Epstein-Barr virus latent membrane protein transactivates the human immunodeficiency virus type 1 long terminal repeat through induction of NF-kappa B activity

Hammarskjöld, Marie Louise; Simurda, M C

doi:10.1128/jvi.66.11.6496-6501.1992

Cited by 195 publications

(63 citation statements)

References 50 publications

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“…This in no way undermines our conclusions, rather it adds to the body of evidence that EBV infection is but one route to the development of this tumor. For example, a major signaling function of LMP1 is to constitutively activate NF-kB [71][72][73] and many EBV-negative cases of HL carry mutations of NF-kB pathway genes that effect the same result [74,75].…”

Section: Discussionmentioning

confidence: 99%

Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation

et al. 2013

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Epstein-Barr virus (EBV) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma. Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4. One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation lifespans. To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture. As anticipated there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation. Of interest to us was a subset of 255 genes that were differentially expressed between EBV and CD40L/IL-4 blasts. Genes which were more highly expressed in EBV blasts were substantially and significantly enriched for a set of interferon-stimulated genes which on further in silico analyses were found to be repressed by IL-4 in other cell contexts and to be up-regulated in micro-dissected malignant cells from Hodgkin's lymphoma biopsies when compared to their normal germinal center cell counterparts. We hypothesized that EBV and IL-4 were targeting and discordantly regulating a common set of genes. This was supported experimentally in our B cell model where IL-4 stimulation partially reversed transcriptional changes which follow EBV infection and it impaired the efficiency of EBV-induced B cell transformation. Taken together, these data suggest that the discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy.

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Section: Discussionmentioning

confidence: 99%

Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation

et al. 2013

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“…Therefore, it was not surprising to learn that LMP1 also downregulates pro-apoptotic factors like Bax (Bcl-2associated protein x), an antagonist of Bcl-2 function [27]. A breakthrough in the field has been the observation that LMP1 activates the transcription factor NF-jB [21,28,29]. Meanwhile, NF-jB is regarded as a major factor by which LMP1 regulates gene expression and exerts its cellular effects [24,30].…”

Section: Lmp1 Controls Apoptosis and Proliferationmentioning

confidence: 99%

Signal transduction by the Epstein‐Barr virus oncogene latent membrane protein 1 (LMP1)

Kieser¹

2007

Signal Transduction

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The latent membrane protein 1 (LMP1) of Epstein-Barr virus is a viral oncogene with the potential to antagonize apoptosis and senescence as well as to promote cellular survival and proliferation. LMP1 acts like a constitutively active receptor recruiting signalling molecules typically employed by the cellular tumour necrosis factor-receptor (TNF-R) and Toll-like/interleukin-1-receptor (TIR) families. LMP1 activates the classical and alternative NF-jB pathways, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), the JAK/STAT and phosphatidylinositol 3-kinase (PI3K) pathways. In this article, interactions of LMP1 with host cell signal transduction pathways and their role in LMP1-induced cell transformation are reviewed.

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“…In Burkitt's lymphoma cell lines LMP1 induces the expression of B cell activation markers CD23 and CD40 and cell adhesion molecules ICAM1, LFA1 and LFA3 and stimulates NF-iB activity (Wang,F. et al, 1990;Hammarskjoeld and Simurda, 1992;Laherty et al, 1992;Huen et al, 1995;Mitchell and Sugden, 1995). In primary human B cells LMP1 similarly stimulates some of the early events of B cell immortalization, like cellular enlargement, up-regulation of B cell markers and adhesion molecules and transient induction of DNA synthesis (Peng and Lundgren, 1992).…”

Section: Addition Ebna2mentioning

confidence: 99%

Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.

Zimber-Strobl¹,

Kempkes²,

Marschall³

et al. 1996

The EMBO Journal

103

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Epstein‐Barr virus (EBV) infects human primary B lymphocytes and induces and maintains proliferation of these cells efficiently in vitro. Mutants of Epstein‐Barr virus which express EBV nuclear antigen 2 (EBNA2) in a conditional fashion allow dissection of individual contributions of viral genes to B cell immortalization. EBNA2 is a transcriptional activator of cellular and viral genes, including the viral latent membrane protein 1 (LMP1), which is essential for B cell immortalization and has oncogenic effects in non‐lymphoid cells. To analyze the role of this gene in B cell immortalization, LMP1 was constitutively expressed in B cells infected with EBV carrying a conditional EBNA2 allele. In the absence of functional EBNA2, LMP1 was incapable of sustaining B cell proliferation in two independent assays but induced a phenotype consistent with prolonged cell viability. Activation of CD40 displayed a comparable phenotype. These data indicate that both CD40 activation and LMP1 expression may use a common pathway for B cell activation. Proliferation of human B cells, however, requires one or more additional signals triggered by EBNA2.

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Epstein-Barr virus latent membrane protein transactivates the human immunodeficiency virus type 1 long terminal repeat through induction of NF-kappa B activity

Cited by 195 publications

References 50 publications

Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation

Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation

Signal transduction by the Epstein‐Barr virus oncogene latent membrane protein 1 (LMP1)

Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.

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