RT Journal Article
T1 Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
A1 Vidal, Enric
A1 López Lorenzo, Nuria
A1 Rodríguez Requena, Jesús
A1 Castilla, Joaquín
K1 Chronic wasting disease
K1 Glycosylation
K1 Prion
K1 Prion strains
K1 Transmissible spongiform encephalopathies
AB 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.
PB Elsevier
YR 2025
FD 2025-04-11
LK https://hdl.handle.net/10347/47160
UL https://hdl.handle.net/10347/47160
LA eng
NO Vidal, 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.2025.106894
NO The present work was partially funded by three different grants awarded by \u201CAgencia Estatal de Investigaci\u00F3n, Ministerio de Ciencia e Innovaci\u00F3n\u201D (Spanish Government), grant numbers PID2021-122201OB-C21 and PID2021-1222010B-C22, and co-financed by the European Regional Development Fund (ERDF). EFA031/01 NEURO-COOP, which is co-funded at 65 % by the European Union through Programa Interreg VI-A Espa\u00F1a-Francia-Andorra (POCTEFA 2021\u20132027). Additional funding was provided by the Instituto de Salud Carlos III (ISCIII), grant number AC21_2/00024 as member of a JPND grant JPND-2021-650-130. Additionally, CICbioGUNE currently holds a Severo Ochoa Excellence accreditation, CEX2021-001136-S, also funded by MCIN/AEI/10.13039/501100011033. Transgenic Facility, directed by M.A. S-M, is supported by Instituto de Salud Carlos III (ISCIII), co-funded by the European Union grant PT23/00123. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
DS Minerva
RD 9 jun 2026