Abstract
AbstractUnconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans. The protein only hypothesis claims that the TSE agent is composed solely of the protein called prion (PrP^sc^)^1^. This protein is the misfolded form of a host-encoded cellular protein, PrP^c^ exerting presumably a vital role at the synapse^2^. Even though now widely accepted, the prion concept fails to provide in certain circumstances^3-6^, a satisfying interpretation of the infectious phenomenon. Using the 263K scrapie-hamster model, we conducted a transmission study to search for a putative prion-associated factor indispensable for infectivity. Here we show that innocuous recombinant prion protein (recPrP) was capable, in a reproducible manner, of transmitting scrapie disease when the protein was [beta]–sheet converted in a solution containing PrP^sc^-derived RNA material. Analysis of the PrP-RNA mixture revealed the association of recPrP with two prominent populations of small RNA molecules having an average length of about ~27 and ~55 nucleotides. We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrP^sc^).
Highlights
Unconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans
We show that innocuous recombinant prion protein was capable, in a reproducible manner, of transmitting scrapie disease when the protein was β–sheet converted in a solution containing PrPsc-derived RNA material
We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrPsc)
Summary
Unconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans. We show that innocuous recombinant prion protein (recPrP) was capable, in a reproducible manner, of transmitting scrapie disease when the protein was β–sheet converted in a solution containing PrPsc-derived RNA material. We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrPsc).
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