Abstract
More than 30 years ago PATTISON and MILLSON (1961) reported the occurrence of two distinct constellations of clinical signs, labeled nervous or drowsy, in goats experimentally infected with scrapie. These syndromes were reproducible through subsequent intracerebral inoculations, suggesting the existence of “true breeding” variants of scrapie agent. Subsequent transmissions of both goat and sheep scrapie into experimental rodents set the stage for isolation of multiple scrapie “strains” (ZLOTNIT 1965). The existence of scrapie isolates that exhibit distinct and stable properties in the same inbred mouse strain provided evidence for agent-specified information, thought to be encoded by a polynucleotide (BRUCE and DICKINSON 1987). The existence of microbiological strains of agent continues to be presented as an argument against the concept of a proteinaceous infectious particle devoid of functional nucleic acid. The only known functional component of prions is PrPSc, a disease-specific, posttranslational derivative of the normal prion protein isoform, PrPc (PRUSINER 1991). β-pleated sheet is a major secondary structure of PrPSc, in contrast to the predominance of α-helix in PrPc, and the two isoforms may differ only in their conformations (Pan et al. 1993; Safar et al. 1993). PrPSc is certainly necessary, and possibly sufficient, for transmission of scrapie. No scrapie-specific nucleic acid has ever been detected in purified prion preparations, and to be present at one molecule per infectious unit a prion-specific nucleic acid would need to have fewer than 50 nucleotides (Kellings et al. 1992). Properties of viral, bacteria and fungal strains are most often attributed directly to mutations within their nucleic acid genomes, with the interesting exception of prion-like epigenetic phenomena in yeast (WICKNER 1994). If prions are devoid of functional nucleic acid, other mechanisms must account for the existence of strains. The first part of this report emphasizes the role of PrP in determining strain properties, followed by discussion of other components that may be involved.
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Carlson, G.A. (1996). Prion Strains. In: Prusiner, S.B. (eds) Prions Prions Prions. Current Topics in Microbiology and Immunology, vol 207. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60983-1_4
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DOI: https://doi.org/10.1007/978-3-642-60983-1_4
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