International Journal of Molecular Sciences Review Cervid Prion Protein Polymorphisms: Role in Chronic Wasting Disease Pathogenesis Maria Immaculata Arifin 1,2,3, Samia Hannaoui 1,2,3, Sheng Chun Chang 1,2,3, Simrika Thapa 1,2,3, Hermann M. Schatzl 1,2,3 and Sabine Gilch 1,2,3,* 1 Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; maria.arifi
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[email protected] (H.M.S.) 2 Calgary Prion Research Unit, University of Calgary, Calgary, AB T2N 4N1, Canada 3 Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada * Correspondence:
[email protected] Abstract: Chronic wasting disease (CWD) is a prion disease found in both free-ranging and farmed cervids. Susceptibility of these animals to CWD is governed by various exogenous and endogenous factors. Past studies have demonstrated that polymorphisms within the prion protein (PrP) sequence itself affect an animal’s susceptibility to CWD. PrP polymorphisms can modulate CWD pathogenesis in two ways: the ability of the endogenous prion protein (PrPC) to convert into infectious prions (PrPSc) or it can give rise to novel prion strains. In vivo studies in susceptible cervids, complemented by studies in transgenic mice expressing the corresponding cervid PrP sequence, show that each polymorphism has distinct effects on both PrPC and PrPSc. It is not entirely clear how these polymor- phisms are responsible for these effects, but in vitro studies suggest they play a role in modifying PrP epitopes crucial for PrPC to PrPSc conversion and determining PrPC stability.