CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease

Keith D Robertson, A. Manns, L. J. Swinnen, J. C. Zong, M. L. Gulley, R. F. Ambinder

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The Epstein-Barr virus (EBV) latency C promoter drives expression of a family of viral proteins commonly targeted by CD8 cytotoxic T cells. These proteins are not generally expressed in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. The failure to express these proteins is almost certainly an important factor in the evasion of immunosurveillance by EBV-associated tumors. In a previous study, we have shown that transcriptional activation of the C promoter is inhibited by methylation of a particular CpG site upstream of the promoter that prevents binding of a cellular protein (CBF2), and we have shown that this end adjacent CpG sites are methylated in a Burkitt's lymphoma cell line. In the present study, we show that CpG sites in the CBF2 binding region are predominantly methylated in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. In addition, we present the first direct evidence that the C promoter is transcriptionally silent in Burkitt's lymphoma. In contrast, we show a complete absence of methylation in the CBF2 binding region in a case of reversible EBV-associated B-cell lymphoma arising in an immunocompromised patient whose tumor shows C promoter transcriptional activity. By inhibiting expression of highly antigenic viral proteins, methylation of transcriptional control sequences may veil the presence of virus in tumor tissue from CD8(+) cytotoxic T-cell immune surveillance and thus facilitate viral tumorigenesis.

Original languageEnglish (US)
Pages (from-to)3129-3136
Number of pages8
JournalBlood
Volume88
Issue number8
StatePublished - Oct 15 1996
Externally publishedYes

Fingerprint

Virus Latency
Methylation
Burkitt Lymphoma
Human Herpesvirus 4
Hodgkin Disease
Viruses
Tumors
T-cells
Viral Proteins
Cells
T-Lymphocytes
Immunologic Monitoring
Oncogenic Viruses
Proteins
Immunocompromised Host
B-Cell Lymphoma
Transcriptional Activation
Neoplasms
Carcinogenesis
Chemical activation

ASJC Scopus subject areas

  • Hematology

Cite this

Robertson, K. D., Manns, A., Swinnen, L. J., Zong, J. C., Gulley, M. L., & Ambinder, R. F. (1996). CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease. Blood, 88(8), 3129-3136.

CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease. / Robertson, Keith D; Manns, A.; Swinnen, L. J.; Zong, J. C.; Gulley, M. L.; Ambinder, R. F.

In: Blood, Vol. 88, No. 8, 15.10.1996, p. 3129-3136.

Research output: Contribution to journalArticle

Robertson, KD, Manns, A, Swinnen, LJ, Zong, JC, Gulley, ML & Ambinder, RF 1996, 'CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease', Blood, vol. 88, no. 8, pp. 3129-3136.
Robertson KD, Manns A, Swinnen LJ, Zong JC, Gulley ML, Ambinder RF. CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease. Blood. 1996 Oct 15;88(8):3129-3136.
Robertson, Keith D ; Manns, A. ; Swinnen, L. J. ; Zong, J. C. ; Gulley, M. L. ; Ambinder, R. F. / CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease. In: Blood. 1996 ; Vol. 88, No. 8. pp. 3129-3136.
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