Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation.
Scrapie and related animal and human disorders are neurodegenerative diseases characterized by the formation of a modified, partly proteinase-resistant protein (PrP) of the host, which tends to aggregate as amyloid fibrils and accumulate in the brain of infected individuals. There is a general consensus that the pathological form of PrP (PrPSc) is essential for the clinical appearance of the disease, but whether it is part of the scrapie agent or a by-product of viral infection is still controversial. Here we report that treatment of scrapie-infected hamsters with amphotericin B delays the accumulation in the brain of the proteinase-resistant portion of PrPSc by about 30 days without affecting scrapie replication. The consequence is that hamsters treated with amphotericin B developed clinical signs of disease later than infected controls. We argue that the proteinase-resistant portion of PrPSc is necessary for the development of the disease but that it is unlikely to be essential for scrapie replication.
Xi
Y G
YG
Istituto di Patologia Generale, Università Cattolica S, Cuore, Rome, Italy.
Ingrosso
L
L
Ladogana
A
A
Masullo
C
C
Pocchiari
M
M
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000382:microbiology*; D006224:Cricetinae; D051379:Mice; D018622:PrP 27-30 Protein; D018620:PrPSc Proteins; D011328:Prions / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012608:Scrapie / Q000517:prevention & control*; D014779:Virus Replication / Q000187:drug effects*
D018620:PrPSc Proteins; D011328:Prions; D018622:PrP 27-30 Protein; D000666:Amphotericin B