Effects of S-adenosylhomocysteine and Analogs on Epstein-Barr Virus (EBV)-Induced Transformation, EBV DNA Methylation and Gene Expression
EBV DNA becomes increasingly methylated with time following cell transformation (1) while hypomethylation has been associated with expression of viral genes (2). S-adenosylhomocysteine (SAH), a product of the S-adenosylmethionine transmethylation reaction, acts as a competitive inhibitor of DNA methyltransferases (3). In the present study SAH and analogs, sinefungin (SF) and 5′-deoxy-5′-S-isobutyladenosine (SIBA), as well as 5-azacytidine, which inhibits methylation of nascent DNA (4), were utilized in studies to determine the role of DNA methylation in the regulation of Epstein-Barr virus (EBV) functions such as transformation of human peripheral blood lymphocytes (PBL) and gene expression in lymphoblastoid cell lines. SF and SIBA, but not SAH, inhibited EBV-induced transformation of human PBLs. Indirect immunofluorescence and flow cytometric analyses revealed a significant increase in viral capsid antigen expression in lymphoblastoid cell lines following exposure to the analogs SF and SIBA, but not SAH.
KeywordsLymphoblastoid Cell Line Human Peripheral Blood Lymphocyte Transmethylation Reaction Human PBLs HpaII Digestion
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