Review on PRNP genetics and susceptibility to chronic wasting disease of Cervidae

Abstract

To date, chronic wasting disease (CWD) is the most infectious form of prion disease affecting several captive, free ranging and wild cervid species. Responsible for marked population declines in North America, its geographical spread is now becoming a major concern in Europe. Polymorphisms in the prion protein gene (PRNP) are an important factor influencing the susceptibility to prions and their rate of propagation. All reported cervid PRNP genotypes are affected by CWD. However, in each species, some polymorphisms are associated with lower attack rates and slower progression of the disease. This has potential consequences in terms of genetic selection, CWD diffusion and strain evolution. CWD also presents a zoonotic risk due to prions capacity to cross species barriers. This review summarizes our current understanding of CWD control, focusing on PRNP genetic, strain diversity and capacity to infect other animal species, including humans.

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 ].…”

Novel Single Nucleotide Polymorphisms (SNPs) and Genetic Features of the Prion Protein Gene (PRNP) in Quail (Coturnix japonica)

“…In addition, the 23 and 12 bp insertion/deletion polymorphisms located in the promoter region were associated with the expression of the bovine PRNP gene and were reported to affect vulnerability to BSE ( 12 ). Furthermore, genetic polymorphisms at codons 95, 96, and 132 of the cervid PRNP gene played an important role in susceptibility to CWD in the cervidae family ( 13 – 15 ). Recent studies have reported that prion disease-resistant specific amino acids of PrPs, including S167 in horses and D159 in dogs, conferred resistance to conversion from PrP C to PrP Sc ( 16 , 17 ).…”

Estimating sequence diversity of prion protein gene (PRNP) in Portuguese populations of two cervid species: red deer and fallow deer

“…The analysis of the PRNP diversity in European cervid species is still limited but some studies carried out in Britain, Norway and Sweden, showed that some PRNP genetic variations can be related with CWD susceptibility/resistance [18]. The variations S225Y and P242L found in caribou/reindeer were associated to a higher risk of infection and the N138 polymorphism in fallow deer has been associated with natural resistance [12].…”