Predicting the spread-risk potential of chronic wasting disease to sympatric ungulate species

Abstract

Wildlife disease incidence is increasing, resulting in negative impacts on the economy, biodiversity, and potentially human health. Chronic wasting disease (CWD) is a fatal, transmissible spongiform encephalopathy of cervids (wild and captive) which continues to spread geographically resulting in exposure to potential new host species. The disease agent (PrP CWD ) is a misfolded conformer of the cellular prion protein (PrP C ). In Canada, the disease is endemic in Alberta and Saskatchewan, affecting mule and white-tail deer, with lesser impact on elk and moose. As the disease continues to expand, additional wild ungulate species including bison, bighorn sheep, mountain goat, and pronghorn antelope may be exposed. To better understand the speciesbarrier, we reviewed the current literature on taxa naturally or experimentally exposed to CWD to identify susceptible and resistant species. We created a phylogeny of these taxa using cytochrome B and found that CWD susceptibility followed the species phylogeny. Using this phylogeny we estimated the probability of CWD susceptibility for wild ungulate species. We then compared PrP C amino acid polymorphisms among these species to identify which sites segregated between susceptible and resistant species. We identified sites that were significantly associated with susceptibility, but they were not fully discriminating. Finally, we sequenced Prnp from 578 wild ungulates to further evaluate their potential susceptibility. Together, these data suggest the hostrange for CWD will potentially include pronghorn, mountain goat and bighorn sheep, but bison are likely to be more resistant. These findings highlight the need for monitoring potentially susceptible species as CWD continues to expand.

Characterization of the prion protein gene in axis deer (Axis axis) and implications for susceptibility to chronic wasting disease

“…Definitive evidence such as a positive ELISA or IHC test or a protein misfolding cyclic amplification (PMCA) study of axis deer PrP C is needed to conclusively demonstrate axis deer are capable of contracting CWD. However, this research in combination with other work indicating a wider range of susceptible species than previously known [ 13 , 19 ], suggests axis deer in Texas and Hawaii may be susceptible to CWD, and should be managed as an at-risk species for CWD through the implementation of more formalized CWD surveillance. The proactive establishment of a CWD testing programme in axis deer wherever CWD has been detected in other species may be justified.…”

“…The potential for interspecific transmission of CWD between individuals of different cervid species with different PRNP genotypes and PrP C variants is documented in mouse models, and data suggests CWD susceptibility is not limited to species within Cervidae [ 12–15 ]. Phylogenetic analyses and challenge studies indicate species beyond Cervidae, including pronghorn ( Antilocapra americana ), bighorn sheep ( Ovis canadensis ), mountain goat ( Oreamnos americanus ), and squirrel monkeys ( Saimiri sciureus ) may be susceptible to infection by the CWD prion and CWD susceptibility is not monophyletic within Cervidae [ 13 , 16 , 17 ]. The various lines of evidence suggest many, if not all, members of Cervidae are likely susceptible to CWD, including those that naturally occur outside of North America [ 18 , 19 ].…”

Cervid Prion Protein Polymorphisms: Role in Chronic Wasting Disease Pathogenesis

“…In North American moose ( Alces alces spp), polymorphisms at position 36, encoding threonine (T) or N, at position 100 encoding either S or arginine (R), and at position 209 encoding either M or isoleucine (I) have been reported [ 98 , 127 , 129 ]. The PrP sequence of European moose ( A. a. alces ) has high homology to the North American moose with the exception of the variant K to Q at position 109 [ 98 ].…”

Considering the use of the terms strain and adaptation in prion research

“…Other genotypes in white-tailed deer are considered relevant to CWD resistance, including position 116 ( Haley et al., 2019 ). It is important to consider the entire genotype, not simply amino acids 95 or 96, as they are all linked on the PRNP gene ( Cullingham et al., 2020 ).…”