Environmentally-relevant forms of the prion protein

Area of Science:

• Veterinary Neurology
• Environmental Microbiology
• Biochemistry

Background:

• Scrapie and chronic wasting disease (CWD) are environmentally persistent prion diseases.
• The N-terminus of the infectious prion protein (PrPSc) is implicated in soil sorption.
• Prion degradation in carcasses may influence environmental transmission pathways.

Purpose of the Study:

• To investigate the hypothesis that proteinases cleave the N-terminus of PrPSc in prion-infected animal carcasses.
• To assess the degradation of PrPSc in different prion disease models under controlled temperature conditions.

Main Methods:

• Incubation of hamster (HY TME), transgenic mouse (CWD), and elk (CWD) brain homogenates at 22°C and 37°C for up to 35 days.
• Western blot analysis using N-terminal and middle region anti-PrP monoclonal antibodies to detect PrPSc degradation.

Main Results:

• Full-length PrPSc showed faint or undetectable N-terminal signals after 35 days across all tested systems and temperatures.
• N-terminal degradation of PrPSc was observed in hamster, transgenic mouse, and elk brain homogenates.
• Chronic wasting disease PrPSc in mouse and elk models exhibited greater degradation resistance compared to HY TME PrPSc.

Conclusions:

• Full-length PrPSc may be less prevalent in animal carcasses than previously assumed.
• Environmental prion studies should account for N-terminal-degraded PrPSc in addition to the full-length form.
• The transgenic mouse-CWD model serves as a suitable surrogate for natural CWD prions regarding environmental fate.