Search

Chronic wasting disease (CWD) is a relentless epidemic disorder caused by infectious prions that threatens the survival of cervid populations and raises increasing public health concerns in North America. In Europe, CWD was detected for the first time in wild Norwegian reindeer (Rangifer tarandus) and moose (Alces alces) in 2016. In this study, we aimed at comparing the strain properties of CWD prions derived from different cervid species in Norway and North America. Using a classical strain typing approach involving transmission and adaptation to bank voles (Myodes glareolus), we found that prions causing CWD in Norway induced incubation times, neuropathology, regional deposition of misfolded prion protein aggregates in the brain, and size of their proteaseresistant core, different from those that characterize North American CWD. These findings show that CWD prion strains affecting Norwegian cervids are distinct from those found in North America, implying that the highly contagious North American CWD prions are not the proximate cause of the newly discovered Norwegian CWD cases. In addition, Norwegian CWD isolates showed an unexpected strain variability, with reindeer and moose being caused by different CWD strains. Our findings shed light on the origin of emergent European CWD, have significant implications for understanding the nature and the ecology of CWD in Europe, and highlight the need to assess the zoonotic potential of the new CWD strains detected in Europe. [ABSTRACT FROM AUTHOR]

The European Commission asked EFSA for a Scientific Opinion: to revise the state of knowledge about the differences between the chronic wasting disease (CWD) strains found in North America (NA) and Europe and within Europe; to review new scientific evidence on the zoonotic potential of CWD and to provide recommendations to address the potential risks and to identify risk factors for the spread of CWD in the European Union. Full characterisation of European isolates is being pursued, whereas most NA CWD isolates have not been characterised in this way. The differing surveillance programmes in these continents result in biases in the types of cases that can be detected. Preliminary data support the contention that the CWD strains identified in Europe and NA are different and suggest the presence of strain diversity in European cervids. Current data do not allow any conclusion on the implications of strain diversity on transmissibility, pathogenesis or prevalence. Available data do not allow any conclusion on the zoonotic potential of NA or European CWD isolates. The risk of CWD to humans through consumption of meat cannot be directly assessed. At individual level, consumers of meat, meat products and offal derived from CWD‐infected cervids will be exposed to the CWD agent(s). Measures to reduce human dietary exposure could be applied, but exclusion from the food chain of whole carcasses of infected animals would be required to eliminate exposure. Based on NA experiences, all the risk factors identified for the spread of CWD may be associated with animals accumulating infectivity in both the peripheral tissues and the central nervous system. A subset of risk factors is relevant for infected animals without involvement of peripheral tissues. All the risk factors should be taken into account due to the potential co‐localisation of animals presenting with different disease phenotypes. [ABSTRACT FROM AUTHOR]

Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids. Some five decades later, detection of PrPSc in free-ranging Norwegian (NO) reindeer and moose marked the first indication of CWD in Europe. To assess the properties of these emergent NO prions and compare them with NA CWD we used transgenic (Tg) and gene targeted (Gt) mice expressing PrP with glutamine (Q) or glutamate (E) at residue 226, a variation in wild type cervid PrP which influences prion strain selection in NA deer and elk. Transmissions of NO moose and reindeer prions to Tg and Gt mice recapitulated the characteristic features of CWD in natural hosts, revealing novel prion strains with disease kinetics, neuropathological profiles, and capacities to infect lymphoid tissues and cultured cells that were distinct from those causing NA CWD. In support of strain variation, PrPSc conformers comprising emergent NO moose and reindeer CWD were subject to selective effects imposed by variation at residue 226 that were different from those controlling established NA CWD. Transmission of particular NO moose CWD prions in mice expressing E at 226 resulted in selection of a kinetically optimized conformer, subsequent transmission of which revealed properties consistent with NA CWD. These findings illustrate the potential for adaptive selection of strain conformers with improved fitness during propagation of unstable NO prions. Their potential for contagious transmission has implications for risk analyses and management of emergent European CWD. Finally, we found that Gt mice expressing physiologically controlled PrP levels recapitulated the lymphotropic properties of naturally occurring CWD strains resulting in improved susceptibilities to emergent NO reindeer prions compared with over-expressing Tg counterparts. These findings underscore the refined advantages of Gt models for exploring the mechanisms and impacts of strain selection in peripheral compartments during natural prion transmission., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CS is a Founder, Chief Scientific Officer and Member of the Board of Directors of Amprion Inc, a biotechnology company that focuses on the commercial use of PMCA and RT-QuIC for high-sensitivity detection of misfolded protein aggregates including prion diseases. The University of Texas Health Science Center at Houston has licensed patents and patent applications to Amprion. The remaining authors declare that they have no conflicts of interest with the contents of this article.