Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion
| Autor: | Nicholas J. Haley, Kristen A. Davenport, Jürgen A. Richt, Rachel Rielinger, Katherine I. O'Rourke, Gordon Mitchell |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Amyloid animal diseases Scrapie Biology Plant disease resistance Protein Aggregation Pathological Prion Proteins law.invention 03 medical and health sciences law In vivo Virology medicine Animals Genetic Predisposition to Disease Allele Alleles Genetics Deer Chronic wasting disease medicine.disease In vitro 030104 developmental biology Recombinant DNA Wasting Disease Chronic Research Article |
| Zdroj: | The Journal of general virology. 98(11) |
| ISSN: | 1465-2099 |
| Popis: | In mammals, susceptibility to prion infection is primarily modulated by the host’s cellular prion protein (PrPC) sequence. In the sheep scrapie model, a graded scale of susceptibility has been established both in vivo and in vitro based on PrPC amino acids 136, 154 and 171, leading to global breeding programmes to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrPC allele conferring absolute resistance in cervids has been identified. To model the susceptibility of various naturally occurring and hypothetical cervid PrPC alleles in vitro, we compared the amplification rates and amyloid extension efficiencies of eight distinct CWD isolates in recombinant cervid PrPC substrates using real-time quaking-induced conversion. We hypothesized that the in vitro conversion characteristics of these isolates in cervid substrates would correlate to in vivo susceptibility – permitting susceptibility prediction for the rare alleles found in nature. We also predicted that hypothetical alleles with multiple resistance-associated codons would be more resistant to in vitro conversion than natural alleles with a single resistant codon. Our studies demonstrate that in vitro conversion metrics align with in vivo susceptibility, and that alleles with multiple amino acid substitutions, each influencing resistance independently, do not necessarily contribute additively to conversion resistance. Importantly, we found that the naturally occurring whitetail deer QGAK substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo is warranted. |
| Databáze: | OpenAIRE |
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