A novel approach in the molecular differentiation of prion strains
The origin of the transmissible agent involved in the foodborne epidemic of bovine spongiform encephalopathy (BSE) remains a mystery. It has recently been proposed that this could have been the result of the recycling of an atypical, more probably sporadic, form of BSE (called bovine amyloidotic spongiform encephalopathy, or L-type BSE) in an intermediate host, such as sheep. A team from the French Food Safety Agency has identified a prion protein characteristic that is unique to some natural but unusual sheep scrapie cases. This finding may provide a novel method by which to study prion diversity and their possible changes during cross-species transmission. Mystery still surrounds the origin of the transmissible agent involved in the food-borne epidemic of bovine spongiform encephalopathy (BSE). Classical BSE, more commonly known as mad cow disease, is a known cause of a variant form of the incurable, degenerative neurological disorder Creutzfeldt-Jakob disease in humans. It has recently been proposed that this could have been the result of the recycling of an atypical, more probably sporadic form of BSE (called bovine amyloidotic spongiform encephalopathy, or L-type BSE) in an intermediate host, such as sheep. The team analyzed the molecular features of the disease-associated protease-resistant prion protein (PrPres) to determine any differences which might discriminate between scrapie and BSE cases. The researchers sampled PrPres from the brains of transgenic mice overexpressing the ovine prion protein after experimental infection with prions from bovine classical BSE, L-type BSE, and ovine scrapie. Scrapie cases were found to include rare “CH1641-Like” isolates, which share some PrPres molecular features with classical BSE and L-type BSE. The molecular features of the prion protein in the “CH1641-like” sheep scrapie cases more closely resemble those found in L-type BSE compared to classical BSE. However, from a series of four “CH1641-like” scrapie cases, the researchers found a pathological C-terminal prion protein product that was undetectable from both L-type and classical BSE transmitted to such mice, clearly suggesting that such scrapie isolates are not linked to these BSE forms. Further studies to confirm this discriminating factor are needed in sheep, especially from sheep experimentally infected with L-type BSE, which were not available for this study. These findings add a novel approach for the discrimination of prions that may help to understand their possible changes during cross-species transmissions.
A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine “CH1641-Like” Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice. 2008 PLoS Pathog 4(8): e1000137
The protease-resistant prion protein (PrPres) of a few natural scrapie isolates identified in sheep, reminiscent of the experimental isolate CH1641 derived from a British natural scrapie case, showed partial molecular similarities to ovine bovine spongiform encephalopathy (BSE). Recent discovery of an atypical form of BSE in cattle, L-type BSE or BASE, suggests that also this form of BSE might have been transmitted to sheep. We studied by Western blot the molecular features of PrPres in four “CH1641-like” natural scrapie isolates after transmission in an ovine transgenic model (TgOvPrP4), to see if “CH1641-like” isolates might be linked to L-type BSE. We found less diglycosylated PrPres than in classical BSE, but similar glycoform proportions and apparent molecular masses of the usual PrPres form (PrPres #1) to L-type BSE. However, the “CH1641-like” isolates differed from both L-type and classical BSE by an abundant, C-terminally cleaved PrPres product (PrPres #2) specifically recognised by a C-terminal antibody (SAF84). Differential immunoprecipitation of PrPres #1 and PrPres #2 resulted in enrichment in PrPres #2, and demonstrated the presence of mono- and diglycosylated PrPres products. PrPres #2 could not be obtained from several experimental scrapie sources (SSBP1, 79A, Chandler, C506M3) in TgOvPrP4 mice, but was identified in the 87V scrapie strain and, in lower and variable proportions, in 5 of 5 natural scrapie isolates with different molecular features to CH1641. PrPres #2 identification provides an additional method for the molecular discrimination of prion strains, and demonstrates differences between “CH1641-like” ovine scrapie and bovine L-type BSE transmitted in an ovine transgenic mouse model.
Related:
- New forms of bovine spongiform encephalopathy
- Four separate types of Creutzfeldt-Jakob disease?
- Genes contributing to prion pathogenesis
- What the heck are prions for?
Tags: Agriculture, Biology, Emerging disease, Food, Microbiology, Prions, Science
