Response of cultured mammalian cells to diphtheria toxin. V. Concurrent resistance to ribonucleic acid viruses in diphtheria toxin-resistant KB cell strains.

It was determined that KB-R cell strains, isolated from the KB cell line and resistant to diphtheria toxin, also resist infection by poliovirus, Mengo virus, vesicular stomatitis virus, and Newcastle disease virus. This resistance manifests itself by reduction in yields of progeny virus (a reduction of more than 2 logs in some cases), reduced production of viral-specific ribonucleic acid (RNA), and delayed cytopathic effect. In three KB-R strains tested, resistance was related to a step which falls between adsorption of virus and uncoating or release of viral messenger RNA. In two of these three strains, a second resistance mechanism was also active, causing a reduced production of viral-specific RNA. A relationship between the resistance to diphtheria toxin and the resistance to viral infection of the KB-R strains is considered. It has been postulated that the native diphtheria toxin molecule must be "activated" at the surface of a susceptible cell by a proteolytic process before it can enter the cell and inhibit protein synthesis. It is also known that the eclipse of some viruses occurs at or near the cell membrane and involves proteolytic activity. Resistance to viruses and toxin in the KB-R strains may result from the loss or modification of related labilizing or activating principles associated with the surface receptors for these agents.