Transmissible spongiform encephalopathy agents also named prions are responsible for transmissible subacute spongiform encephalopathies (TSE) in humans and animals. Human transmissible spongiform encephalopathies are Creutzfeldt-Jakob Disease (CJD), Fatal Familial Insomnia, Kuru and Gerstmann-Straeussler-Scheinker syndrome. In animals, TSE are natural scrapie in sheep and goats, bovine spongiform encephalopathy, feline spongiforme encephalopathy, transmissible mink encephalopathy, and chronic wasting disease. The analysis of purified infectious fractions removed from infected brains are mostly composed of one host-coded protein, the prion protein (PrP), and free of any detectable specific nucleic acid~1. In vivo, the infectivity titre is always associated with a proportional accumulation of PrP. Aminoacid sequences of PrP obtained from normal and infected brains are identical, and these two proteins differ only by their biochemical and biophysical behaviour: in particular, PrP from TSE-affected individuals resists proteinase K digestion. PrP-c is the PrP found in normal individuals, PrP-res is the proteinase K resistant PrP identifiable in infected individuals. Moreover, PrP-res accumulation is never associated with an increase of PrP messenger RNAs: this accumulation is post-translational~2. Lastly, infected organisms accumulate their own PrP-res and not the PrP-res present in the inoculum. This data points out that infectivity is strongly associated with host-encoded PrP-res.
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