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Cell Host Microbe. 2018 Mar 14;23(3):353-365.e8. doi: 10.1016/j.chom.2018.02.001. Epub 2018 Mar 1.

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

Author information

1
Institut Pasteur, Viruses and RNA Interference, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France; Institut Pasteur, Viral Populations and Pathogenesis, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France.
2
Institut Pasteur, Viruses and RNA Interference, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France.
3
Institut Pasteur, Immunobiology of Dendritic Cells, Institut National de la Santé et de la Recherche Médicale, U1223, 75015 Paris, France.
4
Institut Pasteur, Viruses and RNA Interference, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France; Institut Pasteur, Viral Populations and Pathogenesis, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France.
5
Institut Pasteur, Viral Populations and Pathogenesis, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France.
6
Department of Animal Science, Iowa State University, Ames, IA 50010, USA.
7
Institut de Recherche pour le Développement, DIADE, Université de Montpellier, Université de Perpignan, LGDP, 66860 Perpignan, France.
8
Institut Pasteur, Insect-Virus Interactions, Centre National de la Recherche Scientifique URA 3012, 75015 Paris, France.
9
Institut Pasteur, Viral Populations and Pathogenesis, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France. Electronic address: marco.vignuzzi@pasteur.fr.
10
Institut Pasteur, Viruses and RNA Interference, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France. Electronic address: carla.saleh@pasteur.fr.

Abstract

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.

KEYWORDS:

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

Comment in

PMID:
29503180
PMCID:
PMC5857290
DOI:
10.1016/j.chom.2018.02.001
[Indexed for MEDLINE]
Free PMC Article

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