Invading viral DNA triggers dsRNA synthesis by RNA polymerase II to activate antiviral RNA interference in Drosophila

Isaque J.S. de Faria, Eric R.G.R. Aguiar, Roenick P. Olmo, Juliana Alves da Silva, Laurent Daeffler, Richard W. Carthew, Jean Luc Imler, João T. Marques*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

dsRNA sensing triggers antiviral responses against RNA and DNA viruses in diverse eukaryotes. In Drosophila, Invertebrate iridescent virus 6 (IIV-6), a large DNA virus, triggers production of small interfering RNAs (siRNAs) by the dsRNA sensor Dicer-2. Here, we show that host RNA polymerase II (RNAPII) bidirectionally transcribes specific AT-rich regions of the IIV-6 DNA genome to generate dsRNA. Both replicative and naked IIV-6 genomes trigger production of dsRNA in Drosophila cells, implying direct sensing of invading DNA. Loquacious-PD, a Dicer-2 co-factor essential for the biogenesis of endogenous siRNAs, is dispensable for processing of IIV-6-derived dsRNAs, which suggests that they are distinct. Consistent with this finding, inhibition of the RNAPII co-factor P-TEFb affects the synthesis of endogenous, but not virus-derived, dsRNA. Altogether, our results suggest that a non-canonical RNAPII complex recognizes invading viral DNA to synthesize virus-derived dsRNA, which activates the antiviral siRNA pathway in Drosophila.

Original languageEnglish (US)
Article number110976
JournalCell reports
Volume39
Issue number12
DOIs
StatePublished - Jun 21 2022

Keywords

  • CP: Immunology
  • DNA sensing
  • antiviral RNAi
  • dsRNA
  • invertebrate immunity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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