RNA-mediated interference and reverse transcription control the persistence of RNA viruses in the insect model Drosophila

Nat Immunol. 2013 Apr;14(4):396-403. doi: 10.1038/ni.2542. Epub 2013 Feb 24.

Abstract

How persistent viral infections are established and maintained is widely debated and remains poorly understood. We found here that the persistence of RNA viruses in Drosophila melanogaster was achieved through the combined action of cellular reverse-transcriptase activity and the RNA-mediated interference (RNAi) pathway. Fragments of diverse RNA viruses were reverse-transcribed early during infection, which resulted in DNA forms embedded in retrotransposon sequences. Those virus-retrotransposon DNA chimeras produced transcripts processed by the RNAi machinery, which in turn inhibited viral replication. Conversely, inhibition of reverse transcription hindered the appearance of chimeric DNA and prevented persistence. Our results identify a cooperative function for retrotransposons and antiviral RNAi in the control of lethal acute infection for the establishment of viral persistence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA Viruses / chemistry
  • DNA Viruses / genetics
  • DNA Viruses / metabolism
  • Disease Models, Animal
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / virology*
  • Female
  • Gene Order
  • Models, Biological
  • Molecular Sequence Data
  • RNA Interference*
  • RNA Virus Infections / virology*
  • RNA Viruses / chemistry
  • RNA Viruses / genetics*
  • RNA Viruses / metabolism
  • RNA, Small Interfering / genetics
  • Retroelements
  • Reverse Transcription*
  • Viral Load
  • Virus Replication / genetics

Substances

  • RNA, Small Interfering
  • Retroelements