Abstract
Prion diseases are zoonotic transmissible neurodegenerative disorders of animals, including humans. The causative agent is PrPSc, a misfolded isomer of the normal cellular prion protein, PrPC. Prions can persist in the environment after adsorption to surfaces including soils, feeding troughs, or fences. In naturally occurring prion disease, multiples strains have been identified and can co-exist in an individual host. Strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in emergence of new strains in a population. It is unknown how environmental factors can influence prion strain emergence. We hypothesize that enzymatic degradation, surface adsorption, and natural weathering can alter prion strain emergence from a mixture.|We used proteinase K (PK) to selectively alter the ratio of HY and DY PrPSc. Extensive PK digestion of HY and DY PrPSc resulted in a relatively greater reduction of DY PrPSc compared to HY PrPSc. Use of the PK digested material in protein misfolding cyclic amplification strain interference (PMCAsi) resulted in an earlier emergence of HY PrPSc compared to undigested controls. This result established that strain-specific alteration of the starting ratios of conversion competent HY and DY PrPSc by can alter strain emergence.|We then investigated whether environmentally relevant factors such as surface binding and weathering could alter strain emergence. Adsorption of HY and DY PrPSc to silty clay loam (SCL) both separately and together, did not alter strain emergence compared to unbound control PMCAsi reactions. Similarly, we found that repeated cycles of wetting and drying of HY and DY PrPSc bound to SCL did not alter the emergence of HY PrPSc compared to untreated control reactions. Interestingly, we found that drying of adsorbed protein to SCL could restore its ability to interfere with the emergence of HY, identifying a novel strain interference mechanism. Drying protein to SCL could “recharge” the surface for further adsorption, providing a potential mechanism for the observed interference effect. This data indicates that prion strain interference can occur when bound to surfaces and is of high significance since surface bound prions exposed to weathering may play an important role in natural transmission.