Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease

Abstract

The prion protein (PrP) gene was characterized in 1482 free-ranging mule deer (Odocoileus hemionus) from Wyoming and Colorado. Using DNA sequences from 363 deer, dimorphisms at codons 20 (aspartate/glycine) and 225 [serine (S)/phenylalanine (F)] were found; silent changes occurred at codons 131 (tyrosine) and 247 (isoleucine). The remaining samples were surveyed for codon 225 genotype and all were characterized for chronic wasting disease (CWD) infection status. A total of 112 deer with the genotype 225SF or FF were found, of which one was CWD-positive; 1370 were 225SS, with 289 positive for CWD. Among CWD-negative deer, the frequency of 225SF/FF genotypes was 9?3 % but among CWD-positive deer it was only 0?3 %. For all samples combined, CWD status was not independent of codon 225 genotype (P<0?0001). The odds that a deer of the 225SS genotype was CWD-infected were 30 times greater (95 % confidence intervals=4-213) than for a 225SF deer. The proportion of 225SF animals in sampled subpopulations varied from 0 to 18 %; the CWD prevalence varied from 0 to 25 %. However, no relationship was observed between genotype frequency and CWD prevalence in different areas. The PrP sequences of experimentally infected mule deer were analysed from pre-existing projects and 10 animals were found with 225SF genotypes, all of which were positive for CWD. Data available from some of these animals suggest that the 225SF genotype could be associated with longer incubation periods in CWD infection compared with the 225SS genotype. INTRODUCTIONChronic wasting disease (CWD) is an infectious and fatal neurodegenerative disease of cervid species in North America (Williams & Young, 1980, 1982. One of the transmissible spongiform encephalopathies (TSEs) (Prusiner, 2004), also known as prion diseases, CWD occurs endemically and epidemically (Miller et al., 2000; in wild mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk or wapiti (Cervus elaphus nelsoni) in several states of the USA as well as in captive or farmed cervids outside these areas (Williams, 2002;.Although CWD is not perceived as an immediate major threat to deer or elk populations, it is of concern and interest for several reasons: (i) the possibility that wild herds could be gradually destroyed by CWD (Gross & Miller, 2001) due to the persistence of the infectious agent in the environment (Miller et al., 1998 and the lethality of the disease; (ii) the unknown nature of circumstances, if any, under which this disease could affect a human; (iii) the greater understanding of human TSEs that could accrue by knowing more about related mammalian prion diseases that have not been well understood before; (iv) the economic impact of CWD on game farming; and (v) the possible spread of CWD to other members of the cervid family worldwide through unregulated commerce and transport of captive animals (Williams & Miller, 2003).In other acquired prion diseases, notably scrapie of sheep and variant Creutzfeldt-Jakob disease (vCJD) in humans, amino...

A prion disease of cervids: Chronic wasting disease

“…However species specific polymorphisms exist, and accumulating evidence suggests that species-specific polymorphisms affect susceptibility to CWD infection with the presently existing strains. In naturally infected mule deer, serine homozygosity at Prnp codon 225 seems to increase risk for CWD infection, as the probability that a CWD-infected animal was 225SS was 30 times greater than for S/F or FF when the frequency of genotypes was compared among CWD negative and positive deer (n = 1482 deer) [34]. As noted above, 225SF mule deer had a delay in the kinetics of experimental infection [17].…”

“…Prnp is highly conserved, and few amino acid residues differ among cervids [1,34,58]. However species specific polymorphisms exist, and accumulating evidence suggests that species-specific polymorphisms affect susceptibility to CWD infection with the presently existing strains.…”

“…However, Safar et al have reported differing conformational characteristics for PrP Sc from CWD-infected white-tailed deer and elk directly, using a conformation dependent immunoassay (CDI) [71], which supports the existence of CWD strains. The possible existence of CWD strains is perhaps not entirely surprising, considering that there are genetic Prnp differences among deer and elk that could influence PrP Sc conformation [34,36,58].…”

PrPgenetics in ruminant transmissible spongiform encephalopathies

“…From almost 1 800 alleles that have been published for mule deer and white-tailed deer at least 25% had an additional mutation. Of the 562 wapiti PrP sequences 18% carried the only known polymorphism in this species (132L) [42,53,55,66].…”

“…Codon 177 (Asn or Thr) is in the neighbourhood of codon 171 which again is associated with scrapie. Codon 226 (Gln or Glu) is adjacent to codon 225, which has been associated with CWD susceptibility [53] and close to codon 222, which is proposed to enhance resistance to scrapie in goats [3,92]. It remains to be seen whether these differences can give some protection for the transmission of TSE between species.…”