association between PrP and infectivity in scrapie and BSE infected mouse brain

• Published in: Archives of virology 1996-01, Vol.141 (2), p.275-289
• Main Authors: Somerville, R.A, Dunn, A.J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; bovine spongiform encephalopathy; brain; Brain - pathology; Brain - virology; Cattle; Cell Fractionation; Cell Membrane - virology; cell membranes; Centrifugation, Density Gradient; density gradient centrifugation; Detergents; Electrophoresis, Polyacrylamide Gel; Encephalopathy, Bovine Spongiform - physiopathology; Experimental viral diseases and models; glycoproteins; Infectious diseases; Medical sciences; Mice; Mice, Inbred Strains; Molecular Weight; pathogenicity; prion-related protein; Prions - isolation & purification; Prions - pathogenicity; PrPSc proteins; purification; Reference Values; Sarcosine - analogs & derivatives; Scrapie - physiopathology; Viral diseases; Virulence
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/bf01718399

The structure of the scrapie agent remains unknown. However scrapie infectivity tends to co-sediment with an infection specific fraction of the glycoprotein PrP (PrPSc) under conditions which solubilise the normal form of this protein (PrPc); accordingly, PrP has been proposed as a candidate component of the agent. To investigate this further we have been examining a new scrapie-related murine model in conjunction with established scrapie models. A bovine spongiform encephalopathy (BSE) derived murine model has short incubation periods, high infectivity titre and low amounts of PrP deposited in the brain. A membrane fraction 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 solubilisation step is particularly effective in reducing the amounts of PrP sedimented from brain extracts. Gradient centrifugation of the sedimented fraction shows further separation of infectivity and the residual 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 sedimentable fraction contains PrP which may be a component of the agent.