Plasmid DNA as a possible state of Epstein-Barr virus genomes in nonproductive cells.

It has been shown that the EBV DNA in Raji cells is located in chromosomes and that most of this EBV DNA can be separated from high molecular weight cell DNA both in alkaline and neutral glycerol gradients. The data indicate that the latent EBV DNA may exist possibly as a plasmid DNA. As 50 genomes of EBV DNA are equal to 0.1% of the total cell DNA, it may be quite conceivable that such an amount of DNA should remain in a non-integrated form. Chromosomal location may be a requisite for any DNA to persist in the nucleus of cells and to be divided into daughter cells evenly. As the present studies measured only the status of the major portion of EBV genomes in Raji cells, a possibility still remains that a few genomes of EBV may be linearly integrated into cell DNA and these may be responsible for cellular transformation. Another possibility that a small piece of cellular DNA might be attached to EBV DNA in Raji cells, which might serve as a control signal for replication and/or transcription of the latent virust DNA, has also not been ruled out. Even though EBV DNA is not integrated covalently into cell DNA, the association of the virus genomes with cells is very stable and the number of EBV genomes remains unchanged throughout many cell generations. In synchronized cells, all EBV genomes replicate simultaneously at an early S phase before maximum synthesis of cell DNA replication occurs (Hamper et al. 1974). This indicates that EBV DNA in a plasmid state is strictly under a cellular control mechanism. How this latent virus DNA is controlled in cells will be examined in future studies.