AMPHOTERICIN-B TREATMENT DISSOCIATES INVIVO REPLICATION OF THE SCRAPIE AGENT FROM PRP ACCUMULATION

SCRAPIE and related animal and human disorders are neurodegenerative diseases 1 characterized by the formation of a modified, partly proteinase-resistant protein (PrP) of the host 2,3, which tends to aggregate as amyloid fibrils 4 and accumulate in the brain of infected individuals 5. There is a general consensus that the pathological form of PrP (PrP(Sc)) is essential for the clinical appearance of the disease 6, but whether it is part of the scrapie agent 7 or a by-product of viral infection 8,9 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 PrP(Sc) 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 PrP(Sc) is necessary for the development of the disease but that it is unlikely to be essential for scrapie replication.