miR-146a Inhibits dengue-virus-induced autophagy by targeting TRAF6.
Arch Virol
; 162(12): 3645-3659, 2017 Dec.
Article
in En
| MEDLINE
| ID: mdl-28825144
ABSTRACT
During dengue virus (DENV) infection, the virus manipulates different cellular pathways to assure productive replication, including autophagy. However, it remains unclear how this autophagic process is regulated. Here, we have demonstrated a novel role for the microRNA miR-146a in negatively regulating the cellular autophagic pathway in DENV-infected A549 cells and THP-1 cells. Overexpression of miR-146a significantly blocked DENV2-induced autophagy, and LNA-mediated inhibition of miR-146a counteracted these effects. Moreover, co-overexpression of TRAF6, a target of miR-146a, significantly reversed the inhibitory effect of miR-146a on autophagy. Notably, treatment with recombinant IFN-ß fully restored the autophagic activity in TRAF6-silenced cells. Furthermore, our data showed that, in DENV2-infected A549 cells, autophagy promoted a pro-inflammatory response to significantly increase TNF-α and IL-6 production. Taken together, our results define a novel role for miR-146a as a negative regulator of DENV-induced autophagy and identify TRAF6 as a key target of this microRNA in modulating the DENV-autophagy interaction.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Dengue Virus
/
MicroRNAs
/
TNF Receptor-Associated Factor 6
/
Host-Pathogen Interactions
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Arch Virol
Year:
2017
Document type:
Article
Affiliation country:
China