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Alteration of the chronic wasting disease species barrier by in vitro prion amplification

Journal of Virology
By: , and 

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Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids now detected in 19 states of the United States, three Canadian provinces, and South Korea. Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is not known. To investigate this issue, we previously used serial protein misfolding cyclic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several species sympatric with cervids, including prairie voles (Microtus ochrogaster) and field mice (Peromyscus spp.). Here, we show that prairie voles are susceptible to mule deer CWD prions in vivo and that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD for this species. Prairie voles inoculated with sPMCA products developed clinical signs of TSE disease approximately 300 days prior to, and more consistently than, those inoculated with CWD prions from deer brain. Moreover, the deposition patterns and biochemical properties of protease-resistant form of PrP (PrPRES) in the brains of affected voles differed from those in cervidized transgenic (CerPrP) mice infected with CWD. In addition, voles inoculated orally with sPMCA products developed clinical signs of TSE and were positive for PrPRES deposition, whereas those inoculated orally with deer-origin CWD prions did not. These results demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determinants of prion species barriers.

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Additional publication details

Publication type Article
Publication Subtype Journal Article
Title Alteration of the chronic wasting disease species barrier by in vitro prion amplification
Series title Journal of Virology
Volume 85
Issue 17
Year Published 2011
Language English
Publisher American Society for Microbiology
Publisher location Washington, D.C.
Contributing office(s) National Wildlife Health Center
Description 10 p.
Larger Work Type Article
Larger Work Subtype Journal Article
Larger Work Title Journal of Virology
First page 8528
Last page 8537
Online Only (Y/N) N
Additional Online Files (Y/N) N