Effect of n-butyrate on cellular and viral DNA synthesis in cells latently infected with Epstein-Barr virus

Saemundsen, Ari K.; Kallin, Bengt; Klein, George

doi:10.1016/0042-6822(80)90326-8

Cited by 67 publications

(37 citation statements)

References 24 publications

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“…Indeed, sodium butyrate, another short-chain fatty acid, unbranched in contrast to VPA, was shown to induce HCMV replication in human endothelial cells (Radsak et al, 1989) and in a human epithelial cell line (Tanaka et al, 1991). This compound had been previously described to induce a variety of morphological and biochemical changes in different cell types (Prasad & Sinha, 1976), and also to stimulate the replication of other herpesviruses, EpsteinBarr virus and herpes simplex virus (Luka et al, 1979;Saemundsen et al, 1980;Ash, 1986) and more recently HIV (Bohan et al, 1989;Laughlin et al, 1993). We had reported that VPA also stimulated HIV replication (Simon et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Kuntz-Simon

Obert

1995

Journal of General Virology

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Valproic acid (VPA), a simple branched-chain fatty acid having anticonvulsant activity and used in the treatment of many forms of epilepsy, markedly stimulated human cytomegalovirus (HCMV) replication in human fibroblasts (MRC-5 cells). The maximum level of stimulation was reached when cells were treated for 24 h before infection. The enhancement of virus replication correlated with an increase in the number of immediate early (IE) and early (E) antigen-positive cells. VPA also induced expression of IE antigens after transfection of fibroblasts with a plasmid containing the entire IE1-2 region. Moreover, VPA stimulated the HCMV IE1-2 promoter/enhancer-mediated expression of fl-galactosidase in a stably transfected Jurkat T cell line. Recently, VPA was shown to inhibit glutathione reductase in human red blood cells, but an action through the glutathione metabolic pathway can be eliminated in this case, since VPA decreased the intracellular level of glutathione in Jurkat T cells but not in MRC-5 cells. The ability of VPA to stimulate HCMV replication provides an attractive model for studying the molecular mechanism of the regulation of HCMV IE1-2 gene expression.

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Section: Discussionmentioning

confidence: 99%

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Kuntz-Simon

Obert

1995

Journal of General Virology

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“…In latently infected B lymphocytes, EBV gene expression is packaged in chromatin, which is likely to contribute to the repression of lytic gene expression (18,59). Viral reactivation can be stimulated by addition of sodium butyrate, a pleiotropic agent which is a potent inhibitor of histone deacetylases, suggesting that chromatin and histone acetylation may regulate EBV reactivation (35,56). Thus, it seems likely that HATs should promote viral reactivation.…”

Section: Discussionmentioning

confidence: 99%

“…The latent virus exists as a chromatin-associated, multicopy episome with highly restricted transcription patterns (18,59). Reactivation of latent EBV can be induced by several different chemicals, including phorbol esters (72), calcium ionophores (20), 5-azacytidine (5), and sodium butyrate (56). These reagents relieve multiple levels of transcriptional repression and promote transcriptional activation of the immediateearly genes of EBV.…”

Section: Epstein-barr Virus (Ebv) Establishes a Latent Infection Inmentioning

confidence: 99%

The Amino-Terminal C/H1 Domain of CREB Binding Protein Mediates Zta Transcriptional Activation of Latent Epstein-Barr Virus

Zerby

Chen

Poon

et al. 1999

Molecular and Cellular Biology

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Latent Epstein-Barr virus (EBV) is maintained as a nucleosome-covered episome that can be transcriptionally activated by overexpression of the viral immediate-early protein, Zta. We show here that reactivation of latent EBV by Zta can be significantly enhanced by coexpression of the cellular coactivators CREB binding protein (CBP) and p300. A stable complex containing both Zta and CBP could be isolated from lytically stimulated, but not latently infected RAJI nuclear extracts. Zta-mediated viral reactivation and transcriptional activation were both significantly inhibited by coexpression of the E1A 12S protein but not by an N-terminal deletion mutation of E1A (E1A⌬2-36), which fails to bind CBP. Zta bound directly to two related cysteine-and histidine-rich domains of CBP, referred to as C/H1 and C/H3. These domains both interacted specifically with the transcriptional activation domain of Zta in an electrophoretic mobility shift assay. Interestingly, we found that the C/H3 domain was a potent dominant negative inhibitor of Zta transcriptional activation function. In contrast, an amino-terminal fragment containing the C/H1 domain was sufficient for coactivation of Zta transcription and viral reactivation function. Thus, CBP can stimulate the transcription of latent EBV in a histone acetyltransferase-independent manner mediated by the CBP amino-terminal C/H1-containing domain. We propose that CBP may regulate aspects of EBV latency and reactivation by integrating cellular signals mediated by competitive interactions between C/H1, C/H3, and the Zta activation domain.

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“…D98/HR1 cells were transfected with a Zta-expressing plasmid (ZtaSR␣ or Zta-pCDNA3 [66]) using the DOSPER transfection reagent (Boehringer Mannheim, Indianapolis, Ind. ); Raji and CB23 cells were grown for 1 to 3 days in medium containing 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 ng/ml) and sodium butyrate (3 mM) (47,70); and Akata cells were exposed to goat antibodies against human immunoglobulin G (IgG; Boehringer) which had been dialyzed against phosphate-buffered saline (PBS) to remove sodium azide and added to the medium at 10 ng/ml for 1 to 2 days (59). Rta was expressed in HEp-2 cells by transfection with plasmid pRta-RTS2 (48).…”

Section: Methodsmentioning

confidence: 99%

Lytic but Not Latent Replication of Epstein-Barr Virus Is Associated with PML and Induces Sequential Release of Nuclear Domain 10 Proteins

Bell

Lieberman

Maul

2000

J Virol

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Nuclear domains called ND10 (nuclear domain 10) are discrete nuclear protein aggregations characterized by a set of interferon-upregulated proteins including Sp100 and PML, where papova-, adeno-, and herpesviruses begin their transcription and DNA replication. Both the alpha-and betaherpesvirus subfamilies disrupt ND10 upon infection by dispersing and/or destroying ND10-associated proteins. We studied the effect of the gammaherpesvirus Epstein-Barr virus (EBV) on ND10 and its spatial distribution in the nucleus of cells during latency and lytic reactivation. In latently infected Burkitt's lymphoma, lymphoblastoid, and D98/HR1 cells, ND10 were intact, as judged by immunofluorescence localization of PML, Sp100, NDP55, and Daxx. Fluorescent in situ hybridization revealed no association between viral episomes and ND10 during latency, implying that the maintenance replication of EBV, which depends on host cell proliferation, occurs independent of ND10. As in mitosis, the EBV genomes were attached to interphase chromosomes, suggesting that they are unable to move freely within the interchromosomal space and thus unable to associate with the interchromosomally located ND10 or other nuclear domains. Upon lytic activation, ND10 became dispersed in cells expressing lytic proteins. Redistribution of ND10 proteins occurred sequentially at different stages of the lytic cycle, with Sp100, Daxx, and NDP55 dispersed before and PML dispersed after the onset of lytic replication. ND10 remnants were retained until the early stages of lytic replication, and replicating EBV genomes were frequently found beside this nuclear domain; the number of replication domains was usually lower than the average latent virus frequency. Thus, latency does not require or induce interaction of EBV with ND10 for transcription and replication, whereas lytic replication triggers dispersion of ND10 proteins and occurs in close association with PML aggregates. The required movement of chromosome-attached latent EBV episomes to ND10 after reactivation from latency might include physical release of the chromosome-bound episomes. Only episomes contacting ND10 after such a release might be able to begin lytic replication.The eukaryotic nucleus is a highly compartmentalized structure that can be roughly divided into chromosomal domains and interchromosomal space. The latter compartment harbors a variety of discrete structures known as nuclear domains or nuclear bodies, which are composed of defined sets of proteins, sometimes associated with RNAs (reviewed in reference 28). One of these structures, termed PML (promyelocytic leukemia protein) oncogenic domain, PML body, or nuclear domain 10 (ND10), was originally characterized by the presence of the autoantigen of patients with primary biliary cirrhosis, Sp100 (58). Other proteins found in ND10 include NDP55 (4) and PML, which was identified in an oncogenic translocation with the retinoic acid receptor in promyelocytic leukemia and may have functions in major histocompatibility complex gene expression and apop...

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Effect of n-butyrate on cellular and viral DNA synthesis in cells latently infected with Epstein-Barr virus

Cited by 67 publications

References 24 publications

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

The Amino-Terminal C/H1 Domain of CREB Binding Protein Mediates Zta Transcriptional Activation of Latent Epstein-Barr Virus

Lytic but Not Latent Replication of Epstein-Barr Virus Is Associated with PML and Induces Sequential Release of Nuclear Domain 10 Proteins

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