Ultrasensitive detection of PrPSc in the cerebrospinal fluid and blood of macaques infected with bovine spongiform encephalopathy prion
| Autor: | Yuichi Murayama, Keiji Terao, Yoshio Yamakawa, Morikazu Imamura, Minoru Tobiume, Noriko Shimozaki, Hiroaki Shibata, Tetsutaro Sata, Kentaro Masujin, Fumiko Ono, Tomoaki Yamamura |
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| Rok vydání: | 2014 |
| Předmět: |
Male
PrPSc Proteins animal diseases Bovine spongiform encephalopathy Central nervous system Biology Macaque Creutzfeldt-Jakob Syndrome Cellular protein Mice Cerebrospinal fluid Virology biology.animal medicine Animals Humans Tissue Distribution Disease progression medicine.disease In vitro nervous system diseases Encephalopathy Bovine Spongiform Disease Models Animal Macaca fascicularis medicine.anatomical_structure Protein Misfolding Cyclic Amplification Cattle |
| Zdroj: | Journal of General Virology. 95:2576-2588 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/vir.0.066225-0 |
| Popis: | Prion diseases are characterized by the prominent accumulation of the misfolded form of a normal cellular protein (PrPSc) in the central nervous system. The pathological features and biochemical properties of PrPScin 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 forin vitroamplification of cynomolgus macaque BSE PrPSc. This method involves amplifying PrPScby protein misfolding cyclic amplification (PMCA) using mouse brain homogenate as a PrPCsubstrate in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrPSccontained 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 PrPScin the CSF by serial PMCA, and the CSF levels of PrPSctended to increase with disease progression. In addition, PrPScwas 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 PrPScin non-human primate models of CJD. |
| Databáze: | OpenAIRE |
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