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Enhanced gene silencing in cells cured of persistent virus infection by RNA interference

Isabelle Pelletier1, Aure Saulnier, Cynthia Brisac

  • 1Institut Pasteur, Unité de Biologie des virus entériques, 25 rue du Dr Roux, 75015 Paris, France.

Journal of Virology
|April 16, 2010
PubMed

Insights

Cells cured of persistent poliovirus infection using RNA interference (RNAi) showed enhanced gene silencing. This suggests the RNAi machinery in cured cells is more efficient than in parental cells.

Area of Science:

  • Molecular Biology
  • Virology
  • Gene Silencing

Background:

  • Persistent viral infections pose challenges for eradication.
  • RNA interference (RNAi) is a natural cellular process for gene silencing.
  • Small interfering RNAs (siRNAs) are key mediators of RNAi.

Purpose of the Study:

  • To investigate changes in RNA interference (RNAi) efficiency in cells cured of poliovirus.
  • To determine if poliovirus curing selects for cells with enhanced gene silencing capabilities.

Main Methods:

  • Comparison of HEp-2-derived cells cured of poliovirus via RNA interference (RNAi) with parental cells.
  • Assessment of poliovirus replication levels in cured and parental cells.
  • Evaluation of small interfering RNA (siRNA)-mediated silencing of green fluorescent protein (GFP) and luciferase in both cell types.

Main Results:

  • Cured cells exhibited lower poliovirus replication, potentially due to enhanced antiviral siRNA activity.
  • Specific siRNAs demonstrated more effective silencing of GFP (from a measles virus vector) and GFP/luciferase (from non-replicating plasmids) in cured cells compared to controls.
  • These findings indicate a selection for cells with improved silencing mechanisms during the curing process.

Conclusions:

  • The RNA interference (RNAi) machinery in poliovirus-cured cells is demonstrably more efficient than in their parental counterparts.
  • The curing process via RNAi actively selects for cells with augmented gene silencing capabilities.

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