CpG methylation of viral DNA in EBV-associated tumours

Int J Cancer. 1990 Jun 15;45(6):1125-30. doi: 10.1002/ijc.2910450623.


In EBV-immortalized lymphoblastoid cell lines (LCLs) a small number of "latent" proteins are expressed. These are the EBV nuclear antigens, EBNAs 1-6, and a latent membrane protein, LMP. We have investigated the expression of these proteins in a variety of EBV-associated tumours and cell lines. Whereas transplant and B-cell lymphomas from cotton-top tamarins appear to express the full range of antigens found in LCLs, we and others have found that in Burkitt's lymphomas (BL) and a nasopharyngeal carcinoma (NPC) isolate, EBNA expression is restricted to EBNA-I. (In NPC, but not in BL, LMP may also be expressed). In order to ask what restricts the expression of EBNA 2-6 in NPC and BL cells it seemed reasonable to consider the possibility that the DNA sequences normally regulating expression of these antigens could be chemically modified. In this analysis, a tight inverse correlation between methylation of CpG dinucleotides in the 5' flanking region of the EBNA-2 gene and the expression of EBNAs 2-6 has been revealed. In the NPC tumour, CpG methylation within the gene is also observed, as is specific methylation over the EBNA-I region I and II binding sites (in oriP). The significance of these observations is considered.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / genetics
  • Blotting, Southern
  • Cell Line
  • DNA, Viral / analysis
  • DNA, Viral / metabolism*
  • Dinucleoside Phosphates / analysis
  • Dinucleoside Phosphates / metabolism*
  • Epstein-Barr Virus Nuclear Antigens
  • Gene Expression Regulation, Viral / physiology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunoblotting
  • Methylation
  • Restriction Mapping
  • Tumor Cells, Cultured / metabolism
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / metabolism*


  • Antigens, Viral
  • DNA, Viral
  • Dinucleoside Phosphates
  • Epstein-Barr Virus Nuclear Antigens
  • cytidylyl-3'-5'-guanosine