AD.47: Polymorphic variations in cervid prion protein affect CWD agent properties
AD.47: Polymorphic variations in cervid prion protein affect CWD agent
properties
Camilo Duque-Velasquez,1 Allen Herbst1 Chiye Kim,1 Chad Johnson,2 Judd
Aiken1 and Debbie McKenzie1 'Centre for Prions and Protein Folding Diseases;
University of Alberta; Edmonton, AB Canada; 2Soil Sciences Department;
University of Wisconsin; Madison, WI USA
Chronic wasting disease (CWD) is a prion disease of free ranging and farmed
cervids of North America. Similar to other prion diseases, such as sheep Scrapie
and bovine spongiform encephalopathy, it appears there are isolates of CWD with
distinct biological properties (i.e., strains).
Experimental evidence has confirmed the link between variations in the
primary structure of the prion protein, PrPres properties and differential
susceptibility to prion infection.
Given the variability of the amino acid sequence of the prion protein in
cervids and the contagious nature of the disease, there is a likelihood of
continuous agent adaptation. As a result, CWD strains circulating within
heterogeneous cervid populations might be subjected to structural variations,
when replicating in polymorphic PRNP genotypes, affecting strain-specific
biological and physico-chemical properties.
We have previously shown that PRNP polymorphisms Q95G96 (wt), H95G96 (H95)
and Q95S96 (S96) influence susceptibility to CWD in free-ranging white-railed
deer.'
Oral infection of white-tailed deer of known PRNP genotypes (with inoculum
from CWD-positive wt/wt deer) confirmed the link between prion protein primary
sequence, disease progression and PrPCWD properties.2 Deer homozygous for wt
alleles had the shortest incubation period, while heterogeneity of the PRNP
alleles resulted in differential extension of the incubation period: wt/S96 >
wt/H95 > H95/S96. Interestingly, biochemical and structural properties of the
proteinase K-res PrPCWD of wt/H95 and wt/S96 isolates resemble the wt/wt
profile. CWD from deer heterozygous for H95/S96 exhibited distinct properties,
suggesting that this isolate might be a unique CWD strain.
Inoculation of transgenic (tg) mice expressing wt and S96 alleles with CWD
isolates of defined PRNP genotype resulted in 100% attack rates for tg mice
expressing the wt allele. S96 tg mice succumbed with CWD only when inoculated
with isolates from wt/H95 and H95/S96 deer. Since infection of these transgenic
lines with CWD isolates from Colorado/Wyoming suggested that S96 polymorphism
conferred resistance to develop CWD infection3 our data further suggests that
CWD prions containing H95 PrP, expand their tropism to infect resistant
genotypes while maintaining tropism for the original host genotype. Given that
CWD endemic zones are geographical areas where different cervids species might
overlap their niches, some PRNP alleles might facilitate inter-and intra-species
CWD transmission.
References
1. Johnson C. Johnson J. Vanderloo JP, Keane D, Aiken JM, McKenzie D. Prion
protein polymorphisms in white-tailed deer influence susceptibility to chronic
wasting disease. J Gen Virol 2006; 87:2109-14: PMID:16760415; http://dx.doi.org/10.1099/vir.0.81615-0
2. Johnson CJ, Herbst A. Duque-Velasquez C, Vanderloo JP. Bochsler P.
Chappell R, et al. Prion protein polymorphisms affect chronic wasting disease
progression. PLoS One 2011; 6:e17450; PMID:21445256: http://dx.doi.org/10.1371/journal.pone.0017450
3. Meade-White K, Race B, Trifilo M, Bossers A, Favara C. Lacasse R. et al.
Resistance to chronic wasting disease in transgenic mice expressing a naturally
occurring allelic variant of deer prion protein. J Virol 2007; 81 :4533-9; PMID:
17314157; http://dx.doi.org/10.1128/JVI.02762-06
TSS
posted by Terry S. Singeltary Sr. at
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