CpG methylation of viral DNA in EBV-associated tumours.
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.
Allday
M J
MJ
Department of Virology, Royal Postgraduate Medical School, London, UK.
Kundu
D
D
Finerty
S
S
Griffin
B E
BE
D000956:Antigens, Viral / Q000235:genetics; D015139:Blotting, Southern; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000032:analysis / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D008745:Methylation; D015183:Restriction Mapping; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism*
D000956:Antigens, Viral; D004279:DNA, Viral; D015226:Dinucleoside Phosphates; D019309:Epstein-Barr Virus Nuclear Antigens; C015772:CpG dinucleotide