Demethylation of the Epstein-barr virus origin of lytic replication and of the immediate early gene BZLF1 is DNA replication independent. Brief report

Arch Virol. 1999;144(11):2219-27. doi: 10.1007/s007050050636.


Epstein-Barr virus (EBV) episomal DNA is extensively methylated in Burkitt lymphoma derived cell lines. In this study we examined whether lytic viral cycle reactivation is dependent on demethylation of critical viral genes. Viral replication was induced in the Burkitt's lymphoma cell line Daudi by the combination of 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium-butyrate. Two regions necessary for EBV replication, the BZLF1 immediate early region and the origin of lytic cycle replication (ori Lyt) were demethylated during the early phase of the lytic virus cycle. Demethylation was observed while production of new (unmethylated) viral DNA was blocked by phosphonoformic acid (PFA). This suggests that demethylation, which may be instrumental for the onset of the lytic cycle, is an active process independent of viral DNA replication

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / biosynthesis
  • Antiviral Agents / pharmacology
  • Azacitidine / pharmacology
  • DNA Methylation* / drug effects
  • DNA Replication* / drug effects
  • DNA, Viral / drug effects
  • DNA, Viral / metabolism*
  • DNA-Binding Proteins / genetics*
  • Foscarnet / pharmacology
  • Herpesvirus 4, Human / drug effects
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Replication Origin* / drug effects
  • Trans-Activators / genetics*
  • Tumor Cells, Cultured
  • Viral Proteins / genetics*
  • Virus Replication* / drug effects


  • Antigens, Viral
  • Antiviral Agents
  • BZLF1 protein, Herpesvirus 4, Human
  • DNA, Viral
  • DNA-Binding Proteins
  • Epstein-Barr virus early antigen
  • Trans-Activators
  • Viral Proteins
  • Foscarnet
  • Azacitidine