Over the past few years, insect immunologists working with Drosophila, exploiting its unparalleled power as a model system (forward genetic screening in adult flies, genome-wide RNAi screening of Drosophila cell lines, and sequenced genome of 12 Drosophila genomes, providing a unique opportunity for comparative genomics), have made significant progress towards deciphering many aspects of antiviral immune defence mechanisms in insects. Even though we are still far from having a complete picture of the mechanisms of resistance to viral infections in flies, it is clear at this stage that flies can defend themselves against virus infections, and that the mechanisms involved are mostly different from those triggering the humoral response activated by bacterial and fungal infections. As has already been appreciated in previous studies on bacterial and fungal infections, the mechanisms involved are evolutionarily conserved, at least in part. Of note, it appears that there may be more than one type of antiviral immune response, as exemplified by the importance of Dicer-2 to control infection by DCV, FHV, and SINV, but not DXV; the induction of Tot genes by FHV but not by DCV; and the role of dSUR in the resistance to FHV, but not DCV infection. It will take some time to fully appreciate the complexity of antiviral immunity in Drosophila. In addition, our data with KATP channels indicate that, both in flies and mammals, antiviral immunity is only one of the parameters that affect the outcome of the pathogenesis associated with viral infection. Drosophila provides an ideal system to address experimentally the complex issue of homeostasis in virus-infected animals, and to provide an integrative view, at the organism level, of the complex interaction between viruses and their hosts. One can hope that this understanding will lead to new concepts that will be helpful to unravel the genetic mechanisms of antiviral resistance in more complex organisms (i.e. mammals). These studies are also likely to be of relevance for the understanding of the interactions between vector insects and arboviruses, a major challenge for the years to come.
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