Mechanism of induction and suppression of antiviral immunity directed by virus-derived small RNAs in Drosophila

Cell Host Microbe. 2008 Oct 16;4(4):387-97. doi: 10.1016/j.chom.2008.09.001.


The small RNA-directed viral immunity pathway in plants and invertebrates begins with the production by Dicer nuclease of virus-derived siRNAs (viRNAs), which guide specific antiviral silencing by Argonaute protein in an RNA-induced silencing complex (RISC). Molecular identity of the viral RNA precursor of viRNAs remains a matter of debate. Using Flock house virus (FHV) infection of Drosophila as a model, we show that replication of FHV positive-strand RNA genome produces an approximately 400 bp dsRNA from its 5' terminus that serves as the major Dicer-2 substrate. ViRNAs thus generated are loaded in Argonaute-2 and methylated at their 3' ends. Notably, FHV-encoded RNAi suppressor B2 protein interacts with both viral dsRNA and RNA replicase and inhibits production of the 5'-terminal viRNAs. Our findings, therefore, provide a model in which small RNA-directed viral immunity is induced during the initiation of viral progeny (+)RNA synthesis and suppressed by B2 inside the viral RNA replication complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Argonaute Proteins
  • Drosophila / immunology*
  • Drosophila / virology*
  • Drosophila Proteins / metabolism
  • Gene Silencing*
  • Methylation
  • Models, Biological
  • Nodaviridae / immunology*
  • RNA Helicases / metabolism
  • RNA Processing, Post-Transcriptional
  • RNA Virus Infections / immunology*
  • RNA, Double-Stranded / immunology
  • RNA, Double-Stranded / metabolism
  • RNA, Small Interfering / immunology*
  • RNA, Small Interfering / metabolism
  • RNA, Viral / immunology
  • RNA, Viral / metabolism
  • RNA-Induced Silencing Complex / metabolism
  • Ribonuclease III


  • AGO2 protein, Drosophila
  • Argonaute Proteins
  • Drosophila Proteins
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • RNA, Viral
  • RNA-Induced Silencing Complex
  • DCR-2 protein, Drosophila
  • Ribonuclease III
  • RNA Helicases