Strains of CHO-K1 cells resistant to Pseudomonas exotoxin A and cross-resistant to diphtheria toxin and viruses

Abstract

We have investigated two phenotypically distinct types of mutants of CHO-K1 cells that are resistant to Pseudomonas exotoxin A due to a defect in the delivery of active toxin to the target site in the cell, elongation factor 2. Both types contain normal levels of toxin-sensitive elongation factor-2. Hybridization studies have shown that these cells fall into two distinct complementation groups. One group, designated DPVr, is resistant to Pseudomonas toxin, diphtheria toxin, and four enveloped RNA viruses. This group is also hypersensitive to ricin. The resistance of this group is apparently related to a defect in a mechanism for the acidification of endocytic vesicles. The other group, designated PVr, is resistant to Pseudomonas toxin and to three enveloped RNA viruses. The resistance of this group appears to be related to a defect in a cellular mechanism required for the maturation of Sindbis virus that is likewise required for the entry of active Pseudomonas toxin.