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Prion diseases are transmissible, fatal neurologic diseases that include Creutzfeldt-Jakob Disease (CJD) in humans, chronic wasting disease (CWD) in cervids, bovine spongiform encephalopathy (BSE) in cattle and scrapie in sheep. Prions are extremely difficult to inactivate and established methods to reduce prion infectivity are often dangerous, caustic, expensive, or impractical. Identifying viable and safe methods for treating prion contaminated materials is important for hospitals, research facilities, biologists, hunters, and meat-processors. For three decades, some prion researchers have used a phenolic product called Environ LpH (eLpH) to inactivate prions. ELpH has been discontinued, but a similar product, Wex-cide 128, containing the similar phenolic chemicals as eLpH is now available. In the current study, we directly compared the anti-prion efficacy of eLpH and Wex-cide 128 against prions from four different species (hamster 263K, cervid CWD, mouse 22L and human CJD). Decontamination was performed on either prion infected brain homogenates or prion contaminated steel wires and mouse bioassay was used to quantify the remaining prion infectivity. Our data show that both eLpH and Wex-cide 128 removed 4.0–5.5 logs of prion infectivity from 22L, CWD and 263K prion homogenates, but only about 1.25–1.50 logs of prion infectivity from human sporadic CJD. Wex-cide 128 is a viable substitute for inactivation of most prions from most species, but the resistance of CJD to phenolic inactivation is a concern and emphasizes the fact that inactivation methods should be confirmed for each target prion strain. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrPSc). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrPC) into infectious PrPSc. By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrPSc. In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrPC allotype to PrPSc in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrPSc with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrPC containing an M or V at residue 129 having a similar propensity to misfold into PrPSc thus causing sCJD. By contrast, PrPSc with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrPSc containing V at residue 129. In both types of CJD, the PrPSc allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrPSc allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD. [ABSTRACT FROM AUTHOR]

In most forms of prion disease, infectivity is present primarily in the central nervous system or immune system organs such as spleen and lymph node. However, a transgenic mouse model of prion disease has demonstrated that prion infectivity can also be present as amyloid deposits in heart tissue. Deposition of infectious prions as amyloid in human heart tissue would be a significant public health concern. Although abnormal disease-associated prion protein (PrPSc) has not been detected in heart tissue from several amyloid heart disease patients, it has been observed in the heart tissue of a patient with sporadic Creutzfeldt-Jakob Disease (sCJD), the most common form of human prion disease. In order to determine whether prion infectivity can be found in heart tissue, we have inoculated formaldehyde fixed brain and heart tissue from two sCJD patients, as well as prion protein positive fixed heart tissue from two amyloid heart disease patients, into transgenic mice overexpressing the human prion protein. Although the sCJD brain samples led to clinical or subclinical prion infection and deposition of PrPSc in the brain, none of the inoculated heart samples resulted in disease or the accumulation of PrPSc. Thus, our results suggest that prion infectivity is not likely present in cardiac tissue from sCJD or amyloid heart disease patients. [ABSTRACT FROM AUTHOR]

A correction to the article "The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients," in the 2016 issue is presented.

Presents a commentary on the identification of possible animal origins on prion disease in human beings. Definition of transmissible neurodegenerative disease of mammals which include sporadic and variant Creutzfeldt-Jakob disease in humans; Findings of a study reported in this issue which challenges the conclusion that there is only one strain of bovine spongiform encephalopathy (BSE); Details on the study and how it was conducted; Why the diseases are difficult to identify as a source of infection to humans; Call for more BSE testing to look for new strains which could cause a danger to humans.

The causative agent of the transmissible spongiform encephalopathies (TSE) or prion diseases, which include sheep scrapie, mad cow disease, and human variant Creutzfeldt-Jakob disease (vCJD), is debated. the TSE agent is an infectious, self-replicating prion protein called PrP[supSc]. This abnormal protein is considered to be an insoluble, partially protease-resistant isoform of a normal cellular protein, PrP[supC], which is both soluble and protease-sensitive. Studies in sheep infected with scrapie or bovine spongiform encephalopathy illustrated not only that different sheep scrapie strains could target different cells in the brain, but also that the deposition and size of PrP supSc in bovine spongiform encephalopathy-versus scrapie-infected sheep were different. Convincing evidence was presented that TSE infection via the tongue is more efficient than oral infection, suggesting that the tongue may be a route of TSE agent entry following natural oral exposure. In terms of TSE diagnostics, a promising assay may finally provide the TSE field with a quantitative and sensitive in vitro method for measuring mouse scrapie infectivity.

Abstract: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that include Creutzfeldt–Jakob disease, bovine spongiform encephalopathy and sheep scrapie. Although one of the earliest events during TSE infection is the cellular uptake of protease resistant prion protein (PrP-res), this process is poorly understood due to the difficulty of clearly distinguishing input PrP-res from either PrP-res or protease-sensitive PrP (PrP-sen) made by the cell. Using PrP-res tagged with a unique antibody epitope, we examined PrP-res uptake in neuronal and fibroblast cells exposed to three different mouse scrapie strains. PrP-res uptake was rapid and independent of scrapie strain, cell type, or cellular PrP expression, but occurred in only a subset of cells and was influenced by PrP-res preparation and aggregate size. Our results suggest that PrP-res aggregate size, the PrP-res microenvironment, and/or host cell-specific factors can all influence whether or not a cell takes up PrP-res following exposure to TSE infectivity. [Copyright &y& Elsevier]