Azidothymidine inhibits NF-κB and induces Epstein-Barr virus gene expression in Burkitt lymphoma

Kurokawa, Masami; Ghosh, Subrata; Ramos, Juan Carlos; Mian, A. Mohsin; Toomey, Ngoc L.; Cabral, Lisa; Whitby, Denise; Barber, Glen N.; Dittmer, Dirk P.; Harrington, William J.

doi:10.1182/blood-2004-09-3748

Cited by 50 publications

(41 citation statements)

References 23 publications

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“…BL-5 and BL-8 cells are primary cultures derived from patients with AIDS-related EBV + BL. The tumors carry the typical t8:14 c-MYC translocation (13). A lymphoblastoid derivative (BL-5R) was obtained after serially passaging BL-5 cells over a 4-to 5-week period.…”

Section: Methodsmentioning

confidence: 99%

EBV MicroRNAs in Primary Lymphomas and Targeting of CXCL-11 by ebv-mir-BHRF1-3

et al. 2008

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EBV-encoded microRNAs (miRNAs) have been identified and their functions are being studied. The expression pattern of these miRNAs in clinical samples of EBV-associated nonHodgkin's lymphomas is unknown. We analyzed five primary ''endemic'' pediatric Burkitt's lymphomas (BL), two acquired immunodeficiency syndrome (AIDS)-related type I latency BL lines, a type III latency line, three EBV + primary effusion lymphomas (PEL), and three AIDS-related diffuse large B-cell lymphomas (DLBCL) for expression of EBV-encoded miRNAs.

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Section: Methodsmentioning

confidence: 99%

EBV MicroRNAs in Primary Lymphomas and Targeting of CXCL-11 by ebv-mir-BHRF1-3

et al. 2008

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“…Real-time qRT-PCR arrays containing PCR primers targeting all ORFs of the EBV genome were designed and performed as previously described (23). RNA used in the microarray analysis was coimmunoprecipitated and purified as described above.…”

Section: Methodsmentioning

confidence: 99%

General and Target-Specific RNA Binding Properties of Epstein-Barr Virus SM Posttranscriptional Regulatory Protein

Han

Verma

Hilscher³

et al. 2009

J Virol

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Epstein-Barr virus (EBV) SM protein is an essential nuclear shuttling protein expressed by EBV early during the lytic phase of replication. SM acts to increase EBV lytic gene expression by binding EBV mRNAs and enhancing accumulation of the majority of EBV lytic cycle mRNAs. SM increases target mRNA stability and nuclear export, in addition to modulating RNA splicing. SM and its homologs in other herpesvirus have been hypothesized to function in part by binding viral RNAs and recruiting cellular export factors. Although activation of gene expression by SM is gene specific, it is unknown whether SM binds to mRNA in a specific manner or whether its RNA binding is target independent. SM-mRNA complexes were isolated from EBVinfected B-lymphocyte cell lines induced to permit lytic EBV replication, and a quantitative measurement of mRNAs corresponding to all known EBV open reading frames was performed by real-time quantitative reverse transcription-PCR. The results showed that although SM has broad RNA binding properties, there is a clear hierarchy of affinities among EBV mRNAs with respect to SM complex formation. In vitro binding assays with two of the most highly SM-associated transcripts suggested that SM binds preferentially to specific sequences or structures present in noncoding regions of some EBV mRNAs. Furthermore, the presence of these sequences conferred responsiveness to SM. These data are consistent with a mechanism of action similar to that of hnRNPs, which exert sequence-specific effects on gene expression despite having multiple degenerate consensus binding sites common to a large number of RNAs.Epstein-Barr virus (EBV) SM is an RNA binding protein that is essential for lytic EBV replication (1,5,6,8,14,15,17,(33)(34)(35)42). The SM gene is homologous to immediate-early or early genes expressed by several other human and animal herpesviruses, including those encoding herpes simplex virus type 1 (HSV-1) ICP27, human cytomegalovirus (HCMV) UL69, varicella-zoster virus open reading frame 4 (ORF4) protein, and Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein/Mta (2,24,27,30,36,47). These proteins are multifunctional and function as transcriptional and posttranscriptional regulators of gene expression. One of the major roles of SM is to enhance EBV gene expression by increasing the accumulation of lytic EBV transcripts (5, 21, 39). In experiments performed with cells infected with recombinant EBV with SM deleted, exogenous expression of SM increased the expression of more than 50% of lytic EBV transcripts (15). Most of these SM-responsive transcripts accumulate poorly in the absence of SM. The dependence of these mRNAs on SM is multifactorial, as lytic EBV DNA replication also requires SM, primarily due to SM-enhanced expression of EBV DNA polymerase and primase proteins (15). Thus, SM may stimulate lytic EBV gene expression indirectly, by enhancing lytic EBV replication, as well as by having direct effects on target mRNAs. SM is thought to bind to EBV mRNAs in the nucleus and to enhance mRNA e...

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“…Methods for nuclear protein extraction and EMSA supershift analyses in our laboratory have been described previously. 34 …”

Section: Electrophoretic Mobility Shift Assaysmentioning

confidence: 99%

“…Protein sample preparation and Western blot analysis were performed as previously described. 34 Total protein (25-50 g) was fractionated on 12% SDS-PAGE and transferred by electroblotting onto nitrocellulose membrane (Bio-Rad Laboratories, Hercules, CA). Proteins were visualized with the enhanced chemiluminescence (ECL) developing kit (Amersham, Piscataway, NJ).…”

Section: Western Blot Analysismentioning

confidence: 99%