Detection and Discrimination of Classical and Atypical L-type Bovine Spongiform Encephalopathy by Real-Time Quaking-Induced Conversion.

Statutory surveillance of bovine spongiform encephalopathy (BSE) indicates that cattle are susceptible to both classical (C-BSE) and atypical forms of BSE. Atypical forms of BSE appear to be sporadic and thus may never be eradicated. A major challenge for prion surveillance is the lack of sufficiently practical and sensitive tests for routine BSE detection and strain discrimination. The RT-QuIC test, which is based on prion-seeded fibrillization of recombinant prion protein (rPrPSen), is known to be highly specific and sensitive for detection of multiple human and animal prion diseases, but not BSE. Here, we tested brain tissue from C-BSE- and atypical L-type bovine spongiform encephalopathy (L-type BSE or L-BSE) affected cattle by RT-QuIC and found that both BSE forms can be detected and distinguished using particular rPrPSen substrates. Specifically, L-BSE was detected using multiple rPrPSen substrates while C-BSE was much more selective. This substrate-based approach suggests a diagnostic strategy for specific, sensitive, and rapid detection and discrimination of at least some BSE forms.