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United States Department of Agriculture

Agricultural Research Service

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Title: Assessment of direct and indirect transmission of CWD from three cervid species to humans

Authors
item Zheng, Mengjie - CASE WESTERN RESERVE UNIV
item Qing, Liuting - CASE WESTERN RESERVE UNIV
item Huang, Shenghai - CASE WESTERN RESERVE UNIV
item Chen, Fusong - CASE WESTERN RESERVE UNIV
item Wang, Meiling - CASE WESTERN RESERVE UNIV
item Wang, Lan - CASE WESTERN RESERVE UNIV
item Miller, Michael - COLORADO DIV OF WILD LIFE
item Hamir, Amirali
item Richt, Juergen
item O'Rourke, Katherine
item Belay, Ermias - CDC, NCID, ATLANTA, GA
item Schonberger, Lawrence - CDC, NCID, ATLANTA, GA
item Gambetti, Pierluigi - CASE WESTERN RESERVE UNIV
item Kong, Qingzhong - CASE WESTERN RESERVE UNIV

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: September 26, 2007
Publication Date: September 26, 2007
Citation: Zheng, M., Qing, L., Huang, S., Chen, F., Wang, M., Wang, L., Miller, M., Hamir, A.N., Richt, J.A., O'Rourke, K., Belay, E.D., Schonberger, L.B., Gambetti, P., Kong, Q. 2007. Assessment of direct and indirect transmission of CWD from three cervid species to humans [abstract]. Prion 2007. Paper No. FC5.8.

Technical Abstract: Chronic wasting disease (CWD) is the prion disease widespread in cervids (white-tailed deer, mule deer, elk, and moose). The presence of significant prion infectivity reported in the muscles of CWD-affected cervids indicates that people who had consumed venison from CWD-affected animals in the United States and elsewhere may have been exposed to CWD. In order to determine whether the CWD prion, like the bovine spongiform encephalopathy, is transmissible from cervids to humans, cervidized transgenic mice (Tg12) and humanized transgenic mice (Tg1 and Tg40) were created, which express the elk prion protein (PrP) and human PrP in a mouse PrP-null background respectively. The cervidized Tg12 mice intracerebrally inoculated with CWD isolates from elk, mule deer, and white-tailed deer became infected with relatively short average incubation times (118±6 days for elk 1, 142±7 days for elk 2, 187±18 days for mule deer, and 180±3 days for white-tailed deer). The humanized Tg40 mice and Tg1 mice similarly inoculated with human sCJDMM1 became infected with an average incubation time of 263±13 days for Tg40 mice and 266±5 days for Tg1 mice. In contrast, all of the humanized transgenic mice intracerebrally inoculated with CWD isolates from the three cervid species failed to develop the hallmarks of CWD throughout their natural lifespan. Since the host range of a prion strain could change after adaptation in another species and CWD has been transmitted to cattle and sheep after experimental inoculation, humanized and cervidized Tg mice were also inoculated with cattle- or sheep-adapted CWD, but the mice failed to become infected so far. Our data point to the existence of a significant species barrier between CWD and humans, which may strongly limit the human transmissibility of CWD.

Last Modified: 10/21/2014
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