POTENT INHIBITION OF EPSTEIN-BARR-VIRUS BY PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES WITHOUT SEQUENCE SPECIFICATION

We found that 28-mer phosphorothioate oligodeoxynucleotides (S-oligos) with and without sequence specificity complementary to Epstein-Barr v irus (EBV) genes are potent inhibitors of EBV replication in cell cult ure. The decrease in the amount of EBV DNA, the activity of intracellu lar viral DNA polymerase, and virus production were dose dependent, wi th a 90% inhibitory dose of approximately 0.5 muM. No inhibition of ce ll growth was observed with the S-oligos at concentrations up to 20 mu M. The mechanism of action appears to be the inhibition of EBV DNA syn thesis. The reversibility of anti-EBV action is dependent on the dose and duration of drug exposure. S-oligos should be considered a new cla ss of anti-EBV agents.