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Review
. 2016;10(1):83-91.
doi: 10.1080/19336896.2015.1118603.

Cross-species transmission of CWD prions

Timothy D Kurt  1 , Christina J Sigurdson  1   2
Affiliations
Review

Cross-species transmission of CWD prions

Timothy D Kurt et al. Prion. 2016.

Abstract

Prions cause fatal neurodegenerative diseases in humans and animals and can be transmitted zoonotically. Chronic wasting disease (CWD) is a highly transmissible prion disease of wild deer and elk that affects cervids over extensive regions of the United States and Canada. The risk of cross-species CWD transmission has been experimentally evaluated in a wide array of mammals, including non-human primates and mouse models expressing human cellular prion protein. Here we review the determinants of cross-species CWD transmission, and propose a model that may explain a structural barrier for CWD transmission to humans.

Keywords: CJD; amyloid; chronic wasting disease; neurodegeneration; prion; zoonotic.

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Figures

FIGURE 1.
FIGURE 1.
Investigating the structural determinants of the CWD-human transmission barrier. The human and elk β2-α2 loop amino acid sequences differ at 4 positions: 166, 168, 170, and 174 (top). Transgenic mice expressing full-length human PrPC (blue) or human PrPC with the elk β2-α2 loop (red) were inoculated intracerebrally with CWD prions. Although mice expressing human PrPC did not develop disease, mice expressing the human-elk loop PrPC [Tg(HuPrPelk166-174)] were susceptible to CWD infection (83%). Inoculation of brain from a CWD-infected Tg(HuPrPelk166-174) mouse into additional transgenic mice transmitted the disease to all Tg(HuPrPelk166-174) mice, but to only 1 of 17 Tg(HuPrP) mice.
FIGURE 2.
FIGURE 2.
Structural models of elk and human side chain packing within the β2-α2 loop may explain CWD transmission barriers. Atomic space-filling models of amino acid side chains within the β2-α2 loop of PrP were modeled as a parallel β-sheet. In this model, the CWD PrPSc and cervid PrPC (top pair) interdigitate in a steric zipper. In contrast, the CWD PrPSc and human PrPC (bottom pair) interaction generates a steric clash (blue rectangle) and a cavity (arrow) that would be incompatible with zipper formation and may explain why CWD does not convert human PrPC. Amino acids common to both cervids and humans are yellow; human-specific residues are green.
See this image and copyright information in PMC

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