Artículo
DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
Loureiro, Maria Eugenia
; Zorzetto Fernandes, Andre Luiz; Radoshitzky, Sheli; Chi, Xiaoli; Dallari, Simone; Marooki, Nuha; Lèger, Psylvia; Foscaldi, Sabrina Andrea
; Harjono, Vince; Sharma, Sonia; Zid, Brian M.; Lopez, Nora Mabel
; de la Torre, Juan Carlos; Bavari, Sina; Zuniga, Elina Isabel
Fecha de publicación:
07/2018
Editorial:
Public Library of Science
Revista:
Plos Pathogens
ISSN:
1553-7366
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication associated with both a previously un-recognized DDX3 inhibitory role in type I interferon production in arenavirus infected cells and a positive DDX3 effect on arenavirus RNA synthesis that was dependent on its ATPase and Helicase activities. Our results uncover novel mechanisms used by arenaviruses to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.
Palabras clave:
ARENAVIRUS
,
DDX3
,
REPLICATION
,
INTERFERON
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos (CEVHAN)
Articulos de CENTRO DE VIROLOGIA HUMANA Y ANIMAL
Articulos de CENTRO DE VIROLOGIA HUMANA Y ANIMAL
Articulos(ICT - MILSTEIN)
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Citación
Loureiro, Maria Eugenia; Zorzetto Fernandes, Andre Luiz; Radoshitzky, Sheli; Chi, Xiaoli; Dallari, Simone; et al.; DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-28; e1007125
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