THE ASSOCIATION BETWEEN PRP AND INFECTIVITY IN SCRAPIE AND BSE INFECTED-MOUSE BRAIN

The structure of the scrapie agent remains unknown. However, scrapie i nfectivity tends to co-sediment with an infection specific fraction of the glycoprotein PrP (PrPSc) under conditions which solubilise the no rmal form of this protein (PrPc); accordingly, PrP has been proposed a s a candidate component of the agent. To investigate this further we h ave been examining a new scrapie-related murine model in conjunction w ith established scrapie models. A bovine spongiform encephalopathy (BS E) derived murine model has short incubation periods, high infectivity titre and low amounts of PrP deposited in the brain. A membrane fract ion from scrapie/BSE infected brain is solubilised with Sarkosyl at pH greater than or equal to 9.0. Most PrP is also solubilised. In models of the disease with little deposition of PrP in the brain, this solub ilisation step is particularly effective in reducing the amounts of Pr P sedimented from brain extracts. Gradient centrifugation of the sedim ented fraction shows further separation of infectivity and the residua l PrP. It is concluded that at least some PrPSc in the brain need not be associated directly with infectious agent but is deposited in brain solely as a pathological product of infection. However, a residual se dimentable fraction contains PrP which may be a component of the agent .