Complex interaction between dengue virus replication and expression of miRNA-133a

BMC Infect Dis. 2016 Jan 27;16:29. doi: 10.1186/s12879-016-1364-y.

Abstract

Background: Dengue virus (DENV) is the most common vector-borne viral infection worldwide with approximately 390 million cases and 25,000 reported deaths each year. MicroRNAs (miRNAs) are small non-coding RNA molecules responsible for the regulation of gene expression by repressing mRNA translation or inducing mRNA degradation. Although miRNAs possess antiviral activity against many mammalian-infecting viruses, their involvement in DENV replication is poorly understood.

Methods: Here, we explored the relationship between DENV and cellular microRNAs using bioinformatics tools. We overexpressed miRNA-133a in Vero cells to test its role in DENV replication and analyzed its expression using RT-qPCR. Furthermore, the expression of polypyrimidine tract binding protein (PTB), a protein involved in DENV replication, was analyzed by western blot. In addition, we profiled miRNA-133a expression in Vero cells challenged with DENV-2, using Taqman miRNA.

Results: Bioinformatic analysis revealed that the 3' untranslated region (3'UTR) of the DENV genome of all four DENV serotypes is targeted by several cellular miRNAs, including miRNA-133a. We found that overexpression of synthetic miRNA-133a suppressed DENV replication. Additionally, we observed that PTB transcription , a miRNA-133a target, is down-regulated during DENV infection. Based in our results we propose that 3'UTR of DENV down-regulates endogenous expression of miRNA-133a in Vero cells during the first hours of infection.

Conclusions: miRNA-133a regulates DENV replication possibly through the modulation of a host factor such as PTB. Further investigations are needed to verify whether miRNA-133a has an anti-DENV effect in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Dengue / virology
  • Dengue Virus / genetics
  • Dengue Virus / physiology*
  • Humans
  • MicroRNAs / biosynthesis*
  • Polypyrimidine Tract-Binding Protein / biosynthesis
  • RNA, Viral / biosynthesis*
  • Vero Cells
  • Virus Replication

Substances

  • MicroRNAs
  • RNA, Viral
  • Polypyrimidine Tract-Binding Protein