Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections

Autores
Hickerson, Brady T.; Daniels Wells, Tracy R.; Payés, Cristian; Clark, Lars E.; Candelaria, Pierre V.; Bailey, Kevin W.; Sefing, Eric J.; Zink, Samantha; Ziegenbein, James; Abraham, Jonathan; Helguera, Gustavo Fernando; Penichet, Manuel L.; Gowen, Brian
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology.
Fil: Hickerson, Brady T.. U.S. Food and Drug Administration. Center for Drug Evaluation and Research; Estados Unidos. State University of Utah; Estados Unidos
Fil: Daniels Wells, Tracy R.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Clark, Lars E.. Harvard Medical School; Estados Unidos
Fil: Candelaria, Pierre V.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Bailey, Kevin W.. State University of Utah; Estados Unidos
Fil: Sefing, Eric J.. State University of Utah; Estados Unidos
Fil: Zink, Samantha. University of California at Los Angeles; Estados Unidos
Fil: Ziegenbein, James. University of California at Los Angeles; Estados Unidos
Fil: Abraham, Jonathan. Harvard Medical School; Estados Unidos. Mass General Brigham. Brigham And Women's Hospital; Estados Unidos
Fil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of California at Los Angeles; Estados Unidos
Fil: Penichet, Manuel L.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Gowen, Brian. State University of Utah; Estados Unidos
Materia
MONOCLONAL
ANTIBODY
JUNIN VIRUS
THERAPEUTIC
HEMORRHAGIC FEVER, AMERICAN
HOST PATHOGEN INTERACTIONS
DRUG EFFECTS
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:11336/166192
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/166192
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infectionsHickerson, Brady T.Daniels Wells, Tracy R.Payés, CristianClark, Lars E.Candelaria, Pierre V.Bailey, Kevin W.Sefing, Eric J.Zink, SamanthaZiegenbein, JamesAbraham, JonathanHelguera, Gustavo FernandoPenichet, Manuel L.Gowen, BrianMONOCLONALANTIBODYJUNIN VIRUSTHERAPEUTICHEMORRHAGIC FEVER, AMERICANHOST PATHOGEN INTERACTIONSDRUG EFFECTShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology.Fil: Hickerson, Brady T.. U.S. Food and Drug Administration. Center for Drug Evaluation and Research; Estados Unidos. State University of Utah; Estados UnidosFil: Daniels Wells, Tracy R.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Clark, Lars E.. Harvard Medical School; Estados UnidosFil: Candelaria, Pierre V.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Bailey, Kevin W.. State University of Utah; Estados UnidosFil: Sefing, Eric J.. State University of Utah; Estados UnidosFil: Zink, Samantha. University of California at Los Angeles; Estados UnidosFil: Ziegenbein, James. University of California at Los Angeles; Estados UnidosFil: Abraham, Jonathan. Harvard Medical School; Estados Unidos. Mass General Brigham. Brigham And Women's Hospital; Estados UnidosFil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of California at Los Angeles; Estados UnidosFil: Penichet, Manuel L.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Gowen, Brian. State University of Utah; Estados UnidosNature2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/166192Hickerson, Brady T.; Daniels Wells, Tracy R.; Payés, Cristian; Clark, Lars E.; Candelaria, Pierre V.; et al.; Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections; Nature; Nature Communications; 13; 1; 1-2022; 1-132041-1723CONICET DigitalCONICETenghttps://ri.conicet.gov.ar/handle/11336/148223info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-021-27949-3info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-27949-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:06Zoai:ri.conicet.gov.ar:11336/166192instacron: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:34982025-09-03 10:07:07.222CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
title Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
spellingShingle Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
Hickerson, Brady T.
MONOCLONAL
ANTIBODY
JUNIN VIRUS
THERAPEUTIC
HEMORRHAGIC FEVER, AMERICAN
HOST PATHOGEN INTERACTIONS
DRUG EFFECTS
title_short Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
title_full Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
title_fullStr Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
title_full_unstemmed Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
title_sort Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
dc.creator.none.fl_str_mv Hickerson, Brady T.
Daniels Wells, Tracy R.
Payés, Cristian
Clark, Lars E.
Candelaria, Pierre V.
Bailey, Kevin W.
Sefing, Eric J.
Zink, Samantha
Ziegenbein, James
Abraham, Jonathan
Helguera, Gustavo Fernando
Penichet, Manuel L.
Gowen, Brian
author Hickerson, Brady T.
author_facet Hickerson, Brady T.
Daniels Wells, Tracy R.
Payés, Cristian
Clark, Lars E.
Candelaria, Pierre V.
Bailey, Kevin W.
Sefing, Eric J.
Zink, Samantha
Ziegenbein, James
Abraham, Jonathan
Helguera, Gustavo Fernando
Penichet, Manuel L.
Gowen, Brian
author_role author
author2 Daniels Wells, Tracy R.
Payés, Cristian
Clark, Lars E.
Candelaria, Pierre V.
Bailey, Kevin W.
Sefing, Eric J.
Zink, Samantha
Ziegenbein, James
Abraham, Jonathan
Helguera, Gustavo Fernando
Penichet, Manuel L.
Gowen, Brian
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MONOCLONAL
ANTIBODY
JUNIN VIRUS
THERAPEUTIC
HEMORRHAGIC FEVER, AMERICAN
HOST PATHOGEN INTERACTIONS
DRUG EFFECTS
topic MONOCLONAL
ANTIBODY
JUNIN VIRUS
THERAPEUTIC
HEMORRHAGIC FEVER, AMERICAN
HOST PATHOGEN INTERACTIONS
DRUG EFFECTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology.
Fil: Hickerson, Brady T.. U.S. Food and Drug Administration. Center for Drug Evaluation and Research; Estados Unidos. State University of Utah; Estados Unidos
Fil: Daniels Wells, Tracy R.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Clark, Lars E.. Harvard Medical School; Estados Unidos
Fil: Candelaria, Pierre V.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Bailey, Kevin W.. State University of Utah; Estados Unidos
Fil: Sefing, Eric J.. State University of Utah; Estados Unidos
Fil: Zink, Samantha. University of California at Los Angeles; Estados Unidos
Fil: Ziegenbein, James. University of California at Los Angeles; Estados Unidos
Fil: Abraham, Jonathan. Harvard Medical School; Estados Unidos. Mass General Brigham. Brigham And Women's Hospital; Estados Unidos
Fil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of California at Los Angeles; Estados Unidos
Fil: Penichet, Manuel L.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Gowen, Brian. State University of Utah; Estados Unidos
description Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
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/11336/166192
Hickerson, Brady T.; Daniels Wells, Tracy R.; Payés, Cristian; Clark, Lars E.; Candelaria, Pierre V.; et al.; Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections; Nature; Nature Communications; 13; 1; 1-2022; 1-13
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/166192
identifier_str_mv Hickerson, Brady T.; Daniels Wells, Tracy R.; Payés, Cristian; Clark, Lars E.; Candelaria, Pierre V.; et al.; Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections; Nature; Nature Communications; 13; 1; 1-2022; 1-13
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://ri.conicet.gov.ar/handle/11336/148223
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-021-27949-3
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-27949-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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
publisher.none.fl_str_mv Nature
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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score 13.13397

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