Prions cause fatal and transmissible neurodegenerative diseases, including Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE). After the BSE epidemic, and the associated human infections, began in 1996 in the United Kingdom, general concerns have been raised about animal prions. We detected a prion disease in dromedary camels (Camelus dromedarius) in Algeria. Symptoms suggesting prion disease occurred in 3.1% of dromedaries brought for slaughter to Ouargla abattoir in 2015–2016. We confirmed diagnosis by detecting pathognomonic neurodegeneration and disease-specific prion protein (PrPSc) in brain tissues from 3 symptomatic animals. Prion detection in lymphoid tissues is suggestive of the infectious nature of the disease. PrPSc biochemical characterization showed differences with BSE and scrapie. Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.

Chronic wasting disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a large scale surveillance program. The cases occurred in 13–14-year-old female moose, and we detected an abnormal form of prion protein (PrPSc) in the brain but not in lymphoid tissues. Immunohistochemistry revealed that the moose shared the same neuropathologic phenotype, characterized by mostly intraneuronal deposition of PrPSc. This pattern differed from that observed in reindeer and has not been previously reported in CWD-infected cervids. Moreover, Western blot revealed a PrPSc type distinguishable from previous CWD cases and from known ruminant prion diseases in Europe, with the possible exception of sheep CH1641. These findings suggest that these cases in moose represent a novel type of CWD.

In order to assess the susceptibility of bank voles to chronic wasting disease (CWD), we inoculated voles carrying isoleucine or methionine at codon 109 (Bv109I and Bv109M, respectively) with CWD isolates from elk, mule deer and white-tailed deer. Efficient transmission rate (100%) was observed with mean survival times ranging from 156 to 281 days post inoculation. Subsequent passages in Bv109I allowed us to isolate from all CWD sources the same vole-adapted CWD strain (Bv^109ICWD), typified by unprecedented short incubation times of 25–28 days and survival times of ∼35 days. Neuropathological and molecular characterisation of Bv^109ICWD showed that the classical features of mammalian prion diseases were all recapitulated in less than one month after intracerebral inoculation. Bv^109ICWD was characterised by a mild and discrete distribution of spongiosis and relatively low levels of protease-resistant PrP^Sc (PrP^res) in the same brain regions. Despite the low PrP^res levels and the short time lapse available for its accumulation, end-point titration revealed that brains from terminally-ill voles contained up to 10^8,4 i.c. ID₅₀ infectious units per gram. Bv^109ICWD was efficiently replicated by protein misfolding cyclic amplification (PMCA) and the infectivity faithfully generated in vitro, as demonstrated by the preservation of the peculiar Bv^109ICWD strain features on re-isolation in Bv109I. Overall, we provide evidence that the same CWD strain was isolated in Bv109I from the three-cervid species. Bv^109ICWD showed unique characteristics of “virulence”, low PrP^res accumulation and high infectivity, thus providing exceptional opportunities to improve basic knowledge of the relationship between PrP^Sc, neurodegeneration and infectivity. Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids and is expanding increasingly in the USA and Canada. Animal models are of key importance in the study of prion diseases but their development for CWD has long been hampered by its very inefficient transmission to wild-type mice. Significant progress was made following the generation of transgenic mice over-expressing cervid PrP. Here we show that the bank vole (Myodes glareolus), a wild rodent species that we demonstrated to be susceptible to many animal and human prion diseases, is also very susceptible to CWD from elk, mule deer and white-tailed deer. Adaptation of CWD to bank vole led to the isolation of a prion strain with peculiar characteristics: unprecedented short incubation and survival times, respectively of 25–28 and ∼35 days, low PrP^Sc levels compared with other vole-adapted prion strains and high infectious titre. These features were all faithfully maintained upon the generation of this strain in vitro by protein misfolding cyclic amplification. The development of a model for prion diseases that led to disease in less than one month accumulating high infectious titres but low PrP^Sc levels, represents a significant tool for investigating the still unclear relationship between PrP^Sc, neurodegeneration and infectivity in prion diseases.

Prion diseases are fatal neurodegenerative disorders with known natural occurrence in humans and a few other mammalian species. The diseases are experimentally transmissible, and the agent is derived from the host-encoded cellular prion protein (PrP^C), which is misfolded into a pathogenic conformer, designated PrP^Sc (scrapie). Aggregates of PrP^Sc molecules, constitute proteinaceous infectious particles, known as prions. Classical scrapie in sheep and goats and chronic wasting disease (CWD) in cervids are known to be infectious under natural conditions. In CWD, infected animals can shed prions via bodily excretions, allowing direct host-to-host transmission or indirectly via prion-contaminated environments. The robustness of prions means that transmission via the latter route can be highly successful and has meant that limiting the spread of CWD has proven difficult. In 2016, CWD was diagnosed for the first time in Europe, in reindeer (Rangifer tarandus) and European moose (Alces alces). Both were diagnosed in Norway, and, subsequently, more cases were detected in a semi-isolated wild reindeer population in the Nordfjella area, in which the first case was identified. This population was culled, and all reindeer (approximately 2400) were tested for CWD; 18 positive animals, in addition to the first diagnosed case, were found. After two years and around 25,900 negative tests from reindeer (about 6500 from wild and 19,400 from semi-domesticated) in Norway, a new case was diagnosed in a wild reindeer buck on Hardangervidda, south of the Nordfjella area, in 2020. Further cases of CWD were also identified in moose, with a total of eight in Norway, four in Sweden, and two cases in Finland. The mean age of these cases is 14.7 years, and the pathological features are different from North American CWD and from the Norwegian reindeer cases, resembling atypical prion diseases such as Nor98/atypical scrapie and H- and L-forms of BSE. In this review, these moose cases are referred to as atypical CWD. In addition, two cases were diagnosed in red deer (Cervus elaphus) in Norway. The emergence of CWD in Europe is a threat to European cervid populations, and, potentially, a food-safety challenge, calling for a swift, evidence-based response. Here, we review data on surveillance, epidemiology, and disease characteristics, including prion strain features of the newly identified European CWD agents.

Gerstmann-Sträussler-Scheinker disease (GSS) is an inherited neurodegenerative disorder associated with mutations in the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrP^res) of 6–8 kDa. With the exception of a few GSS cases characterized by co-accumulation of PrP^res of 21 kDa, efforts to transmit GSS to rodents have been unsuccessful. As a result, GSS subtypes exclusively associated with 6–8 kDa PrP^res have often been considered as non-transmissible proteinopathies rather than true prion diseases. We show that GSS with P102L, A117V and F198S mutations transmit efficiently and produce distinct pathological phenotypes in bank voles (M. glareolus), irrespective of the presence of 21 kDa PrP^res in the inoculum, demonstrating that GSS is a genuine prion disease characterized by both transmissibility and strain variation.

Prion diseases are caused by a misfolding of the cellular prion protein (PrP) to a pathogenic isoform named PrP^Sc. Prions exist as strains, which are characterized by specific pathological and biochemical properties likely encoded in the three-dimensional structure of PrP^Sc. However, whether cofactors determine these different PrP^Sc conformations and how this relates to their specific biological properties is largely unknown. To understand how different cofactors modulate prion strain generation and selection, Protein Misfolding Cyclic Amplification was used to create a diversity of infectious recombinant prion strains by propagation in the presence of brain homogenate. Brain homogenate is known to contain these mentioned cofactors, whose identity is only partially known, and which facilitate conversion of PrP^C to PrP^Sc. We thus obtained a mix of distinguishable infectious prion strains. Subsequently, we replaced brain homogenate, by different polyanionic cofactors that were able to drive the evolution of mixed prion populations toward specific strains. Thus, our results show that a variety of infectious recombinant prions can be generated in vitro and that their specific type of conformation, i.e., the strain, is dependent on the cofactors available during the propagation process. These observations have significant implications for understanding the pathogenesis of prion diseases and their ability to replicate in different tissues and hosts. Importantly, these considerations might apply to other neurodegenerative diseases for which different conformations of misfolded proteins have been described.