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 (Prnp) 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 Prnp 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.

Prion diseases are fatal neurodegenerative disorders that affect humans and animals, caused by the conformational conversion of the normal cellular prion protein (PrP^C) into its misfolded, infectious isoform PrP^Sc. Recently, camel prion disease (CPrD) was identified in dromedary camels (Camelus dromedarius) in Algeria. Due to the potential implications for animal and human health, as well as the possible socio-economic impact in Mediterranean regions where camels play a pivotal role as a source of food, in-depth characterization of camel prions is important to increase our understanding of camel prion disease. We developed a neuronal cell line model for studying the molecular features of camel prion infection. We genetically edited mouse neuronal CAD5 cells to generate CAD5 PrP knockout (KO) cells. We then used lentiviral transduction to generate CAD5 cells expressing camel PrP (CAD5-camel-PrP). Following infection of these cells with a CPrD-positive camel brain homogenate, we observed PrP^Sc signals at various passages, as indicated by immunoblotting analysis. RT-QuIC (Real-Time Quaking-Induced Conversion) assays further supported these findings, demonstrating transient prion conversion activity in the CPrD-infected CAD5-camel-PrP cells. Taken together, our data describe the first neuronal cell line permissive to camel prion infection, a novel in vitro tool for mechanistic studies of camel prion disease.