NR ALAK
AU Somerville,R.A.; Dunn,A.J.
TI The association between PrP and infectivity in scrapie and BSE infected mouse brain
QU Archives of Virology 1996; 141(2): 275-89
PT journal article
AB 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 > or = 9.0. Most PrP is also solubilised. In models of the disease with little deposition of the 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 agents 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.
IN Ein auf eine BSE-Infektion zurückgehendes Mausmodel zur Untersuchung der Prionkrankheiten zeichnet sich durch kurze Inkubatipnszeiten, hohe Infektivitätstiter und ein geringes Maß an Prionproteinablagerungen aus. Eine Membranfraktion infizierter Gehirne wurde mit Sarkosyl bei pH-Werten von mindestens 9,0 gelöst. Dabei ging auch der größte Teil der Prionproteine in Lösung. Durch Gradientenzentrifugation soll eine weitere Trennung des verbliebenen Restes von Prionprotein von der Infektiosität gelungen sein. Die Autoren schließen daraus, dass die Prione pathologische Abfallprodukte der Infektion seien und das zumindest ein Teil der proteaseresistenten Prionproteine nicht direkt mit der Infektiosität in Verbindung steht.
ZR 63
MH Animal; Brain/pathology/*virology; Cattle; Cell Fractionation; Cell Membrane/virology; Centrifugation, Density Gradient; Detergents; Electrophoresis, Polyacrylamide Gel; Encephalopathy, Bovine Spongiform/*physiopathology; Mice; Mice, Inbred Strains; Molecular Weight; Prions/isolation & purification/*pathogenicity; Reference Values; Sarcosine/analogs & derivatives; Scrapie/*physiopathology; Virulence
AD BBSRC & MRC Neuropathogenesis Unit, Institute for Animal Health, Edinburgh, U.K.
SP englisch
PO Österreich