Inhibition of in vitro proliferation of Epstein Barr Virus infected B cells by an antisense oligodeoxynucleotide targeted against EBV latent membrane protein LMP1

Mattia, Elena Di; Chichiarelli, Silvia; Hickish, Tamas; Gaeta, Aurelia; Mancini, Carlo; Cunningham, David; Renswoude, Jos van

doi:10.1038/sj.onc.1201183

Cited by 13 publications

(11 citation statements)

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“…The effect of an antisense oligodeoxynucleotide (AS2) targeted against LMP-1 was compared to that of a randomly scrambled version (SC2) used as control (34). Western blotting analysis.…”

Section: Vol 76 2002 Ebv Transformation Of a Monocytic Cell Line 6461mentioning

confidence: 99%

Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation

Masy

Adriaenssens²,

Montpellier

et al. 2002

J Virol

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Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other herpesviruses, EBV is not described as an infectious agent for monocytes. However, recent papers described in vitro infection of monocytes leading to abortive or transient viral expression. In the present study, we report the characterization of E1, a monocytic cell line infected and transformed by EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, major histocompatibility complex class II, and CD80) and the c-fms gene, a highly specific marker for the monocytic lineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell line obtained from one of these tumors (TE1) displayed immunophenotype and functional properties similar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression of the EBNA-1 and LMP-1, but not EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences the phenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and membrane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the first description of a latently infected human monocytic cell line and the first direct demonstration of an instrumental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency.

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“…The effect of an antisense oligodeoxynucleotide (AS2) targeted against LMP-1 was compared to that of a randomly scrambled version (SC2) used as control (34). Western blotting analysis.…”

Section: Vol 76 2002 Ebv Transformation Of a Monocytic Cell Line 6461mentioning

confidence: 99%

Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation

Masy

Adriaenssens²,

Montpellier

et al. 2002

J Virol

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“…This growth transformation requires the cooperative action of at least five "latent" EBV genes. One of these essential latent genes encodes the latent membrane protein 1, which is oncogenic in various experimental models (3,74,77), can enhance cell survival through upregulation of antiapoptotic genes (17,31,52,75), and is essential for continued proliferation of established LCL (47,55). Furthermore, LMP-1 is expressed in the EBV-associated posttransplant lymphoproliferative disorders (PTLD) in immunocompromised patients, as well as in many EBV-associated malignancies including Hodgkin's disease and nasopharyngeal carcinoma (NPC) (23,32,61,78,79).…”

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confidence: 99%

Epstein-Barr Virus LMP-1 Natural Sequence Variants Differ in Their Potential To Activate Cellular Signaling Pathways

Fielding

Sandvej

Mehl

et al. 2001

J Virol

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“…Because LMP1 plays a central role in the overall EBV strategy to suppress the cellular apoptotic program, we developed LMP1 antisense oligonucleotides that in EBV-infected B95.8 cells caused a substantial loss of LMP1 mRNA, a signi®cant decrease of LMP1 protein and a 50% inhibition of cell proliferation (Mattia et al, 1997).…”

mentioning

confidence: 99%

“…In order to evaluate whether suppression of the LMP1 gene by antisense DNA might a ect the expression of other EBV immortalizing genes, B95.8 cells were incubated with either the LMP1 antisense oligomer AS2 or with the control Sc2 oligonucleotide, a randomly scrambled version of the AS2 sequence (Mattia et al, 1997). Total RNA was isolated from untreated and oligonucleotide-treated cells and RT ± PCR experiments were performed for EBNA-2, EBNA-3A and EBNA-3C genes; in addition, RT ± PCR was carried out for EBNA-3B, as an EBV latent gene that lacks oncogenic potential, and for LMP1, to verify the e cacy of the antisense treatment.…”

mentioning

confidence: 99%

“…B95.8 cells, cultured to mid-log phase in RPMI medium supplemented with antibiotics and 2% (v/v) Biogro1 concentrated supplement (Biological Industries), were diluted in the same medium to 2.5610 5 /ml and seeded in 1.6 ml/well in 6-well plates. At 0, 24 and 48 h LMP1 antisense (AS2) and LMP1 non-sense (Sc2) oligodeoxynucleotides were added to a ®nal concentration of 20 mM (Mattia et al, 1997). After 54 h of incubation untreated (C) and oligomers-treated cells were harvested and total RNA puri®ed by RNeasy mini kit columns (Qiagen).…”

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confidence: 99%

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Antisense to Epstein Barr Virus-encoded LMP1 does not affect the transcription of viral and cellular proliferation-related genes, but induces phenotypic effects on EBV-transformed B lymphocytes

et al. 2002

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It is generally accepted that Epstein ± Barr virus (EBV) latent genes EBNA-2, EBNA-3A, -3C, EBNA-LP and LMP1 are essential for growth transformation and immortalization of B lymphocytes. Among these genes, LMP1 plays a key role in the survival and dissemination of the infected B cells by inducing anti-apoptotic genes and surface expression of several activation antigens and adhesion molecules. We have previously shown that antisense oligodeoxynucleotides directed to LMP1 mRNA, e ectively suppress LMP1 gene expression and substantially reduce B95.8 cell proliferation. In this study, we have used antisense LMP1 oligomers to investigate whether LMP1 suppression might in¯uence the expression of latent EBV genes with oncogenic potential, anti-apoptotic genes, or a ect the phenotype of EBV-infected B95.8 cells. Our data show that LMP1 suppression does not a ect the transcription of EBNA-2, EBNA-3A, -3B and -3C genes, or that of bcl-2 and mcl-1 anti-apoptotic genes. In contrast, consistent modi®ca-tions in the expression of CD39, CD54, CD23, CD11 and CD10 molecules were observed in B95.8 cells after treatment with antisense LMP1. Our ®ndings support the possibility for using LMP1 antisense oligomers as therapeutics in EBV-associated tumors.

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Inhibition of in vitro proliferation of Epstein Barr Virus infected B cells by an antisense oligodeoxynucleotide targeted against EBV latent membrane protein LMP1

Abstract: [No abstract available

Cited by 13 publications

References 10 publications

Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation

Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation

Epstein-Barr Virus LMP-1 Natural Sequence Variants Differ in Their Potential To Activate Cellular Signaling Pathways

Antisense to Epstein Barr Virus-encoded LMP1 does not affect the transcription of viral and cellular proliferation-related genes, but induces phenotypic effects on EBV-transformed B lymphocytes

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