Relationships between PrPSc Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System

• DOI: 10.1371/journal.pone.0043060
• Publication Date: 2012-08-14T21:21:38Z
• Authors: Catherine E. Vrentas; Justin J. Greenlee; Trudy L. Tatum; Eric M. Nicholson
• Keywords: Incubation period

Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of cellular prion protein (PrPC) into a â-rich conformer (PrPSc) that accumulates higher-order structures brain and other tissues. Distinct strains TSEs exist, characterized different pathologic profiles upon passage rodents representing distinct conformations PrPSc. One biochemical method distinguishing is stability PrPSc as determined unfolding guanidine hydrochloride (GdnHCl), which tightly positively correlated with incubation time disease mice. Here, we utilize rapid, protease-free version assay to characterize naturally occurring samples, fast-acting inoculum for highly dependent on amino acid at codon 136 protein. We methodology identify presence two isolates inoculum, compare isolate properties those host-stabilized reference (NADC 13-7) order assess stability/incubation correlation natural host system. demonstrate utility characterizing TSE throughout serial livestock, applicable range systems, bovine encephalopathy chronic wasting disease.