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J Infect. 2013 Oct;67(4):329-41. doi: 10.1016/j.jinf.2013.05.003. Epub 2013 May 16.

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

Author information

1
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

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.

KEYWORDS:

Dengue virus; Interferon; MicroRNA; Replication; TRAF6

PMID:
23685241
DOI:
10.1016/j.jinf.2013.05.003
[Indexed for MEDLINE]

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