Association of chronic wasting disease susceptibility with prion protein variation in white-tailed deer (Odocoileus virginianus)

Abstract Chronic wasting disease (CWD) is a fatal, highly transmissible spongiform encephalopathy caused by an infectious prion protein. CWD is spreading across North American cervids. Studies of the prion protein gene (PRNP) in white-tailed deer (WTD; Odocoileus virginianus) have identified non-synonymous substitutions associated with reduced CWD frequency. Because CWD is spreading rapidly geographically, it may impact cervids of conservation concern. Here, we examined the genetic vulnerability to CWD of 2 subspecies of WTD: the endangered Florida Key deer (O. v. clavium) and the threatened Columbian WTD (O. v. leucurus). In Key deer (n = 48), we identified 3 haplotypes formed by 5 polymorphisms, of which 2 were non-synonymous. The polymorphism c.574G>A, unique to Key deer (29 of 96 chromosomes), encodes a non-synonymous substitution from valine to isoleucine at codon 192. In 91 of 96 chromosomes, Key deer carried c.286G>A (G96S), previously associated with substantially reduced susceptibility to CWD. Key deer may be less genetically susceptible to CWD than many mainland WTD populations. In Columbian WTD (n = 13), 2 haplotypes separated by one synonymous substitution (c.438C>T) were identified. All of the Columbian WTD carried alleles that in other mainland populations are associated with relatively high susceptibility to CWD. While larger sampling is needed, future management plans should consider that Columbian WTD are likely to be genetically more vulnerable to CWD than many other WTD populations. Finally, we suggest that genetic vulnerability to CWD be assessed by sequencing PRNP across other endangered cervids, both wild and in captive breeding facilities.

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Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) infected with chronic wasting disease

Journal of General Virology ◽

10.1099/vir.0.81777-0 ◽

2006 ◽

Vol 87 (11) ◽

pp. 3443-3450 ◽

Cited By ~ 41

Author(s):

Jean E. Jewell ◽

Jeremy Brown ◽

Terry Kreeger ◽

Elizabeth S. Williams

Keyword(s):

Western Blot ◽

Odocoileus Virginianus ◽

Prion Protein ◽

Cervus Elaphus ◽

Chronic Wasting Disease ◽

Striated Muscle ◽

Mule Deer ◽

Spongiform Encephalopathy ◽

Wasting Disease ◽

Cervus Elaphus Nelsoni

To investigate the possible presence of disease-associated prion protein (PrPd) in striated muscle of chronic wasting disease (CWD)-affected cervids, samples of diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus elaphus nelsoni) and moose (Alces alces shirasi) were examined by ELISA, Western immunoblot and immunohistochemistry (IHC). PrPd was detected in samples of heart muscle from seven of 16 CWD-infected white-tailed deer, including one free-ranging deer, and in 12 of 17 CWD-infected elk, but not in any of 13 mule deer samples, nor in the single CWD-infected moose. For white-tailed deer, PrPd was detected by Western blot at multiple sites throughout the heart; IHC results on ventricular sections of both elk and white-tailed deer showed positive staining in cardiac myocytes, but not in conduction tissues or nerve ganglia. Levels of PrPd in cardiac tissues were estimated from Western blot band intensity to be lower than levels found in brain tissue. PrPd was not detected in diaphragm, triceps brachii, semitendinosus, latissiumus dorsi or tongue muscles for any of the study subjects. This is the first report of PrPd in cardiac tissue from transmissible spongiform encephalopathy-infected ruminants in the human food chain and the first demonstration by immunological assays of PrPd in any striated muscle of CWD-infected cervids.

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Large‐scale prion protein genotyping in Canadian caribou populations and potential impact on chronic wasting disease susceptibility

Molecular Ecology ◽

10.1111/mec.15602 ◽

2020 ◽

Vol 29 (20) ◽

pp. 3830-3840

Author(s):

Maria Immaculata Arifin ◽

Antanas Staskevicius ◽

Su Yeon Shim ◽

Yuan‐Hung Huang ◽

Heather Fenton ◽

...

Keyword(s):

Prion Protein ◽

Large Scale ◽

Disease Susceptibility ◽

Chronic Wasting Disease ◽

Wasting Disease ◽

Potential Impact

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Detection by real-time quaking-induced conversion (RT-QuIC), ELISA, and IHC of chronic wasting disease prion in lymph nodes from Pennsylvania white-tailed deer with specific PRNP genotypes

Journal of Veterinary Diagnostic Investigation ◽

10.1177/10406387211021411 ◽

2021 ◽

pp. 104063872110214

Author(s):

Deepanker Tewari ◽

David Steward ◽

Melinda Fasnacht ◽

Julia Livengood

Keyword(s):

Real Time ◽

Disease Susceptibility ◽

Chronic Wasting Disease ◽

Low Frequency ◽

The United States ◽

Detection Methods ◽

Spongiform Encephalopathy ◽

Wasting Disease ◽

Diagnostic Laboratory ◽

Highly Sensitive

Chronic wasting disease (CWD) is a prion-mediated, transmissible disease of cervids, including deer ( Odocoileus spp.), which is characterized by spongiform encephalopathy and death of the prion-infected animals. Official surveillance in the United States using immunohistochemistry (IHC) and ELISA entails the laborious collection of lymphoid and/or brainstem tissue after death. New, highly sensitive prion detection methods, such as real-time quaking-induced conversion (RT-QuIC), have shown promise in detecting abnormal prions from both antemortem and postmortem specimens. We compared RT-QuIC with ELISA and IHC for CWD detection utilizing deer retropharyngeal lymph node (RLN) tissues in a diagnostic laboratory setting. The RLNs were collected postmortem from hunter-harvested animals. RT-QuIC showed 100% sensitivity and specificity for 50 deer RLN (35 positive by both IHC and ELISA, 15 negative) included in our study. All deer were also genotyped for PRNP polymorphism. Most deer were homozygous at codons 95, 96, 116, and 226 (QQ/GG/AA/QQ genotype, with frequency 0.86), which are the codons implicated in disease susceptibility. Heterozygosity was noticed in Pennsylvania deer, albeit at a very low frequency, for codons 95GS (0.06) and 96QH (0.08), but deer with these genotypes were still found to be CWD prion-infected.

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Efficient In Vitro Amplification of Chronic Wasting Disease PrPRES

Journal of Virology ◽

10.1128/jvi.00635-07 ◽

2007 ◽

Vol 81 (17) ◽

pp. 9605-9608 ◽

Cited By ~ 71

Author(s):

Timothy D. Kurt ◽

Matthew R. Perrott ◽

Carol J. Wilusz ◽

Jeffrey Wilusz ◽

Surachai Supattapone ◽

...

Keyword(s):

Transgenic Mice ◽

Prion Protein ◽

Protein Misfolding ◽

Chronic Wasting Disease ◽

Body Fluids ◽

The Body ◽

Wasting Disease ◽

Highly Efficient ◽

Significant Step

ABSTRACT Chronic wasting disease (CWD) of cervids is associated with conversion of the normal cervid prion protein, PrPC, to a protease-resistant conformer, PrPCWD. Here we report the use of both nondenaturing amplification and protein-misfolding cyclic amplification (PMCA) to amplify PrPCWD in vitro. Normal brains from deer, transgenic mice expressing cervid PrPC [Tg(cerPrP)1536 mice], and ferrets supported amplification. PMCA using normal Tg(cerPrP)1536 brains as the PrPC substrate produced >6.5 × 109-fold amplification after six rounds. Highly efficient in vitro amplification of PrPCWD is a significant step toward detection of PrPCWD in the body fluids or excreta of CWD-susceptible species.

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