Immune priming and clearance of orally acquired RNA viruses in Drosophila

Nat Microbiol. 2018 Dec;3(12):1394-1403. doi: 10.1038/s41564-018-0265-9. Epub 2018 Oct 29.


Immune responses in insects are differentially triggered depending on the infection route used by the pathogen. In most studies involving Drosophila melanogaster and viruses, infection is done by injection, while oral infection, which is probably the most common route of viral entry in nature, remains unexplored. Here, we orally infected adults and larvae from wild-type and RNA interference (RNAi) mutant flies with different RNA viruses. We found that, in contrast with what is observed following virus injection, oral infections initiated at larval or adult stages are cleared in adult flies. Virus elimination occurred despite a larger infectious dose than for injected flies and evidence of viral replication. RNAi mutant flies suffered greater mortality relative to wild-type flies following oral infection, but they also eliminated the virus, implying that RNAi is not essential for viral clearance and that other immune mechanisms act during oral infections. We further showed that information of infection by RNA viruses acquired orally leaves a trace under a DNA form, which confers protection against future reinfection by the same virus. Together, this work presents evidence of clearance and immune priming for RNA viruses in insects and challenges the current view of antiviral immunity in insects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology
  • Argonaute Proteins / genetics
  • Argonaute Proteins / immunology
  • DNA, Viral / immunology
  • Disease Models, Animal
  • Drosophila Proteins / genetics
  • Drosophila Proteins / immunology
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / virology*
  • Female
  • Larva / virology
  • Male
  • RNA Helicases / genetics
  • RNA Helicases / immunology
  • RNA Interference / immunology*
  • RNA Virus Infections / immunology*
  • RNA Viruses / immunology*
  • RNA Viruses / pathogenicity*
  • Ribonuclease III / genetics
  • Ribonuclease III / immunology
  • Survival Analysis
  • Virus Replication


  • AGO2 protein, Drosophila
  • Antiviral Agents
  • Argonaute Proteins
  • DNA, Viral
  • Drosophila Proteins
  • DCR-2 protein, Drosophila
  • Ribonuclease III
  • RNA Helicases