Environmental and host factors that contribute to prion strain evolution

Prions are novel pathogens that are composed entirely of PrPSc, the self-templating conformation of the host prion protein, PrP(C). Prion strains are operationally defined as a heritable phenotype of disease that are encoded by strain-specific conformations of PrPSc. The factors that influence the relative distribution of strains in a population are only beginning to be understood. For prions with an infectious etiology, environmental factors, such as strain-specific binding to surfaces and resistance to weathering, can influence which strains are available for transmission to a naive host. Strain-specific differences in efficiency of infection by natural routes of infection can also select for prion strains. The host amino acid sequence of PrP(C) has the greatest effect on dictating the repertoire of prion strains. The relative abundance of PrP(C), post-translational modifications of PrP(C) and cellular co-factors involved in prion conversion can also provide conditions that favor the prevalence of a subset of prion strains. Additionally, prion strains can interfere with each other, influencing the emergence of a dominant strain. Overall, both environmental and host factors may influence the repertoire and distribution of strains within a population.

Automated summary

Prions are novel pathogens composed of PrPSc, with strain distribution influenced by both environmental and host factors. The host amino acid sequence and post-translational modifications of PrP(C) play a critical role in dictating the repertoire of prion strains, and interference between prion strains may impact the emergence of dominant strains.