Artículo
Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections
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
Fecha de publicación:
01/2022
Editorial:
Nature
Revista:
Nature Communications
ISSN:
2041-1723
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
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
Compartir
Altmétricas
Items relacionados
Mostrando titulos relacionados por título, autor y tema.
-
Ferrero, Sol ; Flores, Maria D.; Short, Connor; Vázquez, Cecilia Alejandra ; Clark, Lars E.; Ziegenbein, James; Zink, Samantha; Fuentes, Daniel; Payés, Cristian ; Batto, María V.; Collazo, Michael; García, Cybele C.; Abraham, Jonathan; Cordo, Sandra Myriam ; Rodriguez, Jose A.; Helguera, Gustavo Fernando (American Society for Microbiology, 2021-09)