Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein

Autores
Linero, Florencia Natalia; Sepúlveda, Claudia Soledad; Christopoulou, Ioanna; Hulpiau, Paco; Scolaro, Luis Alberto; Saelens, Xavier
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.
Fil: Linero, Florencia Natalia. Flanders Interuniversity Institute For Biotechnology; Bélgica. University of Ghent; Bélgica
Fil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Christopoulou, Ioanna. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgica
Fil: Hulpiau, Paco. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgica
Fil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Saelens, Xavier. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgica
Materia
VHHs
Junín
Arenavirus
Neutralizing
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/94016
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/94016
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neutralization of Junín virus by single domain antibodies targeted against the nucleoproteinLinero, Florencia NataliaSepúlveda, Claudia SoledadChristopoulou, IoannaHulpiau, PacoScolaro, Luis AlbertoSaelens, XavierVHHsJunínArenavirusNeutralizinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.Fil: Linero, Florencia Natalia. Flanders Interuniversity Institute For Biotechnology; Bélgica. University of Ghent; BélgicaFil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Christopoulou, Ioanna. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaFil: Hulpiau, Paco. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaFil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Saelens, Xavier. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaNature Publishing Group2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/94016Linero, Florencia Natalia; Sepúlveda, Claudia Soledad; Christopoulou, Ioanna; Hulpiau, Paco; Scolaro, Luis Alberto; et al.; Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein; Nature Publishing Group; Scientific Reports; 8; 11451; 12-2018; 1-172045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/protocol/10.1007%2F978-1-4939-6981-4_28info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-29508-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:24:49Zoai:ri.conicet.gov.ar:11336/94016instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:24:49.212CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
title Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
spellingShingle Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
Linero, Florencia Natalia
VHHs
Junín
Arenavirus
Neutralizing
title_short Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
title_full Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
title_fullStr Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
title_full_unstemmed Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
title_sort Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
dc.creator.none.fl_str_mv Linero, Florencia Natalia
Sepúlveda, Claudia Soledad
Christopoulou, Ioanna
Hulpiau, Paco
Scolaro, Luis Alberto
Saelens, Xavier
author Linero, Florencia Natalia
author_facet Linero, Florencia Natalia
Sepúlveda, Claudia Soledad
Christopoulou, Ioanna
Hulpiau, Paco
Scolaro, Luis Alberto
Saelens, Xavier
author_role author
author2 Sepúlveda, Claudia Soledad
Christopoulou, Ioanna
Hulpiau, Paco
Scolaro, Luis Alberto
Saelens, Xavier
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv VHHs
Junín
Arenavirus
Neutralizing
topic VHHs
Junín
Arenavirus
Neutralizing
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.
Fil: Linero, Florencia Natalia. Flanders Interuniversity Institute For Biotechnology; Bélgica. University of Ghent; Bélgica
Fil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Christopoulou, Ioanna. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgica
Fil: Hulpiau, Paco. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgica
Fil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Saelens, Xavier. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgica
description The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/94016
Linero, Florencia Natalia; Sepúlveda, Claudia Soledad; Christopoulou, Ioanna; Hulpiau, Paco; Scolaro, Luis Alberto; et al.; Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein; Nature Publishing Group; Scientific Reports; 8; 11451; 12-2018; 1-17
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/94016
identifier_str_mv Linero, Florencia Natalia; Sepúlveda, Claudia Soledad; Christopoulou, Ioanna; Hulpiau, Paco; Scolaro, Luis Alberto; et al.; Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein; Nature Publishing Group; Scientific Reports; 8; 11451; 12-2018; 1-17
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-29508-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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