Cellular microRNA-miR-548g-3p modulates the replication of dengue virus

J Infect. 2015 Jun;70(6):631-40. doi: 10.1016/j.jinf.2014.12.001. Epub 2014 Dec 11.

Abstract

Objective: It has been well recognized that microRNA plays a role in the host-pathogen interaction network. The significance of microRNA in the regulation of dengue virus (DENV) replication, however, remains unknown. The objective of our study was to determine the biological function of miR-548g-3p in modulating the replication of dengue virus.

Methods: Here we report that employment of a microRNA target search algorithm to analyze the 5' untranslated region (5'UTR) consensus sequences of DENV (DENV serotypes 1-4) led to a discovery that miR-548g-3p directly targets the stem loop A promoter element within the 5'UTR, a region essential for DENV replication. Real-time PCR was used to measure the expression levels of miR-548g-3p under DENV infection. We performed overexpression and inhibition assays to test the role of miR-548g-3p on DENV replication. The protein and mRNA levels of interferon were measured by ELISA and real-time PCR respectively.

Result: We found that overexpression of miR-548g-3p suppressed multiplication of DENV 1, 2, 3 and 4, and that miR-548g-3p was also found to interfere with DENV translation, thereby suppressing the expression of viral proteins.

Conclusion: Our results suggest that miR-548g-3p directly regulates DENV replication and warrant further study to investigate the feasibility of microRNA-based anti-DENV approaches.

Keywords: Dengue virus; Viral replication; miR-548g-3p; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Consensus Sequence
  • Dengue / virology*
  • Dengue Virus / physiology*
  • Gene Expression
  • Genes, Reporter
  • Host-Pathogen Interactions*
  • Humans
  • Interferons / genetics
  • Interferons / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Viral / genetics
  • Vero Cells
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication*

Substances

  • 5' Untranslated Regions
  • MIRN548 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Viral
  • Viral Proteins
  • Interferons