Abstract
In animal prion diseases, including bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in cervids, and scrapie in sheep and goats, a disease-associated isoform of prion protein (PrPd) accumulates in the brains of affected animals. Although the CH1641 scrapie isolate was experimentally established in the UK, a few natural CH1641-like scrapie cases have been reported in France and the UK. The molecular mass of the unglycosylated protease-resistant core of PrPd (PrPres) is known to be similar between CH1641-like scrapie and experimental BSE in sheep. We previously established an experimental CH1641-like scrapie isolate (Sh294) from a natural classical scrapie case. Here, we demonstrated that the Sh294 isolate was independent of both classical and atypical BSEs by cross-species transmission to bovine PrP overexpressing (TgBoPrP) mice and wild-type mice. Interestingly, we found that the Sh294 isolate altered its host range by the transmission to TgBoPrP mice, and we succeeded in the first stable reproduction of CH1641-like scrapie specific PrPres banding patterns with the ~12-kDa small C-terminal fragment in wild-type mice. This study provides new insight into the relationship between CH1641-like scrapie isolates and BSEs. In addition, interspecies transmission models such as we have demonstrated here could be a great help to investigate the origin and host range of animal prions.
Highlights
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders that affect both humans and animals [1]
TgBoPrP mice infected with Sh294 exhibited clinical signs and the triplet band pattern of protease-resistant core of PrPd (PrPres) similar to those of mice infected with L-Bovine spongiform encephalopathy (BSE)
The mean survival periods, lesion profiles, and diseaseassociated PrP (PrPd) distribution patterns in the brain were distinctly different between the mice infected with Sh294 and those infected with L-BSE
Summary
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders that affect both humans and animals [1]. Prion diseases are characterized by spongiform changes and accumulation of a disease-associated isoform of prion protein (PrPd), which is generated by post-transcriptional modification of host cellular prion protein (PrPC), in the brains of affected hosts [2]. Bovine spongiform encephalopathy (BSE) is a prion disease in cattle [4] that was first identified in the UK and spread to European as well as North American countries and Japan through feeding of BSE-contaminated meat and bone meal [5]. To test the scrapie origin hypothesis, several experimental transmissions of classical scrapie isolates to cattle have been performed in the USA and UK [9–13]. The biochemical and pathological properties of accumulated P rPd in the brains of cattle
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