title: Complex interaction between dengue virus replication and expression of miRNA-133a.
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.
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellin, Colombia.
authors.forename: Jorge Andrés
authors.initials: JA
authors.lastname: Castillo
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellin, Colombia.
authors.forename: Juan Camilo
authors.initials: JC
authors.lastname: Castrillón
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellin, Colombia.|Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Mayra
authors.initials: M
authors.lastname: Diosa-Toro
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellin, Colombia.
authors.forename: Juan Guillermo
authors.initials: JG
authors.lastname: Betancur
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellin, Colombia.|St Laurent Institute, 317 New Boston St, Woburn, MA, 01801, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: St Laurent
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: Smit
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellin, Colombia. Silvio.urcuqui@udea.edu.co.
authors.forename: Silvio
authors.initials: S
authors.lastname: Urcuqui-Inchima
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003715:Dengue / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D038941:Polypyrimidine Tract-Binding Protein / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis*; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral; D038941:Polypyrimidine Tract-Binding Protein
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