Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects

Cell Host Microbe. 2018 Mar 14;23(3):353-365.e8. doi: 10.1016/j.chom.2018.02.001. Epub 2018 Mar 1.


The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis. Accordingly, DVGs promote the amplification of vDNA-mediated antiviral RNAi responses in infected Drosophila. Furthermore, vDNA synthesis is regulated by the DExD/H helicase domain of Dicer-2 in a mechanism distinct from its role in siRNA generation. We suggest that, analogous to mammalian RIG-I-like receptors, Dicer-2 functions like a pattern recognition receptor for DVGs to modulate antiviral immunity in insects.

Keywords: Dicer-2; RNA virus; RNAi; arbovirus; circular viral DNA; defective viral genomes; insect; persistence.

MeSH terms

  • Animals
  • Antiviral Agents / immunology*
  • Arboviruses / immunology
  • Arboviruses / pathogenicity
  • Culicidae / immunology
  • DEAD-box RNA Helicases / metabolism
  • DNA, Viral / metabolism*
  • Drosophila / immunology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Genes, Viral / genetics
  • Genome, Viral
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Point Mutation
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Interference / immunology
  • RNA Virus Infections
  • RNA Viruses / genetics
  • RNA Viruses / immunology*
  • RNA Viruses / pathogenicity
  • RNA, Small Interfering / genetics
  • RNA, Viral / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*
  • Viral Load
  • Virus Replication


  • Antiviral Agents
  • DNA, Viral
  • Drosophila Proteins
  • RNA, Small Interfering
  • RNA, Viral
  • DCR-2 protein, Drosophila
  • Ribonuclease III
  • DEAD-box RNA Helicases
  • RNA Helicases