Porcine prion protein amyloid

Area of Science:

• Prion biology
• Zoonotic diseases
• Mammalian protein misfolding

Background:

• Mammalian prions are misfolded prion protein (PrP) aggregates with amyloid features.
• Prions are zoonotic agents affecting various mammals, with bovine spongiform encephalopathy (BSE) known to infect humans.
• Other species in the food chain (sheep, goat, elk, deer) and pets (cats, dogs) have varying susceptibility, while pigs are largely resistant.

Purpose of the Study:

• To investigate the in vitro amyloidogenicity and cross-seeding potential of prion protein (PrP) from various mammalian species.
• To assess the potential for pigs, despite their resistance to prion diseases, to act as silent carriers of infectious prions.

Main Methods:

• Biochemical, biophysical, and neurobiological characterization of PrPs from different mammalian species.
• In vitro studies examining generic amyloidogenicity and cross-seeding fibril formation activity of various mammalian PrPs on human PrP.

Main Results:

• All studied mammalian PrPs demonstrated generic amyloidogenicity in vitro.
• Evidence suggests cross-seeding fibril formation activity of all tested PrPs on the human PrP sequence, irrespective of the species' prion disease susceptibility.
• Porcine PrP was among those studied for amyloidogenicity.

Conclusions:

• The in vitro findings suggest a universal amyloidogenic potential and cross-seeding capability among mammalian PrPs.
• Despite pigs' general resistance to prion diseases, their potential role as clinically silent carriers of replicating prions warrants further investigation due to their significant presence in the human food chain.