Abstract
The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-κB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.
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Acknowledgements
We thank S. Ozkan for help with transgenesis; M.-C. Lacombe for assistance with real-time quantitative RT-PCR analysis; J. Mutterer and D. Zachary for help with the confocal microscopy; E. Santiago for technical support; D. Ferrandon and J. Royet for discussions and critical reading of the manuscript; N. Perrimon, J. Castelli-Gair Hombria and J. Darnell for providing fly stocks; and A. Schneemann for the FHV stock and discussions. Supported by Centre National de la Recherche Scientifique and Ministère de la Recherche et de la Technologie (Actions Concertées Incitatives Physiologie Intégrative and Microbiologie, and Programme puces Affymetrix); Institut Universitaire de France; Ligue contre le Cancer (E.J.); Centre National de la Recherche Scientifique (D.G.A.); and Ministère de la Recherche du Grand-Duché de Luxembourg (C.D.).
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Supplementary information
Supplementary Fig. 1
Susceptibility of wild-type flies to DCV infection. (PDF 98 kb)
Supplementary Fig. 2
DCV infection upregulates expression of genes across a broad range of functional categories. (PDF 56 kb)
Supplementary Fig. 3
Characterization of the vir-1 transcript and promoter. (PDF 112 kb)
Supplementary Fig. 4
Constitutive activity of the vir-1 promoter in S2 cells is dependent on the presence of a consensus STAT92E binding site at position -342. (PDF 91 kb)
Supplementary Fig. 5
Susceptibility of wild-type and hopM38/msvl mutant flies to infection with different doses of DCV. (PDF 93 kb)
Supplementary Table 1
Genes up-regulated at least two-fold or induced by DCV infection. (PDF 91 kb)
Supplementary Table 2
Sequence and position of the STAT92E consensus binding sites in the promoters of the virus-regulated genes vir-1, CG12780, and CG9080. (PDF 76 kb)
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Dostert, C., Jouanguy, E., Irving, P. et al. The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila. Nat Immunol 6, 946–953 (2005). https://doi.org/10.1038/ni1237
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DOI: https://doi.org/10.1038/ni1237
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