Molecular Basis of Cytotoxicity of Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) in EBV Latency III B Cells: LMP1 Induces Type II Ligand-Independent Autoactivation of CD95/Fas with Caspase 8-Mediated Apoptosis

Clorennec, Christophe Le; Ouk, Tan‐Sothéa; Youlyouz-Marfak, Ibtissam; Panteix, Stéphanie; Martin, Catherine-Claude; Rastelli, Julia; Adriaenssens, Éric; Zimber-Strobl, Ursula; Cottet, J; Feuillard, Jean; Jayat-Vignoles, Chantal

doi:10.1128/jvi.02250-07

Cited by 51 publications

(37 citation statements)

References 62 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with the results of the present study, Kijima et al (14) knocked-down the LMP1 gene in NPC cells and identified that the cleavage of caspase-3 and -8 and poly(ADP-ribose) polymerase 1 was increased. However, in another study, LMP1 activated caspase-8, -9, -3 and -7 via the induction of Fas overexpression in lymphoblastoid cell lines (32). The inconsistencies observed between these studies may be attributed to the dual effects of LMP1 to induce apoptosis, which was also observed in the study conducted by Chen and Chen (33).…”

Section: Discussionmentioning

confidence: 37%

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

Yang¹,

Li²,

Yang³

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in the majority of tumor cells, whilst sparing normal cells. However, the potential use of TRAIL in the treatment of cancer is limited by the inevitable emergence of drug resistance. The present study reports the upregulation of latent membrane protein 1 (LMP1)-induced TRAIL resistance via the enhanced expression of X-linked inhibitor of apoptosis protein (XIAP) in nasopharyngeal carcinoma (NPC) cells. LMP1-positive NPC cells were indicated to be more sensitive to TRAIL compared with LMP1-negative NPC cells in three NPC cell lines. CNE-1 is a LMP1-negative NPC cell line that was transfected with pGL6-LMP1; following which, sensitivity to TRAIL decreased. LMP1-induced TRAIL resistance was associated with the decreased cleavage of caspase-8,-3 and -9, BH3 interacting domain death agonist (Bid) and mitochondrial depolarization, without any effects on the expression of the death receptors, B-cell lymphoma (Bcl)-2 and Bcl-extra long. Knockdown of XIAP with small interfering RNA increased caspase-3 and -9 and Bid cleavage, and prevented LMP1-induced TRAIL resistance. Furthermore, embelin, the inhibitor of XIAP, prevented LMP1-induced TRAIL resistance in the Epstein-Barr virus (EBV)-positive CNE-1-LMP1 and C666-1 NPC cell lines. However, embelin did not enhance TRAIL-induced apoptosis in NP-69, which was used as a benign nasopharyngeal epithelial cell line. These data show that LMP1 inhibits TRAIL-mediated apoptosis by upregulation of XIAP. Embelin may be used in an efficacious and safe manner to prevent LMP1-induced TRAIL resistance. The present study may have implications for the development and validation of novel strategies to prevent TRAIL resistance in EBV-positive NPC.

show abstract

Section: Discussionmentioning

confidence: 37%

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

Yang¹,

Li²,

Yang³

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…In relation to this point, the FR sequence is also known to be critical for the upregulation of EBV latent membrane protein-1 (LMP-1) promoter (6). The truncated FR (FR20) may result in the overstimulation of the LMP-1 promoter and the overproduction of the LMP-1 protein, which may be disadvantageous for B-cell transformation due to its cytostatic or cytotoxic effects (4,8,20). Presumably, the preservation of the full-length FR (FR29) is important for the appropriate expression levels of viral transforming genes in addition to its contribution to the episomal persistence of the complete EBV genome.…”

Section: Discussionmentioning

confidence: 99%

Distinctive Effects of the Epstein-Barr Virus Family of Repeats on Viral Latent Gene Promoter Activity and B-Lymphocyte Transformation

Ali

Saito

Shibata

et al. 2009

J Virol

View full text Add to dashboard Cite

The Epstein-Barr virus (EBV), a human B-lymphotropic gamma herpesvirus, contains multiple repetitive sequences within its genome. A group of repetitive sequences, known as the family of repeats (FR), contains multiple binding sites for the viral trans-acting protein EBNA-1. The FR sequences are important for viral genome maintenance and for the regulation of the promoter involved in viral latent gene expression. It has been reported that a palindromic sequence with a putative secondary structure exists at the 3 end of the FR in the genome of the EBV B95-8 strain and that this palindromic sequence has been deleted from the FR of the commonly used EBV miniplasmids. For the first time, we cloned an EBV B95-8 DNA fragment containing the full-length FR, which enabled us to examine the functional difference between full-length and deleted FRs. The full-length FR, like the deleted FR, functioned as a transcriptional enhancer of the viral latent gene promoter, but that transactivation was significantly attenuated in the case of the full-length FR. No significant enhancement of replication was observed when the deleted FR was replaced with the full-length FR in an EBV miniplasmid. By contrast, when the same set of FR sequences were tested in the context of the complete EBV genome, the full-length FR resulted in more-efficient B-cell transformation than the deleted FR. We propose that the presence of the full-length FR contributes to the precise regulation of the viral latent promoter and increases the efficiency of B-cell transformation.

show abstract

“…Cells with the highest level of LMP1 have enhanced MHC class I expression and are preferentially killed by T cells in vitro (14). In addition, LMP1 activates CD95 expression, promoting FAS-mediated killing by T cells (17). Moreover, LMP1 induced early-onset B cell lymphomas in a recent LMP1 transgenic mouse model only when T cell function was inhibited, since LMP1 + B…”

Section: Introductionmentioning

confidence: 99%

LMP1-deficient Epstein-Barr virus mutant requires T cells for lymphomagenesis

Dong¹,

Xu²,

Plowshay³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

formation comparison, the P value was calculated using a 2-tailed Fisher exact test. For viral load comparison, the P value was calculated using the Wilcoxon rank-sum test. A P value less than 0.05 was considered significant.Study approval. All animal experiments were approved by the University of Wisconsin-Madison IACUC and conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals. For human AIDS-related lymphomas, cases were collected from the Department of Pathology and Laboratory Medicine of Weill Cornell Medical College. All human samples, obtained with IRB and biospecimen use approval, were residual cases after diagnosis.

show abstract

Molecular Basis of Cytotoxicity of Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) in EBV Latency III B Cells: LMP1 Induces Type II Ligand-Independent Autoactivation of CD95/Fas with Caspase 8-Mediated Apoptosis

Cited by 51 publications

References 62 publications

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

Distinctive Effects of the Epstein-Barr Virus Family of Repeats on Viral Latent Gene Promoter Activity and B-Lymphocyte Transformation

LMP1-deficient Epstein-Barr virus mutant requires T cells for lymphomagenesis

Contact Info

Product

Resources

About