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Antiviral RNA interference in mammalian cells.

P V Maillard1, C Ciaudo, A Marchais

  • 1Department of Biology, Swiss Federal Institute of Technology Zurich (ETH-Z), Zurich, Switzerland.

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|October 12, 2013
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Summary

Mammalian cells possess antiviral RNA interference (RNAi) mechanisms. This pathway uses small interfering RNAs (siRNAs) to target and silence viral RNA, demonstrating a conserved defense against viruses.

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Area of Science:

  • Molecular Biology
  • Virology
  • Immunology

Background:

  • Antiviral RNA interference (RNAi) is known in plants and invertebrates.
  • The existence of antiviral RNAi in mammals has not been established.
  • Viruses employ viral suppressors of RNAi (VSRs) to counteract host defenses.

Purpose of the Study:

  • To investigate the presence and function of antiviral RNAi in mammalian cells.
  • To characterize the small RNAs generated during viral infection in mice.
  • To determine if VSRs play a role in viral evasion of mammalian RNAi.

Main Methods:

  • Infection of undifferentiated mouse cells with encephalomyocarditis virus (EMCV) and Nodamura virus (NoV).
  • Analysis of viral RNA and small RNA populations using sequencing.
  • Utilizing Dicer knockout cells and genetically modified viruses.
  • Assessing the impact of VSR ablation on viral load.

Main Results:

  • Accumulation of ~22-nucleotide RNAs with siRNA features derived from viral dsRNA.
  • These small RNAs are incorporated into AGO2 and depend on DICER.
  • Viral suppressor of RNAi (VSR) antagonism of DICER is crucial for viral evasion.
  • Ablating a NoV VSR reduced viral accumulation in infected cells.

Conclusions:

  • Mammalian cells possess an antiviral RNA interference pathway.
  • This pathway utilizes small interfering RNAs (siRNAs) to target viral RNA.
  • Viral suppressors of RNAi are key to viral counter-defense in mammals.