Strain fidelity of chronic wasting disease upon murine adaptation

UniversitätsSpital Zürich, Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland; Department of Molecular Pathology, Medical University Lodz, Czechoslowacka Street 8/10, Pl 92-216 Lodz, Poland; Department of Microbiology, Immunology, and Pathology, Colorado State University, 200 W Lake Street. Campus Delivery 1619, Fort Collins, Colorado, 80523-1619 USA; Institute of Molecular Biology and Biophysics, HPK G4, ETH Zurich, CH-8093 Zürich, Switzerland; Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, Colorado 80526-2097, USA

^* To whom correspondence should be addressed. Email: adriano.aguzzi{at}usz.ch.

	Abstract

Chronic wasting disease (CWD), a prion disease of deer and elk, is highly prevalent in some regions of North America. The establishment of mouse-adapted CWD prions has proven difficult due to the strong species barrier between mice and deer. Here we report efficient transmission of CWD to transgenic mice overexpressing murine PrP. All mice developed disease 500±62 days after intracerebral CWD challenge. The incubation period decreased to 228±103 on secondary passage and to 162±6 days on tertiary passage. Mice developed very large, radially-structured cerebral amyloid plaques similar to those of CWD-affected deer and elk. PrP^Sc was detected in spleen, indicating that murine CWD was lymphotropic. PrP^Sc glycoform profiles maintained a predominantly diglycosylated PrP pattern, as seen in CWD in deer and elk, across all passages. Therefore, all pathological, biochemical and histological strain characteristics of CWD appear to persist upon repetitive serial passage through mice. These findings indicate that the salient strain-specific properties of CWD are encoded by agent-intrinsic components rather than by host factors.