Location: Virus and Prion ResearchTitle: Role of donor genotype in RT-QuIC seeding activity of chronic wasting disease prions using human and bank vole substrates
Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2019
Publication Date: 1/7/2020
Citation: Hwang, S., Greenlee, J.J., Nicholson, E.M. 2020. Role of donor genotype in RT-QuIC seeding activity of chronic wasting disease prions using human and bank vole substrates. Scientific Reports. 15(1):e0227487. https://doi.org/10.1371/journal.pone.0227487.
Interpretive Summary: Prion diseases are fatal neurodegenerative diseases that affect a wide range of livestock and wildlife. The disease process occurs through the misfolding of a normally occuring protein. A recently developed approach for the detection of this misfolded protein uses a technique referred to as Real-time quaking induced conversion (RT-QuIC). RT-QuIC amplifies the amount of misfolded protein available for detection and has been used to differentiate prion diseases through differences in the rate of misfolding. In this work we present a comparison of the relative rates of misfolding in RT-QuIC from different sources of chronic wasting disease using both human and bank vole prion protein as the substrate for amplification. Regardless of the chronic wasting disease source and genotype, the bank vole substrate was equivalently sensitive indicating the utility of this substrate for the detection of CWD regardless of host or genotype. Similarly with human prion protein substrate no differences found indicating that at the level of conversion of the human prion protein to the fibril form conformation all tested CWD isolates are equivalent.
Technical Abstract: Chronic wasting disease is a transmissible spongiform encephalopathy of cervids. This fatal neurodegenerative disease is caused by misfolding of the cellular prion protein (PrPC) to pathogenic conformers (PrPSc), and the pathogenic forms accumulate in the brain and other tissues. Real-time Quaking Induced Conversion (RT-QuIC) can be used for the detection of prions and for prion strain discrimination in a variety of biological tissues from humans and animals. In this study, we evaluated how either PrPSc from cervids of different genotypes or PrPSc from different sources of CWD influence the fibril formation of recombinant bank vole (BV) or human prion proteins using RT-QuIC. We found that reaction mixtures seeded with PrPSc from different genotypes of white-tailed deer or reindeer brains have similar conversion efficiency with both substrates. Also, we observed similar results when assays were seeded with different sources of CWD. Thus, we conclude that the genotypes of all sources of CWD used in this study do not influence the level of conversion of PrPC to PrPSc.