Report

Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure

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Science  13 May 2010:
1187107
DOI: 10.1126/science.1187107

Abstract

Prions are infectious proteins composed of PrPSc, which induces conformational conversion of host-encoded PrPC to additional PrPSc. The mechanism underlying prion strain mutation in the absence of nucleic acids remains unresolved. Additionally, the frequency of strains causing chronic wasting disease (CWD), a burgeoning prion epidemic of cervids, is unknown. Using susceptible transgenic mice, we identified two prevalent CWD strains with divergent biological properties, but comprised of PrPSc with indistinguishable biochemical characteristics. While CWD transmissions indicated stable, independent strain propagation by elk PrPC, strain coexistence in the brains of deer and transgenic mice demonstrated unstable strain propagation by deer PrPC. The primary structures of deer and elk PrP differ at residue 226, which, in concert with PrPSc conformational compatibility, determines prion strain mutation in these cervids.