Antibodies to the Epstein-Barr virus transactivator protein (ZEBRA) as a valuable biomarker in young patients with nasopharyngeal carcinoma

Dardari, Rkia; Khyatti, Meriem; Benider, Abdellatif; Jouhadi, H.; Kahlain, A; Cochet, C; Mansouri, Aziz; Gueddari, B.K. El; Benslimane, A.; Joab, Irène

doi:10.1002/(sici)1097-0215(20000401)86:1<71::aid-ijc11>3.0.co;2-1

Cited by 58 publications

(45 citation statements)

References 18 publications

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“…In the cancer screening setting, the sensitivity, specificity, quality control, and costs are relevant considerations. To date, only a few markers or marker panels have been reported to have both a sensitivity and specificity Ͼ90% for detection of NPC (15,17,18,36 ). The sensitivity of 99% of the combined IgA-VCA/EBV DNA marker panel and the specificity of 96 -98% of the respective markers in the present study warrant further studies in the screening setting.…”

Section: Discussionmentioning

confidence: 99%

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Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein–Barr Virus DNA and Anti-Epstein–Barr Viral Capsid Antigen IgA Antibody

Leung¹,

Tam²,

Chan³

et al. 2004

Clinical Chemistry

101

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Section: Discussionmentioning

confidence: 99%

“…These were based on antibodies to different antigenic components of the EBV (9,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Attempts to use panels of antibody-based markers have generally been useful in improving the accuracy of NPC detection (13, 15, 20, 21, 29 -32 ).…”

mentioning

confidence: 99%

Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein–Barr Virus DNA and Anti-Epstein–Barr Viral Capsid Antigen IgA Antibody

Leung¹,

Tam²,

Chan³

et al. 2004

Clinical Chemistry

101

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“…Lytic infection is observed at high rates in patients with oral hairy leukoplakia and EBV-positive gastric carcinoma (19,22,29). Elevated levels of EBV lytic antigens are a prognostic risk factor for nasopharyngeal carcinoma in regions of endemicity (13). Lytic cycle gene expression or replication is also required for lymphomagenesis in SCID mouse models (20,21).…”

mentioning

confidence: 99%

Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication

Wiedmer

Wang

Zhou

et al. 2008

J Virol

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Disruption of cellular metabolic processes and usurpation of host proteins are hallmarks of herpesvirus lytic infection. Epstein-Barr virus (EBV) lytic replication is initiated by the immediate-early protein Zta. Zta is a multifunctional DNA binding protein that stimulates viral gene transcription, nucleates a replication complex at the viral origin of lytic replication, and inhibits cell cycle proliferation. To better understand these functions and identify cellular collaborators of Zta, we purified an epitope-tagged version of Zta in cells capable of supporting lytic replication. FLAG-tagged Zta was purified from a nuclear fraction using FLAG antibody immunopurification and peptide elution. Zta-associated proteins were isolated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and identified by mass spectrometry. The Zta-associated proteins included members of the HSP70 family and various single-stranded DNA and RNA binding proteins. The nuclear replication protein A subunits (RPA70 and RPA32) and the human mitochondrial single-stranded DNA binding protein (mtSSB) were confirmed by Western blotting to be specifically enriched in the FLAG-Zta immunopurified complex. mtSSB coimmunoprecipitated with endogenous Zta during reactivation of EBVpositive Burkitt lymphoma and lymphoblastoid cell lines. Small interfering RNA depletion of mtSSB reduced Zta-induced lytic replication of EBV but had only a modest effect on transcription activation function. A point mutation in the Zta DNA binding domain (C189S), which is known to reduce lytic cycle replication, eliminated mtSSB association with Zta. The predominantly mitochondrial localization of mtSSB was shifted to partly nuclear localization in cells expressing Zta. Mitochondrial DNA synthesis and genome copy number were reduced by Zta-induced EBV lytic replication. We conclude that Zta interaction with mtSSB serves the dual function of facilitating viral and blocking mitochondrial DNA replication.

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“…These include Burkitt's lymphoma (24,25), some cases of Hodgkin's disease (1,24), nasopharyngeal carcinoma (9) and gastric carcinoma (reference 46 and references cited therein). However, lytic replication of EBV may also be associated with human diseases in addition to infectious mononucleosis, with the presence of antibodies to EBV lytic antigens correlating with increased risk for nasopharyngeal carcinoma (7) and hairy leukoplakia (3,48,49,53).…”

mentioning

confidence: 99%

ZEB Negatively Regulates the Lytic-Switch BZLF1 Gene Promoter of Epstein-Barr Virus

Kraus

Perrigoue

Mertz

2003

J Virol

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Epstein-Barr virus (EBV) is a human herpesvirus capable of establishing a latent state in B lymphocytes.The product of the immediate-early BZLF1 gene, Zta, is a transcriptional transactivator essential for viral DNA amplification and virion production. Previously, we identified a negative cis-acting element within the BZLF1 promoter termed ZV. ZV contains the sequence 5-CAGGTA-3 located at nucleotides ؊17 to ؊12 relative to the transcription initiation site. It sequence specifically binds a cellular factor, ZVR. Based on sequence binding specificity, we postulated that ZVR may be zinc finger E-box binding factor (ZEB) or a related zinc finger/homeodomain family member. We show here by immunoshift assays that ZVR and human ZEB specifically cross-react with an antibody to ␦EF1, the chicken homolog of ZEB. Competition electrophoretic mobility shift assays confirmed that ZEB binds to the ZV element with the same binding specificity as ZVR. Overexpression of ZEB in either B-lymphocytic DG75 cells or mammary epithelial MCF-7 cells repressed Zta-induced activation of the BZLF1 promoter four-to fivefold via the ZV site. Thus, we conclude that the previously identified cellular repressor ZVR is, in fact, ZEB. We also present evidence that other cellular factors likely affect the transcriptional activity of ZEB. Lastly, we identify a ZEB-binding site within the promoter of the lytic BRLF1 gene of EBV. We postulate that ZEB likely plays an important role in regulating the life cycle of EBV. Epstein-Barr virus (EBV) is a human gammaherpesvirus estimated to infect 90% of the world's population (24, 25).Primary infection and replication of the virus are thought to occur in the oropharyngeal epithelium (24,25,30,45). EBV can also infect B lymphocytes, where it establishes a latent infection (1,26,40). Latent infection by EBV is associated with a number of malignancies. These include Burkitt's lymphoma (24, 25), some cases of Hodgkin's disease (1, 24), nasopharyngeal carcinoma (9) and gastric carcinoma (reference 46 and references cited therein). However, lytic replication of EBV may also be associated with human diseases in addition to infectious mononucleosis, with the presence of antibodies to EBV lytic antigens correlating with increased risk for nasopharyngeal carcinoma (7) and hairy leukoplakia (3,48,49,53).Once EBV has established a latent infection, only a small subset of EBV's approximately 100 genes are expressed: EBVencoded early antigens (EBNAs) 1 to 6, latent membrane proteins (LMP) 1 and 2, two EBV-encoded small nuclear RNAs, and the BamHIA transcripts (24, 25). The expression of a subset of these genes is sufficient to immortalize B cells and maintain the viral genome as an episome (27). However, reactivation of the viral lytic phase can occur, resulting in replication of the viral genome to a higher copy number and production of infectious virions. Treatment of certain viralgenome-harboring B cells and epithelial cells with chemical reagents (4,12,23,33,56), serum factors (2), transforming growth factor ␤1 (15),...

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Antibodies to the Epstein-Barr virus transactivator protein (ZEBRA) as a valuable biomarker in young patients with nasopharyngeal carcinoma

Cited by 58 publications

References 18 publications

Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein–Barr Virus DNA and Anti-Epstein–Barr Viral Capsid Antigen IgA Antibody

Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein–Barr Virus DNA and Anti-Epstein–Barr Viral Capsid Antigen IgA Antibody

Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication

ZEB Negatively Regulates the Lytic-Switch BZLF1 Gene Promoter of Epstein-Barr Virus

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