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

Vidal, EnricLópez Lorenzo, NuriaRodríguez Requena, JesúsCastilla, Joaquín2026-05-072026-05-072025-04-11Vidal, E., Eraña, H., Charco, J. M., Lorenzo, N. L., Giler, S., Ordóñez, M., Fernández-Muñoz, E., San-Juan-Ansoleaga, M., Telling, G. C., Sánchez-Martín, M. A., Geijo, M., Requena, J. R., & Castilla, J. (2025). Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring. Neurobiology of Disease, 210. https://doi.org/10.1016/J.NBD.2025.106894https://hdl.handle.net/10347/47160Prion 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.eng© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND licenseAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Chronic wasting diseaseGlycosylationPrionPrion strainsTransmissible spongiform encephalopathiesConservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoringjournal article2026-05-0410.1016/J.NBD.2025.1068941095-953Xopen access1095-953X