Enhancement of cellular protein synthesis sensitivity to diphtheria toxin by interferon

Abstract

In attempts to determine whether, by analogy to cholera and tetanus toxins, diphtheria toxin (DT) can also relieve the antiviral effect of interferon (IF), we found that it rather enhanced the inhibitory effect of IF on the replication of murine leukemia virus in chronically infected NIH/3T3 cells. This enhancement was found to be a consequence of an increased sensitivity to DT of cellular protein synthesis in IF-treated cells. IF stimulated the anti-protein synthesis activity of DT in both mouse cells that are known to be highly resistant to this toxin and in human HeLa cells that are highly sensitive to this toxin. This stimulation was dependent on IF dose. The effect of IF on DT action was strictly species specific, indicating that it was not a consequence of the mere binding of IF to the cell membrane, but rather reflected the cellular changes that followed this initial binding. IF was found to be capable of potentiating intact DT, but could not potentiate its fragments in any combination. IF did not have any effect on the in vitro nicotinamide adenine dinucleotide glycohydrolase activity of DT, suggesting that the effect of IF is not due to molecular modification of the toxin.