In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies

BMC Veterinary Research

Christopher J Johnson²  Haeyoon Chang²  Christina M Carlson¹  Aaron R Morawski³ 

[1] Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI, USA;USGS National Wildlife Health Center, Madison, WI, USA;Present address: National Institutes of Health, 9000 Rockville Pike, Bethesda 20892, Maryland, USA

关键词: Species barrier;    Transmissible mink encephalopathy;    Chronic wasting disease;    Scrapie;    Bighorn sheep;   

Others  :  1119481
DOI  :  10.1186/1746-6148-9-157

 received in 2013-05-01, accepted in 2013-08-02,  发布年份 2013

【 摘 要 】

Background

Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown.

Results

We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A¹³⁶R¹⁵⁴Q¹⁷¹ genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A¹³⁶R¹⁵⁴Q¹⁷¹ genotype sheep.

Conclusions

Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A¹³⁶R¹⁵⁴Q¹⁷¹ genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted. The lack of reported TSEs in BHS may be attributable to other host factors or a lack of TSE surveillance in this species.

【 授权许可】

   
2013 Morawski et al.; licensee BioMed Central Ltd.

【 图 表 】

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