NIH R01 · 2025
Contributions of prion strains and substrains to prion zoonotic potential and evolution
Prions are infectious protein-only zoonotic agents that can rapidly evolve in a new replication environment. Prion strains are encoded by strain-specific conformations of PrPSc, the infectious form of the host-encoded prion protein, PrPC. Collinge and Clarke hypothesized that prion strains are a mixture of a dominant prion strain and substrains. In support of this hypothesis, we and others have shown: i) treatment of prions with anti-prion drugs can result in the emergence of a drug resistant strain, ii) physical methods (e.g. thermostability) that partially inactivate prions can select for prions with altered strain properties, and iii) strains within a given host species can have…
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