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.
Istituto di Patologia Generale, Università Cattolica S, Cuore, Rome, Italy.
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Ingrosso
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Pocchiari
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