Quantifying the sequence-dependent species barrier between hamster and mouse prions

Prion diseases are transmissible neurodegenerative disorders. It is widely accepted that prions are the infectious agents responsible for disease transmission, and the sequence homology between the infectious prion and the host prion protein determines its transmission efficiency across species. However, previous studies have often reported different results regarding seeding efficiency, the efficiency of initiating amyloid propagation by adding pre-existing amyloid fibrils as seed. In the present study, we used synthetic peptides as a simple system to determine the sequence-dependent transmission barrier between hamster and mouse. We found that the heterologous seeding efficiency of hamster and mouse prion peptides was 4 times less than that of homologous seeding. Moreover, residue 139 was not the only residue in determining seeding efficiency. When the seed had Ile at this position, the homology at this position between seed and monomer determined the seeding efficiency. When the seed had Met at this position, homology at residues 109 and 112 determined the seeding efficiency.