miR-146a facilitates replication of dengue virus by dampening interferon induction by targeting TRAF6.

Abstract

OBJECTIVES:

To investigate the role of miR-146a in dengue virus (DENV) replication.

METHODS:

Expression levels of miR-146a were measured by real-time PCR and Northern blot. Role of miR-146a was tested by overexpression and inhibition assays. Real-time PCR and 50% tissue culture infective dose (TCID50) assays were used to detect RNA levels and extracellular yields of DENV respectively. Interferon (IFN) levels induced by DENV infection were measured by real-time PCR and ELISA respectively. IFN-β neutralization and RNAi were used to test the involvement of IFN-β in the effects of miR-146a. TNFR-associated factor 6 (TRAF6) level was measured by Western-blot.

RESULTS:

miR-146a expression was significantly increased in primary human monocytes and THP-1 cells upon DENV infection. Overexpression of miR-146a increased DENV2 replication, while inhibition of miR-146a decreased the viral replication. miR-146a impaired the IFN production and the DENV2 replication suppressed by miR-146a inhibition was partially restored by neutralization of IFN-β or depletion of interferon receptor (IFNAR) 1 or 2. Furthermore, miR-146a targets TRAF6 and overexpression of TRAF6 reversed the effects of miR-146a on IFN-β induction and viral replication.

CONCLUSIONS:

DENV infection significantly induced the expression of miR-146a, which facilitated viral replication by targeting TRAF6 and dampening IFN-β production.

• Authors: Siyu Wu, Li He, Yuye Li, Tinglong Wang, Lianqiang Feng, Lifang Jiang, Ping Zhang, Xi Huang
• Journal: The Journal of infection (J Infect) Vol. 67 Issue 4 Pg. 329-41 (Oct 2013) ISSN: 1532-2742 [Electronic] England
• PMID: 23685241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Chemical References

• MIRN146 microRNA, human
• MicroRNAs
• TNF Receptor-Associated Factor 6
• Interferon-beta

Topics

• Blotting, Northern
• Blotting, Western
• Cells, Cultured
• Dengue Virus (immunology, physiology)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Profiling
• Humans
• Interferon-beta (biosynthesis, immunology)
• MicroRNAs (genetics, metabolism)
• Monocytes (immunology, virology)
• Real-Time Polymerase Chain Reaction
• TNF Receptor-Associated Factor 6 (antagonists & inhibitors, metabolism)
• Virus Replication