Methylation patterns in intracellular Epstein-Barr virus (EBV) DNA sequences using the isoschizomers HpaII and MspI and the cloned EcoRI-J fragment as a probe have been studied. The possible role of DNA methylation in determining the producer and nonproducer status of EBV-carrying lymphoma cell lines and whether this pattern would be affected by treatment with inducers, like TPA and n-butyrate, which effectively activate the productive virus cycle in low-level producer lines, were examined. By studying intracellular EBV DNA present in total cellular DNA isolates it was concluded that (i) intracellular EBV DNA is methylated in and around the EcoRI-J fragment in both producer and nonproducer cell lines; (ii) methylation at this site is more pronounced in nonproducer cell lines as compared with producer cell lines; (iii) the cell lines studied here responded differently to chemical induction as determined by EBV-specific antigen immunofluorescence staining. However, no major differences in the methylation pattern in and around the EcoRI-J fragment could be observed before and after induction.
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