Zoonotic Potential of Chronic Wasting Disease after Adaptation in Intermediate Species.

Chronic wasting disease (CWD) is an emerging disease in Europe. We report an increase in interspecies transmission capacity and zoonotic potential of a moose CWD isolate from Europe after passage in an ovine prion protein-expressing host. Those results indicated some CWD prions could acquire enhanced zoonotic properties following adaptation in an intermediate species.

Classical BSE dismissed as the cause of CWD in Norwegian red deer despite strain similarities between both prion agents.

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain.

Transgenic Mouse Models for the Study of Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are some of the most important health challenges modern medicine and advanced societies face. Indeed, the number of patients affected by one of these illnesses will increase in the following years at the same rate that human life expectancy allows us to live longer. Despite many years of research, NDs remain invariably fatal.

Workplace aggression, wellbeing, and job satisfaction: The specificity in border police organizations.

In male-dominated work contexts, the challenges faced by women and their impact on wellbeing and work attitudes have been documented, most extensively in other than police organizations. This study was conducted as a cross-sectional quantitative descriptive correlational predictive study to validate a model of relationships among workplace aggression, job satisfaction, and wellbeing at work with a sample of 1,066 female and male officers from the Romanian Border Police. The results obtained in the study showed that no differential gender effects were found, although women reported higher levels of workplace aggression than men (1.

Validation of Plasma and CSF Neurofilament Light Chain as an Early Marker for Sporadic Creutzfeldt-Jakob Disease.

Biomarkers are becoming increasingly important for the differential diagnosis of neurodegenerative diseases. Previous observations indicated neurofilament light chain (NfL) as a potential blood-based biomarker for sporadic Creutzfeldt-Jakob disease (sCJD). Here, we investigated the stability, inter-assay/intra-assay variation and the regulation of NfL levels in CSF and plasma in a large cohort of sCJD patients by using a single-molecule array (SIMOA).

Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease.

Background: More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date.

Methods: We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S.

Classical BSE prions emerge from asymptomatic pigs challenged with atypical/Nor98 scrapie.

Pigs are susceptible to infection with the classical bovine spongiform encephalopathy (C-BSE) agent following experimental inoculation, and PrP accumulation was detected in porcine tissues after the inoculation of certain scrapie and chronic wasting disease isolates. However, a robust transmission barrier has been described in this species and, although they were exposed to C-BSE agent in many European countries, no cases of natural transmissible spongiform encephalopathies (TSE) infections have been reported in pigs. Transmission of atypical scrapie to bovinized mice resulted in the emergence of C-BSE prions.

Canine D-PrP polymorphic variant does not provide complete protection against prion infection in small ruminant PrP context.

E/D polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D (equivalent to D position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates.

TREM2 expression in the brain and biological fluids in prion diseases.

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated.

Classical scrapie in small ruminants is caused by at least four different prion strains.

The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrP.

Two distinct conformers of PrP type 1 of sporadic Creutzfeldt-Jakob disease with codon 129VV genotype faithfully propagate in vivo.

Current classifications of sporadic Creutzfeldt-Jakob disease (sCJD) identify five subtypes associated with different disease phenotypes. Most of these histopathological phenotypes (histotypes) co-distribute with distinct pairings of methionine (M)/valine (V) genotypes at codon 129 of the prion protein (PrP) gene and the type (1 or 2) of the disease-associated PrP (PrP). Types 1 and 2 are defined by the molecular mass (~ 21 kDa and ~ 19 kDa, respectively) of the unglycosylated isoform of the proteinase K-resistant PrP (resPrP).

Allelic Interference in Prion Replication Is Modulated by the Convertibility of the Interfering PrP and Other Host-Specific Factors.

Early studies in transgenic mouse lines have shown that the coexpression of endogenous murine prion protein (PrP) and transgenic PrP from another species either inhibits or allows the propagation of prions, depending on the infecting prion strain and interacting protein species. The way whereby this phenomenon, so-called "interference," is modulated remains to be determined. In this study, different transgenic mouse lines were crossbred to produce mice coexpressing bovine and porcine PrP, bovine and murine PrP, or murine and porcine PrP These animals and their respective hemizygous controls were inoculated with several prion strains from different sources (cattle, mice, and pigs) to examine the effects of the simultaneous presence of PrP from two different species.

Met -Glu residues in human PrP β2-α2 loop account for evolutionary resistance to prion infection.

Aims: The amino acid sequence of prion protein (PrP) is a key determinant in the transmissibility of prion diseases. While PrP sequence is highly conserved among mammalian species, minor changes in the PrP amino acid sequence may confer alterations in the transmissibility of prion diseases. Classical bovine spongiform encephalopathy (C-BSE) is the only zoonotic prion strain reported to date causing variant Creutzfeldt-Jacob disease (vCJD) in humans, although experimental transmission points to atypical L-BSE and some classical scrapie isolates as also zoonotic.

Transgenic mouse models for the study of prion diseases.

Prions are unique agents that challenge the molecular biology dogma by transmitting information on the protein level. They cause neurodegenerative diseases that lack of any cure or treatment called transmissible spongiform encephalopathies. The function of the normal form of the prion protein, the exact mechanism of prion propagation between species as well as at the cellular level and neuron degeneration remains elusive.

Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice.

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet, TgMet/Val, and TgVal.

Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation.

Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]-Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species.

The emergence of classical BSE from atypical/Nor98 scrapie.

Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice.

Transgenic mouse models expressing human and macaque prion protein exhibit similar prion susceptibility on a strain-dependent manner.

Cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy (classical-BSE) infectious agent. PrP amino acid sequence is considered to play a key role in the susceptibility to prion strains and only one amino acid change may alter this susceptibility. Macaque and human-PrP sequences have only nine amino acid differences, but the effect of these amino acid changes in the susceptibility to dissimilar prion strains is unknown.

Thermostability as a highly dependent prion strain feature.

Prion diseases are caused by the conversion of physiological PrP into the pathogenic misfolded protein PrP, conferring new properties to PrP that vary upon prion strains. In this work, we analyze the thermostability of three prion strains (BSE, RML and 22L) that were heated at 98 °C for 2 hours. PrP resistance to proteinase K (PrP), residual infectivity by mouse bioassay and in vitro templating activity by protein misfolding cyclic amplification (PMCA) were studied.

Nonpathogenic Heterologous Prions Can Interfere with Prion Infection in a Strain-Dependent Manner.

Co-occurrence of different prion strains into the same host has been recognized as a natural phenomenon for several sporadic Creutzfeldt-Jakob disease (sCJD) patients and natural scrapie cases. The final outcome of prion coinfection is not easily predictable. In addition to the usual factors that influence prion conversion, the replication of one strain may entail positive or negative consequences to the other.

Transmission and Replication of Prions.

Transmissible spongiform encephalopathies (TSEs) are a group of progressive, invariably fatal diseases that affect the nervous system of many mammals including humans. The key molecular event in the pathogenesis of TSEs is the conversion of the cellular prion protein PrP into a disease-associated isoform PrP. The "protein-only hypothesis" argues that PrP itself is the infectious agent.