Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells

Virus Res. 2015 Jan 22:196:105-12. doi: 10.1016/j.virusres.2014.11.010. Epub 2014 Nov 20.

Abstract

MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells.

Keywords: BACH1; Dengue virus; Let-7c; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Dengue Virus / genetics*
  • Dengue Virus / metabolism
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Expression*
  • Genome, Viral
  • Heme Oxygenase-1 / genetics
  • Host-Pathogen Interactions / genetics
  • Humans
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Viral
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Reproducibility of Results
  • Time Factors
  • Transfection
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / genetics*

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Fanconi Anemia Complementation Group Proteins
  • Lin28A protein, human
  • MicroRNAs
  • RNA, Viral
  • RNA-Binding Proteins
  • Viral Nonstructural Proteins
  • mirnlet7 microRNA, human
  • Heme Oxygenase-1