IS ABNORMAL PRION PROTEIN THE TRANSMISSIBLE AGENT?
ForAgainst
Amyloid diseasesAmyloid fibrils can induce polymerization of precursorsAmyloid diseases not transmitted by amyloid fibrils
Cell-free conversionPrPres induces conversion of PrPsen Do not know if infectivity is generated
Scrapie strainsPrPres structural variationsToo many strains (20) in mice
PrP null miceNo disease or agent replicationPrP important as agent cofactor or receptor; involved in pathogenesis
GeneticsTSE (both genetic and infectious) PrP mutant causes disease?Retroviruses (both genetic and infectious) PrP mutant = susceptibility gene?
Transgenic miceOverexpression of mutant PrP (Leu102) causes brain diseaseNo PrPres by protein immunoblot Transmission? No disease if no overexpression
IrradiationTarget size too smallTarget size = small virus
CompositionInfectious samples have PrPres May be too little DNA for a virus No virus found so far> 105 PrPres molecules per infectious unit Infectious samples have nucleic acids New viruses can be difficult to find