Strain-Dependent Susceptibility to Prion Infection Encoded by Arg171 and Lys176 Sheep Prion Protein Polymorphic...

Area of Science:

• Veterinary Medicine
• Neuroscience
• Molecular Biology

Background:

• Classical scrapie in sheep is caused by multiple strains, unlike epidemic classical bovine spongiform encephalopathy (BSE).
• Sheep prion protein (PrP) polymorphisms R171 and K176 in the β2-α2 loop region are linked to protection against classical scrapie.
• Understanding these polymorphisms is crucial for managing prion diseases in livestock.

Purpose of the Study:

• To investigate the protective role of R171 and K176 sheep PrP variants against different prion strains.
• To assess the susceptibility and resistance of transgenic mouse models expressing these variants to various prion isolates.
• To determine the utility of these variants in distinguishing between different prion strains.

Main Methods:

• Generation of transgenic mouse lines (R171-Tg552 and K176-Tg570) expressing specific sheep PrP polymorphic variants.
• Intracranial challenge of these mouse lines with a panel of diverse prion strains, including classical scrapie and BSE isolates.
• Characterization of prion propagation and disease progression in the transgenic mice.

Main Results:

• Both R171 and K176 mouse lines showed high susceptibility and long survival times with atypical scrapie isolates.
• Classical scrapie isolates were completely blocked in R171-Tg552 mice and largely restricted in K176-Tg570 mice.
• BSE transmission was only successful in R171-Tg552 mice after adaptation, while K176-Tg570 mice remained resistant even after passage in sheep.

Conclusions:

• The R171 and K176 polymorphic variants of ovine PrP restrict prion propagation in a strain-dependent manner.
• These variants serve as valuable tools for the discrimination of prion strains.
• The findings have implications for understanding prion disease pathogenesis and developing diagnostic strategies.