In:
Journal of General Virology, Microbiology Society, Vol. 95, No. 11 ( 2014-11-01), p. 2576-2588
Abstract:
Prion diseases are characterized by the prominent accumulation of the misfolded form of a normal cellular protein (PrP Sc ) in the central nervous system. The pathological features and biochemical properties of PrP Sc in macaque monkeys infected with the bovine spongiform encephalopathy (BSE) prion have been found to be similar to those of human subjects with variant Creutzfeldt–Jakob disease (vCJD). Non-human primate models are thus ideally suited for performing valid diagnostic tests and determining the efficacy of potential therapeutic agents. In the current study, we developed a highly efficient method for in vitro amplification of cynomolgus macaque BSE PrP Sc . This method involves amplifying PrP Sc by protein misfolding cyclic amplification (PMCA) using mouse brain homogenate as a PrP C substrate in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrP Sc contained in the cerebrospinal fluid (CSF) and white blood cells (WBCs), as well as in the peripheral tissues of macaques that have been intracerebrally inoculated with the BSE prion. After clinical signs of the disease appeared in three macaques, we detected PrP Sc in the CSF by serial PMCA, and the CSF levels of PrP Sc tended to increase with disease progression. In addition, PrP Sc was detectable in WBCs at the clinical phases of the disease in two of the three macaques. Thus, our highly sensitive, novel method may be useful for furthering the understanding of the tissue distribution of PrP Sc in non-human primate models of CJD.
Type of Medium:
Online Resource
ISSN:
0022-1317
,
1465-2099
DOI:
10.1099/vir.0.066225-0
Language:
English
Publisher:
Microbiology Society
Publication Date:
2014
detail.hit.zdb_id:
2007065-2
SSG:
12
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