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Interferon modulation of cellular microRNAs as an antiviral mechanism

Academic Article
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Overview

authors

  • Pedersen, I. M.
  • Cheng, G.
  • Wieland, Stefan
  • Volinia, S.
  • Croce, C. M.
  • Chisari, Francis
  • David, M.

publication date

  • 2007

journal

  • Nature  Journal

abstract

  • RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in the defence against viral infection in mammalian organisms has thus far remained elusive. Here we show that interferon beta (IFNbeta) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFNbeta-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFNbeta-induced miRNAs reproduces the antiviral effects of IFNbeta on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFNbeta against HCV. In addition, we demonstrate that IFNbeta treatment leads to a significant reduction in the expression of the liver-specific miR-122, an miRNA that has been previously shown to be essential for HCV replication. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.

subject areas

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cells, Cultured
  • Genome, Viral
  • Hepacivirus
  • Hepatocytes
  • Humans
  • Immunity, Innate
  • Interferon-beta
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs
  • RNA Interference
  • RNA, Viral
  • Virus Replication
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Identity

PubMed Central ID

  • PMC2748825

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature06205

PubMed ID

  • 17943132
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Additional Document Info

start page

  • 919

end page

  • 922

volume

  • 449

issue

  • 7164

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