Chronic wasting disease prions from Norwegian cervids: Assessing the pathogenesis, shedding, spillover and zoonotic potential

The continued spread of Chronic Wasting Disease (CWD) continues to threaten deer populations in North America, and its uncertain zoonotic potential is a public health concern. Since the first case of CWD in Norwegian reindeer and moose in 2016, the disease is found in several Norwegian regions and Nordic countries. The Veterinary Institute’s collaboration with key partners has identified several CWD strains in Norwegian reindeer, moose and deer. Of particular importance, these prion strains are unrelated to those currently present in North America. These Nordic findings have clear implications for the future management of these emerging European prions. The project consortium has strong complementary skills and expertise. This ambitious project will combine animal experiments in reindeer and mice models with in vitro experiments using the most recent and sensitive technologies (RT-QuIC, PMCA) and a potential field -deployable test, the Minnesota-QuiC test (MN-QuiC). The main objective of work package 1 is to study when and where prions can be detected in the body and excreta of reindeer after experimental oral exposure to CWD prions. Much of the resources were dedicated this initial year, specifically forP1 -NVI and P10-CFIA), to ensure the best recruitment process of the reindeer for the experiment as well as ensuring the safe and efficient transport of these animals from Norway to the facilities in Canada. The reindeer have now arrived at the Canadian facilities, where they will undergo an acclimatization period prior to the start of the experimental inoculation procedures. In work package 2, the examination of various tissues from CWD cervids has been initiated using both traditional methods and the ultrasensitive amplification method PMCA. Preliminary findings are anticipated to be suitable for publication in the near future (P1, P4, and P5). Furthermore, collaborative efforts between P1 and the producers of the test P9 have focused on evaluating the MN-QuIC method on Norwegian CWD isolates. Initial results indicate promising efficacy in detecting prions in the lymph nodes of reindeer; however, further optimization is required for its application in analyzing brain tissues across all cervid species. With respect to Work Packages 3 and 4, transmission studies in rodent models have already commenced as part of the ERA-NET ICRAD project (NFR number: 322907, involving P2, P5, P6, and P7), and additional investigations are currently in progress.

The inexorable contagious transmission of chronic wasting disease (CWD) prions continues to threaten the survival of cervid populations in North America, and their uncertain zoonotic potential raises concerns for public health. Since the first case of CWD in Norwegian reindeer and moose in 2016, the disease is found in several Norwegian regions and Nordic countries. Our recent collaborations with key partners in this proposal have identified multiple CWD strains in Norwegian reindeer, moose and red deer. Of particular importance, these strains are unrelated to those currently sustaining the North American epidemic. These findings have clear implications for the future management of these emerging European prions. With the strong and complementary skills and expertise of the consortium and the unprecedented resources it represents, this ambitious project will combine live animal experiments in reindeer and mice models, in addition to in vitro experiments with the most recent and sensitive technologies (RT-QuIC, PMCA) and a potential field-deployable test, the Minnesota-QuiC test (MN-QuiC). The potential of CWD strains for spreading among cervids and for infecting new animal species, including humans, essentially depends on two main factors: the level of EXPOSURE to CWD infectivity and the intrinsic SUSCEPTIBILITY of the EXPOSED SPECIES to the different CWD strains. EmergingCWD aims at addressing both sides of this issue. It will provide a new understanding of how the emerging CWD prions identified in Norway can spread both within and between host species. Being different from most known infectious agents like viruses and bacteria, knowledge about prions, their infectiousness, and their transmission mechanisms continues to lag behind. Given the possible dramatic consequences of prion-related disease, this project will represent a decisive input to close this knowledge gap of relevance to both Norway and the international scientific community.