scholarly journals Truncated Form of the Epstein-Barr Virus Protein EBNA-LP Protects against Caspase-Dependent Apoptosis by Inhibiting Protein Phosphatase 2A

2007 ◽  
Vol 81 (14) ◽  
pp. 7598-7607 ◽  
Author(s):  
Julie Garibal ◽  
Émilie Hollville ◽  
Andrew I. Bell ◽  
Gemma L. Kelly ◽  
Benjamin Renouf ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Protein Phosphatase ◽  
Epstein Barr Virus ◽  
Protein Phosphatase 2A ◽  
Low Molecular Weight ◽  
Truncated Form ◽  
Barr Virus ◽  
Phosphatase 2A ◽  
Epstein Barr ◽  
In Cells

ABSTRACT The Epstein-Barr virus (EBV)-encoded leader protein, EBNA-LP, strongly activates the EBNA2-mediated transcriptional activation of cellular and viral genes and is therefore important for EBV-induced B-cell transformation. However, a truncated form of EBNA-LP is produced in cells infected with variant EBV strains lacking EBNA2 due to a genetic deletion. The function of this truncated form is unknown. We show here that some Burkitt's lymphoma cells harboring defective EBV strains are specifically resistant to the caspase-dependent apoptosis induced by verotoxin 1 (VT-1) or staurosporine. These cells produced low-molecular-weight Y1Y2-truncated isoforms of EBNA-LP, which were partly localized in the cytoplasm. The transfection of sensitive cells with constructs encoding truncated EBNA-LP isoforms, but not full-length EBNA-LP, induced resistance to caspase-mediated apoptosis. Furthermore, VT-1 induced protein phosphatase 2A (PP2A) activation in sensitive cells but not in resistant cells, in which the truncated EBNA-LP interacted with this protein. Thus, the resistance to apoptosis observed in cells harboring defective EBV strains most probably results from the inactivation of PP2A via interactions with low-molecular-weight Y1Y2-truncated EBNA-LP isoforms.

Modulation of Ceramide-Activated Protein Phosphatase 2A Activity by Low Molecular Weight Aromatic Compounds

1998 ◽  
Vol 55 (7) ◽  
pp. 1105-1111 ◽  
Author(s):  
Lorenzo M. Leoni ◽  
Hsien C. Shih ◽  
Lynn Deng ◽  
Chuck Tuey ◽  
Gernot Walter ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Aromatic Compounds ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Low Molecular Weight ◽  
Phosphatase 2A

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 MicroRNA-155 Is an Epstein-Barr Virus-Induced Gene That Modulates Epstein-Barr Virus-Regulated Gene Expression Pathways

2008 ◽  
Vol 82 (11) ◽  
pp. 5295-5306 ◽  
Author(s):  
Qinyan Yin ◽  
Jane McBride ◽  
Claire Fewell ◽  
Michelle Lacey ◽  
Xia Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epstein Barr Virus ◽  
Type I ◽  
Type Iii ◽  
Barr Virus ◽  
Transcriptional Regulatory ◽  
Infected Cells ◽  
Epstein Barr ◽  
Regulated Gene Expression ◽  
In Cells

ABSTRACT The cellular microRNA miR-155 has been shown to be involved in lymphocyte activation and is expressed in Epstein-Barr virus (EBV)-infected cells displaying type III latency gene expression but not type I latency gene expression. We show here that the elevated levels of miR-155 in type III latency cells is due to EBV gene expression and not epigenetic differences in cell lines tested, and we show that expression in EBV-infected cells requires a conserved AP-1 element in the miR-155 promoter. Gene expression analysis was carried out in a type I latency cell line transduced with an miR-155-expressing retrovirus. This analysis identified both miR-155-suppressed and -induced cellular mRNAs and suggested that in addition to direct targeting of 3′ untranslated regions (UTRs), miR-155 alters gene expression in part through the alteration of signal transduction pathways. 3′ UTR reporter analysis of predicted miR-155 target genes identified the transcriptional regulatory genes encoding BACH1, ZIC3, HIVEP2, CEBPB, ZNF652, ARID2, and SMAD5 as miR-155 targets. Western blot analysis of the most highly suppressed of these, BACH1, showed lower expression in cells transduced with a miR-155 retrovirus. Inspection of the promoters from genes regulated in EBV-infected cells and in cells infected with an miR-155 retrovirus identified potential binding sequences for BACH1 and ZIC3. Together, these experiments suggest that the induction of miR-155 by EBV contributes to EBV-mediated signaling in part through the modulation of transcriptional regulatory factors.

scholarly journals The Epstein-Barr Virus (EBV) gN Homolog BLRF1 Encodes a 15-Kilodalton Glycoprotein That Cannot Be Authentically Processed unless It Is Coexpressed with the EBV gM Homolog BBRF3

1998 ◽  
Vol 72 (7) ◽  
pp. 5559-5564 ◽  
Author(s):  
Cathleen M. Lake ◽  
Sara J. Molesworth ◽  
Lindsey M. Hutt-Fletcher
Keyword(s):  
Sialic Acid ◽  
Recombinant Protein ◽  
Epstein Barr Virus ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Mature Form ◽  
Barr Virus ◽  
Epstein Barr ◽  
Antipeptide Antibody ◽  
In Cells

ABSTRACT The Epstein-Barr virus (EBV) homolog of the conserved herpesvirus glycoprotein gN is predicted to be encoded by the BLRF1 open reading frame (ORF). Antipeptide antibody to a sequence corresponding to residues in the predicted BLRF1 ORF immunoprecipitated a doublet of approximately 8 kDa from cells expressing the BLRF1 ORF as a recombinant protein. In addition, four glycosylated proteins of 113, 84, 48, and 15 kDa could be immunoprecipitated from virus-producing cells by the same antibody. The 15-kDa species was the mature form of gN, which carried α2,6-sialic acid residues. The remaining glycoproteins which associated with gN were products of the BBRF3 ORF of EBV, which encodes the EBV gM homolog. The 8-kDa doublet seen in cells expressing recombinant gN comprised precursors of the mature 15-kDa gN. Coexpression of EBV gM with EBV gN was required for authentic processing of the 8-kDa forms to the 15-kDa form.

scholarly journals Inhibition of Epstein-Barr Virus Replication by a Benzimidazole l-Riboside: Novel Antiviral Mechanism of 5,6-Dichloro-2-(Isopropylamino)-1-β-l-Ribofuranosyl-1H-Benzimidazole

1999 ◽  
Vol 73 (9) ◽  
pp. 7271-7277 ◽  
Author(s):  
Valerie L. Zacny ◽  
Eduard Gershburg ◽  
Michelle G. Davis ◽  
Karen K. Biron ◽  
Joseph S. Pagano
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Epstein Barr Virus ◽  
Blot Hybridization ◽  
Lytic Replication ◽  
Viral Dna ◽  
Barr Virus ◽  
Latently Infected ◽  
Ebv Dna ◽  
Epstein Barr

ABSTRACT Although a number of antiviral drugs inhibit replication of Epstein-Barr virus (EBV) in cell culture, and acyclovir (ACV) suppresses replication in vivo, currently available drugs have not proven effective for treatment of EBV-associated diseases other than oral hairy leukoplakia. Benzimidazole riboside compounds represent a new class of antiviral compounds that are potent inhibitors of human cytomegalovirus (HCMV) replication but not of other herpesviruses. Here we characterize the effects of two compounds in this class against lytic replication of EBV induced in a Burkitt lymphoma cell line latently infected with EBV. We analyzed linear forms of EBV genomes, indicative of lytic replication, and episomal forms present in latently infected cells by terminal probe analysis followed by Southern blot hybridization as well as the high-molecular-weight unprocessed viral DNA by pulsed-field gel electrophoresis. d-Ribofuranosyl benzimidazole compounds that act as inhibitors of HCMV DNA maturation, including BDCRB (5,6-dichloro-2-bromo-1-β-d-ribofuranosyl-1H-benzimidazole), did not affect the accumulation of high-molecular-weight or monomeric forms of EBV DNA in the induced cells. In contrast, the generation of linear EBV DNA as well as precursor viral DNA was sensitive to thel-riboside 1263W94 [5,6-dichloro-2-(isopropylamino)-1-β-l-ribofuranosyl-1H-benzimidazole]. The 50% inhibitory concentration range for 1263W94 was 0.15 to 1.1 μM, compared with 10 μM for ACV. Thus, 1263W94 is a potent inhibitor of EBV. In addition, 1263W94 inhibited the phosphorylation and the accumulation of the essential EBV replicative cofactor, early antigen D.

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