Chronic Wasting Disease (CWD) in Cervids and the Consequences of a Mutable Protein Conformation

Abstract

Chronic wasting disease (CWD) is a prion disease of cervids (deer, elk, moose, etc.). It spreads readily from CWDcontaminated environments and among wild cervids. As of 2022, North American CWD has been found in 29 states, four Canadian provinces and South Korea. The Scandinavian form of CWD originated independently. Prions propagate their pathology by inducing a natively expressed prion protein (PrP C ) to adopt the prion conformation (PrP Sc ). PrP C and PrP Sc differ solely in their conformation. Like other prion diseases, transmissible CWD prions can arise spontaneously. The CWD prions can respond to selection pressures resulting in the emergence of new strain phenotypes. Annually, 11.5 million Americans hunt and harvest nearly 6 million deer, indicating that CWD is a potential threat to an important American food source. No tested CWD strain has been shown to be zoonotic. However, this may not be true for emerging strains. Should a zoonotic CWD strain emerge, it could adversely impact the hunting economy and game meat consumers.

Transmission, Strain Diversity, and Zoonotic Potential of Chronic Wasting Disease

“…As described above, several reports have confirmed that some Prnp polymorphisms confer relative resistance to CWD infection [18,[70][71][72][73][74][75][76][77]. Thus, one strategy to minimize CWD spreading might be to perform selective breeding to produce animals with several polymorphic variants known to decrease infection.…”

“…In addition, prion protein polymorphisms (Table 1), as well as small differences on the aminoacid sequence between different cervid species, may lead to the emergence of new prion strains when animals are infected with PrP Sc carrying a mismatch sequence from host PrP C [66][67][68][69]. It is well-established that the presence of certain polymorphic variants in cervids (Table 1) may confer resistance to CWD infection [18,70,71]. For example, infection of whitetailed deer harboring rarer polymorphisms at position 95 and 96 of PrP C led to a prolonged incubation period compared to animals with more prevalent polymorphisms [72,73].…”

“…It is well-established that the presence of certain polymorphic variants in cervids ( Table 1 ) may confer resistance to CWD infection [ 18 , 70 , 71 ]. For example, infection of white-tailed deer harboring rarer polymorphisms at position 95 and 96 of PrP C led to a prolonged incubation period compared to animals with more prevalent polymorphisms [ 72 , 73 ].…”

“…Another alternative is a spontaneous switch on PrP C conformation (Figure 1), perhaps triggered by changes on the cellular milieu or a defect on the cellular response to protein misfolding [7]. In the past several decades, the disease has been rapidly and progressively spreading geographically and now affects 30 states in the USA, four Canadian provinces, South Korea, and has been recently reported in various countries of Northern Europe, including Norway, Sweden, and Finland [16][17][18][19]. By far the country most affected by CWD is the USA.…”

“…In the past several decades, the disease has been rapidly and progressively spreading geographically and now affects 30 states in the USA, four Canadian provinces, South Korea, and has been recently reported in various countries of Northern Europe, including Norway, Sweden, and Finland [ 16 , 17 , 18 , 19 ]. By far the country most affected by CWD is the USA.…”