Abstract
Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrPC) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrPC protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.
Highlights
The fatal, neurodegenerative prion diseases, known as transmissible spongiform encephalopathies (TSEs) have been detected in a wide range of species
Some prion diseases transmit between species but this process is relatively inefficient between more distantly related species and this so-called ‘‘species barrier’’ may be to a large extent a PrPC sequence ‘‘compatibility’’ barrier, caused by species specific differences at key amino acids interfering with the PrP conversion and agent replication process [10,11]
In brown bear (Ursus arctos) two PrPC protein variants with different apparent molecular mass were expressed at similar level and both were proteolytically processed; the size variants reflected the two PRNP open reading frames of 249 and 257 amino acids (Table 1)
Summary
The fatal, neurodegenerative prion diseases, known as transmissible spongiform encephalopathies (TSEs) have been detected in a wide range of species. These diseases cannot develop, and the disease agent does not replicate, without the expression of the prion gene (PRNP) encoding the prion protein PrP [1,2]. Normal PrPC is converted into abnormal PrPSc which accumulates as a range of proteasesensitive and –resistant isoforms. This process involves a change in protein conformation but no modification of amino acid sequence. Some prion diseases transmit between species but this process is relatively inefficient between more distantly related species and this so-called ‘‘species barrier’’ may be to a large extent a PrPC sequence ‘‘compatibility’’ barrier, caused by species specific differences at key amino acids interfering with the PrP conversion and agent replication process [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
