Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring

Abstract

Prion disease phenotypes (prion strains) are primarily determined by the specific misfolded conformation of the cellular prion protein (PrPC). However, post-translational modifications, including glycosyl phosphatidyl inositol (GPI) membrane anchoring and glycosylation, may influence strain characteristics. We investigated whether these modifications are essential for maintaining the unique properties of bank vole-adapted Chronic Wasting Disease (CWD-vole), the fastest known prion strain. Using a novel transgenic mouse model expressing I109 bank vole PrPC lacking the GPI anchor and largely devoid of glycans, we performed serial passages of CWD-vole prions. Despite elongated initial incubation periods, the strain maintained 100 % attack rate through three passages. Although the pathological phenotype showed characteristic GPI-less features, including abundant extracellular plaque formation, three subsequent serial passages in fully glycosylated and GPI-anchored bank vole I109 PrPC expressing transgenic mice TgVole (1×) demonstrated that the strain's distinctive rapid propagation properties were preserved. These findings suggest that neither GPI anchoring nor glycosylation are essential for maintaining CWD-vole strain properties, supporting the concept that strain characteristics are primarily encoded in the protein's misfolded structure.