Innate and intrinsic antiviral immunity in Drosophila

Abstract

The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.

Keywords: Argonaute 2; Dicer-2; IMD pathway; Jak/STAT pathway; NF-κB.

Fig. 1

The siRNA pathway in Drosophila. The three core proteins of the RNAi machinery (Dicer-2, R2D2 and AGO2) associate with cofactors to sense RNAs and form the RNA-induced silencing complex (RISC). The siRNA pathway can be activated by the delivery of exogenous dsRNA in the cytosol or by viruses, but also by the transcription in the nucleus of natural antisense transcripts (NATs) or structured RNA. Virus-encoded suppressor molecules (in red triangles) inhibit the pathway at different steps (see the text for details)

Fig. 2

Induced antiviral responses in Drosophila. Examples of signalling pathways activated by viruses in flies are illustrated. Viral suppressors are indicated by red triangles. See the text for details

Fig. 3

Adaptation of Drosophila to DCV highlights the importance of restriction factors. a Flies grown for 20 generations under DCV infection show increased survival upon infection with the virus compared to controls. b Comparison of allele frequencies between control and virus-selected populations at generation 20 identified by genome-wide sequencing. The arrowheads indicate the localization of causal polymorphisms on the left arm of chromosome 3 and on chromosome X. CMH Cochran–Mantel–Haenszel test. c Schematic representation of the Pst and Ubc-E2H genes, with coding regions in green, and the location of polymorphism indicated in the exon 7 of Pst and in the intron of Ubc-E2H. a and b were redrawn and adapted from [140]