Genetic Variation and Strain Dynamics in Chronic Wasting Disease

Chronic wasting disease (CWD) is a prion disease of cervids marked by growing strain diversity and variation in host susceptibility. Central to this complexity are prion protein gene (<i>Prnp</i>) polymorphisms, which can modulate pathogenesis by altering the ability of cellular prion protein (PrP^C) to misfold into infectious prions (PrP^Sc), or by promoting the emergence of novel strains. Studies in cervids and transgenic rodent models demonstrate that individual polymorphisms influence PrP stability, conversion efficiency, and the selection of PrP^Sc conformers, with most variants conferring partial resistance but none offering complete protection. These host-strain interactions define transmission barriers and disease phenotype. Understanding how <i>Prnp</i> genotypes shape CWD strain diversity is essential for predicting transmission dynamics, refining surveillance, and assessing zoonotic potential as the disease continues to expand geographically and genetically.