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

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 characte...

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Autores: Vidal, Enric, López Lorenzo, Nuria, Rodríguez Requena, Jesús, Castilla, Joaquín
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:dnet:minerva_____::7346a852dae7cb81f8438fbd450683b5
Acesso em linha:https://hdl.handle.net/10347/47160
Access Level:acceso abierto
Palavra-chave:Chronic wasting disease
Glycosylation
Prion
Prion strains
Transmissible spongiform encephalopathies
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spelling Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoringVidal, EnricLópez Lorenzo, NuriaRodríguez Requena, JesúsCastilla, JoaquínChronic wasting diseaseGlycosylationPrionPrion strainsTransmissible spongiform encephalopathiesPrion 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.ElsevierUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina20252025-04-1120252025-04-11journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/47160reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-122201OB-C21 ANALISIS DEL MALPLEGAMIENTO IN VITRO DE UNA DIVERSIDAD DE PROTEINAS DEL PRION PARA LA GENERACION DE NUEVAS ENTIDADES INFECCIOSAS Y DESARROLLO DE APROXIMACIONES TERAPEUTICASAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-122201OB-C21 DESARROLLO DE INNOVADORES MODELOS DE ENFERMEDADES PRIONICAS Y ESTUDIO DE LA PATOBIOLOGIA DE PRIONES SINTETICOS EN RATONES TRANSGENICOS Y HOSPEDADORES POCO COMUNES.Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) AC21_2%2F00024 BIOMARCADORES PRODROMICOS EN INSOMNIO FAMILIAR LETAL: UN ESTUDIO LONGITUDINAL EN HUMANOS Y RATONESopen accesshttp://purl.org/coar/access_right/c_abf2© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:minerva_____::7346a852dae7cb81f8438fbd450683b52026-06-15T12:47:27Z
dc.title.none.fl_str_mv Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
title Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
spellingShingle Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
Vidal, Enric
Chronic wasting disease
Glycosylation
Prion
Prion strains
Transmissible spongiform encephalopathies
title_short Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
title_full Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
title_fullStr Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
title_full_unstemmed Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
title_sort Conservation of strain properties of bank vole-adapted chronic wasting disease in the absence of glycosylation and membrane anchoring
dc.creator.none.fl_str_mv Vidal, Enric
López Lorenzo, Nuria
Rodríguez Requena, Jesús
Castilla, Joaquín
author Vidal, Enric
author_facet Vidal, Enric
López Lorenzo, Nuria
Rodríguez Requena, Jesús
Castilla, Joaquín
author_role author
author2 López Lorenzo, Nuria
Rodríguez Requena, Jesús
Castilla, Joaquín
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)
Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
dc.subject.none.fl_str_mv Chronic wasting disease
Glycosylation
Prion
Prion strains
Transmissible spongiform encephalopathies
topic Chronic wasting disease
Glycosylation
Prion
Prion strains
Transmissible spongiform encephalopathies
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-04-11
2025
2025-04-11
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/47160
url https://hdl.handle.net/10347/47160
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-122201OB-C21 ANALISIS DEL MALPLEGAMIENTO IN VITRO DE UNA DIVERSIDAD DE PROTEINAS DEL PRION PARA LA GENERACION DE NUEVAS ENTIDADES INFECCIOSAS Y DESARROLLO DE APROXIMACIONES TERAPEUTICAS
Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-122201OB-C21 DESARROLLO DE INNOVADORES MODELOS DE ENFERMEDADES PRIONICAS Y ESTUDIO DE LA PATOBIOLOGIA DE PRIONES SINTETICOS EN RATONES TRANSGENICOS Y HOSPEDADORES POCO COMUNES.
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) AC21_2%2F00024 BIOMARCADORES PRODROMICOS EN INSOMNIO FAMILIAR LETAL: UN ESTUDIO LONGITUDINAL EN HUMANOS Y RATONES
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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