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

Publication date: Available online 1 March 2018
Source:Cell Host & Microbe
Author(s): Enzo Z. Poirier, Bertsy Goic, Lorena Tomé-Poderti, Lionel Frangeul, Jérémy Boussier, Valérie Gausson, Hervé Blanc, Thomas Vallet, Hyelee Loyd, Laura I. Levi, Sophie Lanciano, Chloé Baron, Sarah H. Merkling, Louis Lambrechts, Marie Mirouze, Susan Carpenter, Marco Vignuzzi, Maria-Carla Saleh
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.

Graphical abstract

Teaser

Poirier et al. show that during RNA virus infection of insects, circular viral DNA is produced, regulated by Dicer-2 helicase domain. The main template for viral DNA is defective viral genomes, which appear to be key viral products modulating the host immune response and the establishment of viral persistence.


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