The cytokine DIEDEL and a viral homologue suppress deleterious IMD-dependent gene expression in drosophila

Viral infection in Drosophila triggers inducible gene expression, but the function of many of these genes and the biological significance of their induction remain poorly understood. Here, we report the functional characterization of the gene Diedel, which is strongly induced following some viral infections and encodes a 12kDa circulating protein. Diedel mutant flies have reduced viability and succumb rapidly to infection with Sindbis virus. This phenotype is associated with deregulated expression of IMD target genes and is rescued by mutations in the genes imd or IKKg, indicating that Diedel functions as an immunosuppressor cytokine targeting the IMD pathway. Homologues of Diedel are found in the genome of several DNA viruses, providing the first example of virokines in insects. Our results reveal that, besides RNA interference and apoptosis, an NF-kB pathway of inducible defense exerts evolutionary pressure on insect viruses. For each experimental condition (non infected and SINV infected), two biologically independent samples composed of 45 males of w1118 or Diedelcfm null mutant flies were used. Infection has been performed by injecting viral stocks prepared in Tris solution. Flies were then incubated for days at 29°C.