MicroRNA-30e* suppresses dengue virus replication by promoting NF-κB-dependent IFN production

PLoS Negl Trop Dis. 2014 Aug 14;8(8):e3088. doi: 10.1371/journal.pntd.0003088. eCollection 2014 Aug.

Abstract

MicroRNAs have been shown to contribute to a repertoire of host-pathogen interactions during viral infection. Our previous study demonstrated that microRNA-30e* (miR-30e*) directly targeted the IκBα 3'-UTR and disrupted the NF-κB/IκBα negative feedback loop, leading to hyperactivation of NF-κB. This current study investigated the possible role of miR-30e* in the regulation of innate immunity associated with dengue virus (DENV) infection. We found that DENV infection could induce miR-30e* expression in DENV-permissive cells, and such an overexpression of miR-30e* upregulated IFN-β and the downstream IFN-stimulated genes (ISGs) such as OAS1, MxA and IFITM1, and suppressed DENV replication. Furthermore, suppression of IκBα mediates the enhancing effect of miR-30e* on IFN-β-induced antiviral response. Collectively, our findings suggest a modulatory role of miR-30e* in DENV induced IFN-β signaling via the NF-κB-dependent pathway. Further investigation is needed to evaluate whether miR-30e* has an anti-DENV effect in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes / cytology
  • Animals
  • Cell Line
  • Dengue Virus* / drug effects
  • Dengue Virus* / immunology
  • Humans
  • Interferons / metabolism*
  • MicroRNAs / pharmacology*
  • NF-kappa B / metabolism*
  • Virus Replication / drug effects*

Substances

  • MicroRNAs
  • NF-kappa B
  • Interferons

Grants and funding

This work was supported by the National Mega Project on Major Infectious Disease Prevention (2012ZX10004-213); the Key (Key grant) Project of Chinese Ministry of Education (NO. 311030); Natural Science Foundation of China (81330058, 81272417, 81102370); Guangdong Recruitment Program of Creative Research Groups (No. 2009010058); National Science and Technique Major Project (201305017, 2012ZX09102101-017); and The Key Science and Technique Research Project of Guangzhou City (12B292060029). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.