Alteration of prion strain emergence by nonhost factors

Prions can persist in the environment for extended periods of time after adsorption to surfaces, including soils, feeding troughs, or fences. Prion strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in strain maintenance or emergence of new strains in a population. Extensive proteinase K (PK) digestion of Hyper (HY) and Drowsy (DY) PrP^Sc resulted in a greater reduction in the level of DY PrP^Sc than of HY PrP^Sc. Use of the PKdigested material in protein misfolding cyclic amplification strain interference (PMCAsi) resulted in earlier emergence of HY PrP^Sc than of undigested controls. This result established that strain-specific alteration of the starting ratios of conversioncompetent HY and DY PrP^Sc can alter strain emergence. We next investigated whether environmentally relevant factors such as surface binding and weathering could alter strain emergence. Adsorption of HY and DY PrP^Sc to silty clay loam (SCL), both separately and combined, resulted in DY interfering with the emergence of HY in PMCAsi in a manner similar to that seen with unbound controls. Similarly, repeated cycles of wetting and drying of SCL-bound HY and DY PrP^Sc did not alter the emergence of HY PrP^Sc compared to untreated controls. Importantly, these data indicate that prion strain interference can occur when prions are bound to surfaces. Interestingly, we found that drying of adsorbed brain homogenate on SCL could restore its ability to interfere with the emergence of HY, suggesting a novel strain interference mechanism. Overall, these data provide evidence that the emergence of a strain from a mixture can be influenced by nonhost factors.