Environmental and host factors that contribute to prion strain evolution

Prions are novel pathogens that are composed entirely of PrP Sc , 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 PrP Sc . 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 naïve 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.