In vivo growth of Epstein-Barr virus transformed B cells with mutations in latent membrane protein 2 (LMP2)

Rochford, Rosemary; Miller, Cheryl L.; Cannon, Martin J.; Izumi, Kenneth M.; Kieff, Elliott; Longnecker, Richard

doi:10.1007/s007050050113

Cited by 15 publications

(12 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have addressed whether LMP2A promotes the expansion of LCLs in vivo (26). Findings from this study indicate that LMP2A Ϫ LCLs showed no defect in expansion in SCID mice, demonstrating that LMP2A is not important for the expansion of EBV-transformed B cells in this model.…”

Section: Discussionmentioning

confidence: 59%

Epstein-Barr Virus LMP2A Enhances B-Cell Responses In Vivo and In Vitro

Swanson‐Mungerson

Bultema

Longnecker

2006

J Virol

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 59%

Epstein-Barr Virus LMP2A Enhances B-Cell Responses In Vivo and In Vitro

Swanson‐Mungerson

Bultema

Longnecker

2006

J Virol

View full text Add to dashboard Cite

show abstract

“…However, our immunohistochemical analysis indicates that LMP-1 is expressed only by a subset of EBVϩ B cells, which suggests that LMP-1 may not be critical for growth of the PTLD-like cells and their sensitivity to RAD. EBV also encodes two other, related membrane proteins, LMP-2A and LMP-2B, but they also do not seem to be essential for in vivo growth of EBVϩ B cells (40). Alternatively, RAD might inhibit signaling mediated by cytokines induced by EBV in the target cells, such as tumor necrosis factor-␣ and tumor necrosis factor-␤ (34).…”

Section: Discussionmentioning

confidence: 99%

The immunosuppressive macrolide RAD inhibits growth of human Epstein–Barr virus-transformed B lymphocytes in vitro and in vivo : A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders

Majewski

Korecka

Kossev

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

207

139

View full text Add to dashboard Cite

“…Because most tissue-specific cellular genes and viral genes contain TATA elements as well as enhancer factor binding sites, this approach may be generally applicable for the inhibition of most target genes. (41,42). PBMCs were cultured and either were left untreated or were treated with 10 M polyamides 1 ϩ 3 or 2 ϩ 4 for six days.…”

Section: Fig 4 Polyamide Inhibition Of Hiv-1 Replicationmentioning

confidence: 99%

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Dickinson

Gulizia

Trauger

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

226

177

View full text Add to dashboard Cite

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.Simple rules have been developed to rationally control the sequence specificity of minor-groove binding polyamides containing pyrrole (Py) and imidazole (Im) amino acids (1-6). DNA recognition depends on a code of side-by-side aromatic amino acid pairings in the minor groove. A pyrrole opposite an imidazole (Py͞Im pairing) targets a C⅐G bp whereas Im͞Py targets a G⅐C bp. A Py͞Py pair binds both A⅐T and T⅐A pairs. These compounds represent the only class of synthetic small molecules that can bind predetermined DNA sequences with affinities and specificities comparable to DNA-binding proteins (7). The DNA-binding activity of the 5S RNA genespecific transcription factor TFIIIA was inhibited by an eightring hairpin polyamide that bound within the recognition site of zinc finger four in the DNA minor groove. As a result, transcription of 5S RNA genes by RNA polymerase III was suppressed in vitro and in cultured Xenopus cells (8). The question arises whether polyamides can permeate human cells and specifically regulate genes transcribed by pol II (RNA polymerase II). As a first case study, we examined the ability of polyamides to inhibit HIV type 1 (HIV-1) transcription in cell-free assays and viral replication in human lymphocytes.The HIV-1 enhancer͞promoter element contains binding sites for the cell-encoded proteins upstream stimulatory factor, Ets-1, lymphoid-enhancer binding factor 1 (LEF-1) the nuclear factors NF-B, Sp1, and TATA-box binding protein (TBP) (Fig. 1 A) (9). To shut-down the promoter, polyamides were designed to target the transcription factors TBP, LEF-1, and Ets-1 simultaneously. TBP is indispensable for initiation of HIV-1 transcription, and LEF-1, considered to be an architectural protein, plays a central role in coordinating activities of multiple transcription factors (10). Both TBP and LEF-1 bind the minor groove of DNA and are likely to be inhibited by the minor groove binding polyamides. Ets-1 predominantly contacts the major groove in the center of its binding site, with additional flanking contacts that are possibly in the m...

show abstract

In vivo growth of Epstein-Barr virus transformed B cells with mutations in latent membrane protein 2 (LMP2)

Cited by 15 publications

References 45 publications

Epstein-Barr Virus LMP2A Enhances B-Cell Responses In Vivo and In Vitro

Epstein-Barr Virus LMP2A Enhances B-Cell Responses In Vivo and In Vitro

The immunosuppressive macrolide RAD inhibits growth of human Epstein–Barr virus-transformed B lymphocytes in vitro and in vivo : A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Contact Info

Product

Resources

About