Minor prion substrains overcome transmission barriers.

Area of Science:

• Neuroscience
• Infectious Diseases
• Molecular Biology

Background:

• Mammalian prion diseases stem from misfolded prion proteins (PrP^Sc).
• Prions are thought to comprise dominant and minor strains.
• The role of minor prion strains in species barrier crossing is largely unknown.

Purpose of the Study:

• To investigate the contribution of minor prion strains to interspecies transmission.
• To compare the infectivity and host range of minor prion strains versus the dominant DY TME strain.
• To assess the diversity and zoonotic potential of minor prion strains.

Main Methods:

• Isolation of minor prion strains from biologically cloned DY TME.
• Infection efficiency assays using rabbit kidney epithelial cells expressing hamster PrP^C.
• Protein misfolding cyclic amplification (PMCA) to assess conversion of mouse PrP^C.

Main Results:

• Minor prion strains exhibited higher infection efficiency than the dominant DY TME strain.
• Dominant DY TME failed to convert mouse PrP^C, while minor strains did so robustly.
• Significant differences in PMCA conversion efficiency were observed among minor strains and HY TME.

Conclusions:

• Minor prion strains play a significant role in crossing the species barrier.
• The diversity of minor prion strains may be greater than previously recognized.
• These findings have implications for understanding prion zoonotic potential.