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dc.contributor.author
Hickerson, Brady T.
dc.contributor.author
Daniels Wells, Tracy R.
dc.contributor.author
Payés, Cristian
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Clark, Lars E.
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Candelaria, Pierre V.
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Bailey, Kevin W.
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Sefing, Eric J.
dc.contributor.author
Zink, Samantha
dc.contributor.author
Ziegenbein, James
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Abraham, Jonathan
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Helguera, Gustavo Fernando
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Penichet, Manuel L.
dc.contributor.author
Gowen, Brian
dc.date.available
2022-08-21T19:44:33Z
dc.date.issued
2022-01
dc.identifier.citation
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
dc.identifier.issn
2041-1723
dc.identifier.uri
http://hdl.handle.net/11336/166192
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature
dc.relation
https://ri.conicet.gov.ar/handle/11336/148223
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
MONOCLONAL
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ANTIBODY
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JUNIN VIRUS
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THERAPEUTIC
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HEMORRHAGIC FEVER, AMERICAN
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HOST PATHOGEN INTERACTIONS
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DRUG EFFECTS
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Otras Biotecnologías de la Salud
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Biotecnología de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-08-10T13:38:38Z
dc.journal.volume
13
dc.journal.number
1
dc.journal.pagination
1-13
dc.journal.pais
Alemania
dc.journal.ciudad
Berlín
dc.description.fil
Fil: Hickerson, Brady T.. U.S. Food and Drug Administration. Center for Drug Evaluation and Research; Estados Unidos. State University of Utah; Estados Unidos
dc.description.fil
Fil: Daniels Wells, Tracy R.. University of California at Los Angeles. School of Medicine; Estados Unidos
dc.description.fil
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
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Fil: Clark, Lars E.. Harvard Medical School; Estados Unidos
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Fil: Candelaria, Pierre V.. University of California at Los Angeles. School of Medicine; Estados Unidos
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Fil: Bailey, Kevin W.. State University of Utah; Estados Unidos
dc.description.fil
Fil: Sefing, Eric J.. State University of Utah; Estados Unidos
dc.description.fil
Fil: Zink, Samantha. University of California at Los Angeles; Estados Unidos
dc.description.fil
Fil: Ziegenbein, James. University of California at Los Angeles; Estados Unidos
dc.description.fil
Fil: Abraham, Jonathan. Harvard Medical School; Estados Unidos. Mass General Brigham. Brigham And Women's Hospital; Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Penichet, Manuel L.. University of California at Los Angeles. School of Medicine; Estados Unidos
dc.description.fil
Fil: Gowen, Brian. State University of Utah; Estados Unidos
dc.journal.title
Nature Communications
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-021-27949-3
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41467-021-27949-3
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