Induced antiviral innate immunity in Drosophila

Abstract

Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals.

Figure 1. Induced antiviral responses in Drosophila

Induction of specific antiviral pathways in Drosophila melanogaster triggered by different viruses. (a) Apoptosis is induced during the infection by the DNA virus AcMNPV. (b) Infection by VSV and RVFV, two negative sense single-stranded (ss) RNA viruses, trigger antiviral autophagy program. The inhibition of PI3K by Toll-7 and the contribution of Ref(2)P remain poorly characterized. (c) Induction of antiviral effectors during the infection of the positive ssRNA DCV is mediated by DExD/H box helicase Dicer-2, which senses dsRNA produced by the viral RNA-dependent RNA polymerase (vRdRP). The triggers are indicated in red, the sensors are boxed and the viral components are in green. See the text for details.

Figure 2. Inducible transcriptional responses to viral infection in Drosophila

(a) Venn diagram of genes induced during an infection by SINV in adult flies [16], in S2 cells [18] and adult flies expressing a SINV replicon [15]. (b) Venn diagram of genes induced during an infection by FHV in adult flies [16], in S2 cells and S2 cells expressing a RNA1 FHV replicon [17]. (c) Venn diagram of genes induced during an infection by SINV, FHV and DCV in wild type Oregon-R adult flies [16]. (d) Survival of wild type flies Oregon-R following infection by the indicated viruses. For panels a-c, published data were compared using GeneVenn (http://genevenn.sourceforge.net/). The total of genes induced in each condition is indicated in parenthesis. See supplementary Table 1 for details.