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.
KeywordsDMSO Agarose Electrophoresis Hydrolase Alan
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