressor CtBP and the Epstein-Barr Virus Nuclear Antigen EBNA3C

2001 ◽  
Vol 75 (16) ◽  
pp. 7749-7755 ◽  
Author(s):  
Robert Touitou ◽  
Mark Hickabottom ◽  
Gillian Parker ◽  
Tim Crook ◽  
Martin J. Allday
Keyword(s):  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Rat Embryo ◽  
Barr Virus ◽  
Functional Interactions ◽  
C Terminus ◽  
Epstein Barr ◽  
Repressor Activity

ABSTRACT CtBP has been shown to be a highly conserved corepressor of transcription. E1A and all the various transcription factors to which CtBP binds contain a conserved PLDLS CtBP-interacting domain, and EBNA3C includes a PLDLS motif (amino acids [aa] 728 to 732). Here we show that EBNA3C binds to CtBP both in vitro and in vivo and that the interaction requires an intact PLDLS. The C terminus of EBNA3C (aa 580 to 992) has modest trans-repressor activity when it is fused to the DNA-binding domain of Gal4, and deletion or mutation of the PLDLS sequence ablates this and unmasks a transactivation function within the fragment. However, loss of the CtBP interaction motif had little effect on the ability of full-length EBNA3C to repress transcription. A striking correlation between CtBP binding and the capacity of EBNA3C to cooperate with (Ha-)Ras in the immortalization and transformation of primary rat embryo fibroblasts was also revealed.

Sign in / Sign up

Export Citation Format

Share Document