Transmission of CWD from White-tailed Deer (Odocoileus virginianus), to Elk Transgenic Mice Results in Modifications to the Infectious Prion Open Access

Interspecies Prion Transmission;Chronic Wasting Disease;CWD Strains

Narayan, Jeffrey P ; McKenzie, Debbie (Biological Sciences)Aiken, Judd (Agricultural, Life and Environmental Sciences) ; Uwiera, Richard (Agricultural, Life and Environmental Sciences) ;

University of Alberta

DOI  :  10.7939/R30K26Q0C
Others  :  https://era.library.ualberta.ca/files/cx633f140t/Narayan_Jeffrey_P_201701_MSc.pdf

美国|英语

来源: Education and Research Archive

【 摘 要 】

Prion diseases are a class of fatal, neurodegenerative disorders resulting from a protein-misfolding event. Of particular concern is chronic wasting disease (CWD), a naturally occurring prion disease affecting cervids; this disease is prevalent in North America and is expanding its host range and geographic distribution. The full extent of CWD strains and the basis behind emergence of new strain properties is incompletely understood. Previously believed to be a single entity, recent evidence supports the idea that CWD can be attributed to several prion strains, which can be distinguished through passage between hosts of differing PRNP genotypes. This study explores interspecies CWD transmission between white-tailed deer (WTD) and elk. I hypothesize that passage of WTD CWD into elk results in a modified infectious prion. To explore this, mice expressing elk PRNP were challenged with CWD prions from elk, or from deer with four different PrP alleles (Wt/Wt, Wt/S96, Wt/H95, H95/S96). 100% penetrance in the mouse model was observed with all CWD isolates examined. Incubation periods varied depending on source material, with Wt/H95, Wt/S96 and H95/S96 showing extensions compared to those of elk and Wt/Wt CWD. Lesion profile analysis showed widespread vacuolation with elk CWD, however, regional differences were observed with WTD CWD. Accumulation of disease-associated PrP (PrPd) appears extensive and severe in TgElk challenged with elk CWD. The WTD isolates resulted in accumulation of PrPd of various densities, however, staining was localized to neuroanatomical regions that differed between CWD isolates. In the cervid prion cell assay (CPCA), Wt/H95 CWD isolate had higher spot counts than the other WTD isolates, comparable to elk CWD. This in vitro infectivity analysis demonstrated differences in susceptibility of cells to CWD agent from one host species, demonstrating variability in virulence between the isolates, lending support to the presence of a strain mixture. In characterizing H95/S96 isolate properties; three distinct patterns in neuropathology and PrPd deposition were identified. These passage lines were individually analyzed and differences were also observed in CPCA spot count. Taken together, these data demonstrate that the infectious agent known as CWD is not a single agent, but can be attributed to many different CWD strains, and that through interspecies transmission novel properties can be attributed to the replicated agent