Allelic Interference in Prion Replication Is Modulated by the Convertibility of the Interfering PrP(C) and Other Host-Specific Factors

Early studies in transgenic mouse lines have shown that the coexpression of endogenous murine prion protein (PrP(C)) and transgenic PrP(C) from another species either inhibits or allows the propagation of prions, depending on the infecting prion strain and interacting protein species. The way whereby this phenomenon, so-called “interference,” is modulated remains to be determined. In this study, different transgenic mouse lines were crossbred to produce mice coexpressing bovine and porcine PrP(C), bovine and murine PrP(C), or murine and porcine PrP(C). These animals and their respective hemizygous controls were inoculated with several prion strains from different sources (cattle, mice, and pigs) to examine the effects of the simultaneous presence of PrP(C) from two different species. Our results indicate interference with the infection process, manifested as extended survival times and reduced attack rates. The interference with the infectious process was reduced or absent when the potentiality interfering PrP(C) species was efficiently converted by the inoculated agent. However, the propagation of the endogenous murine PrP(Sc) was favored, allowing us to speculate that host-specific factors may disturb the interference caused by the coexpression of an exogenous second PrP(C).