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

Enzo Poirier (1, 2, 3) , Bertsy Goic (1) , Lorena Tomé-Poderti (1) , Lionel Frangeul (1) , Jeremy Boussier (4) , Valérie Gausson (1) , Hervé Blanc (1, 2) , Thomas Vallet (2) , Hyelee Loyd (5) , Laura Levi (2) , Sophie Lanciano (6) , Chloé Baron (1) , Sarah Merkling (7) , Louis Lambrechts (7) , Marie Mirouze (6) , Susan Carpenter (5) , Marco Vignuzzi (2) , Maria-Carla P Saleh (1)

1 Virus et Interférence ARN - Viruses and RNA Interference
2 Populations virales et Pathogenèse - Viral Populations and Pathogenesis
3 Cellule Pasteur
4 Immunobiologie des Cellules dendritiques
5 ISU - Iowa State University
6 UMR DIADE - Diversité, adaptation, développement des plantes
7 IVI - Interactions Virus-Insectes - Insect-Virus Interactions

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.

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

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire; Biologie moléculaire; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Immunologie; Virologie

Enzo Poirier, Bertsy Goic, Lorena Tomé-Poderti, Lionel Frangeul, Jeremy Boussier, et al.. Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects. Cell Host and Microbe, 2018, 23 (3), pp.353-365.e8. ⟨10.1016/j.chom.2018.02.001⟩. ⟨pasteur-01952531⟩