Modulation of GB virus B RNA abundance by microRNA-122: dependence on and escape from microRNA-122 restriction

J Virol. 2013 Jul;87(13):7338-47. doi: 10.1128/JVI.00378-13. Epub 2013 Apr 24.


Hepatitis C virus (HCV) RNA forms an unusual interaction with human microRNA-122 (miR-122) that promotes viral RNA accumulation in cultured human liver cells and in the livers of infected chimpanzees. GB virus B (GBV-B) is a hepatotropic virus and close relative of HCV. Thus, GBV-B has been used as a surrogate system to study HCV amplification in cultured cells and in infected tamarins. It was discovered that the 5'-terminal sequences of GBV-B RNA, like HCV RNA, forms an Argonaute 2-mediated complex with two miR-122 molecules that are essential for accumulation of GBV-B subgenomic replicon RNA. However, sequences in miR-122 that anneal to each viral RNA genome were different, suggesting distinct overall structural features in HCV:miR-122 and GBV-B:miR-122 complexes. Surprisingly, a deletion that removed both miR-122 binding sites from the subgenomic GBV-B RNAs rendered viral RNA amplification independent from miR-122 and Argonaute 2. This finding suggests that structural features at the end of the viral genome dictate whether miR-122 is required to aid in maintaining viral RNA abundance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / metabolism*
  • Blotting, Northern
  • Cell Line, Tumor
  • DNA Primers / genetics
  • GB virus B / genetics*
  • GB virus B / metabolism
  • Gene Expression Regulation, Viral / physiology*
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Humans
  • Luciferases
  • MicroRNAs / metabolism*
  • Mutagenesis
  • Plasmids / genetics
  • RNA, Viral / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Replicon / genetics
  • Transfection


  • AGO2 protein, human
  • Argonaute Proteins
  • DNA Primers
  • MIRN122 microRNA, human
  • MicroRNAs
  • RNA, Viral
  • Luciferases