DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection.
PLoS Pathog
; 14(7): e1007125, 2018 07.
Article
in En
| MEDLINE
| ID: mdl-30001425
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
Arenaviridae Infections
/
DEAD-box RNA Helicases
/
Host-Pathogen Interactions
/
Immune Evasion
Limits:
Humans
Language:
En
Journal:
PLoS Pathog
Year:
2018
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos