Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP

Authors: WILSON, RONA - Roslin Institute; PLINSTON, CHRIS - Roslin Institute; HUNTER, NORA - University Of Edinburgh; CASALONE, CRISTINA - Institute Of Experimental Zooprofilattic; CORONA, CRISTIANO - Institute Of Experimental Zooprofilattic; TAGLIAVINI, FABRIZIO - Carlo Besta Neurological Institute; SUARDI, SILVIA - Carlo Besta Neurological Institute; RUGGERONE, MARGHERITA - Carlo Besta Neurological Institute; MODA, FABIO - Carlo Besta Neurological Institute; GRAZIANO, SILVIA - Istituto Superiore Di Sanita; SBRICCOLI, MARCO - Istituto Superiore Di Sanita; CARDONE, FRANCO - Istituto Superiore Di Sanita; POCCHIARI, MAURIZIO - Istituto Superiore Di Sanita; INGROSSO, LOREDANA - Istituto Superiore Di Sanita; BARON, THIERRY - French Agency Of Food Security And Sanitation; Richt, Juergen; ANDREOLETTI, OLIVIER - Ecole Nationale; SIMMONS, MARION - Veterinary Laboratories Agency (VLA); LOCKEY, RICHARD - Veterinary Laboratories Agency (VLA); MANSON, JEAN - Roslin Institute; BARRON, RONA - University Of Edinburgh

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/2012
Publication Date: 7/1/2012
Citation: Wilson, R., Plinston, C., Hunter, N., Casalone, C., Corona, C., Tagliavini, F., Suardi, S., Ruggerone, M., Moda, F., Graziano, S., Sbriccoli, M., Cardone, F., Pocchiari, M., Ingrosso, L., Baron, T., Richt, J., Andreoletti, O., Simmons, M., Lockey, R., Manson, J.C., Barron, R.M. 2012. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein. Journal of General Virology. 93(Pt 7):1624-1629.

Interpretive Summary: Bovine spongiform encephalopathy (BSE), a neurodegenerative disease of cattle, scrapie, a neurodegenerative disease of sheep, and chronic wasting disease (CWD), a neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, are each a transmissible spongiform encephalopathy (TSE). The association between BSE and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle TSEs can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. Since the emergence of the feedborne BSE epidemic in Europe, rare atypical forms of BSE in cattle and atypical scrapie in sheep have been identified in several countries around the world. The public health community has been concerned about the risk posed to humans by these atpyical agents, as well as CWD. The data in this report strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans. In this report, an international team of scientists inoculated two forms of atypical BSE (BASE and H-type), several isolates of atypical scrapie, and one isolate of CWD from a white-tailed deer into a panel of three lines of transgenic mice expressing human, bovine, or mouse prions. The human lines of transgenic mice represent the genetic diversity for prions in the human population (HuMM, HuMV and HuVV). In humans this genetic diversity correlates with human susceptibility to TSE in that all confirmed clinical cases of vCJD to date have occurred in individuals who carry two copies of the allele encoding methionine (M) instead of valine (V) at the human prion amino acid position 129. The other mice were included as study controls. Upon challenge with these ruminant TSEs, the transgenic mice expressing human PrP did not show any signs of disease pathology. This is good news because the findings strongly suggest the presence of a substantial transmission barrier preventing transmission of CWD or atypical ruminant TSEs to humans. This information is important for producers of sheep, cattle, and cervids, as well as for regulatory and public health officials managing TSE disease eradication and control policies.

Technical Abstract: The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle TSEs can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several new TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate, and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.