West, Cara C.Silverman, Neal2022-08-232022-08-235/10/182018-07-06<p>PLoS Pathog. 2018 May 10;14(5):e1007020. doi: 10.1371/journal.ppat.1007020. eCollection 2018 May. <a href="https://doi.org/10.1371/journal.ppat.1007020">Link to article on publisher's site</a></p>1553-7366 (Linking)10.1371/journal.ppat.100702029746571https://hdl.handle.net/20.500.14038/40670The fruit fly Drosophila melanogaster is a powerful model system for the study of innate immunity in vector insects as well as mammals. For vector insects, it is particularly important to understand all aspects of their antiviral immune defenses, which could eventually be harnessed to control the transmission of human pathogenic viruses. The immune responses controlling RNA viruses in insects have been extensively studied, but the response to DNA virus infections is poorly characterized. Here, we report that infection of Drosophila with the DNA virus Invertebrate iridescent Virus 6 (IIV-6) triggers JAK-STAT signaling and the robust expression of the Turandots, a gene family encoding small secreted proteins. To drive JAK-STAT signaling, IIV-6 infection more immediately induced expression of the unpaireds, a family of IL-6-related cytokine genes, via a pathway that required one of the three Drosophila p38 homologs, p38b. In fact, both Stat92E and p38b were required for the survival of IIV-6 infected flies. In addition, in vitro induction of the unpaireds required an NADPH-oxidase, and in vivo studies demonstrated Nox was required for induction of TotA. These results argue that ROS production, triggered by IIV-6 infection, leads to p38b activation and unpaired expression, and subsequent JAK-STAT signaling, which ultimately protects the fly from IIV-6 infection.en-USCopyright: © 2018 West, Silverman. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://creativecommons.org/licenses/by/4.0/JAK-STAT signaling cascadeDrosophila melanogasterRNA interferenceViral replicationInsectsViral transmission and infectionInsect vectorsSalmonellosisImmunityImmunology of Infectious DiseaseVirologyJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4482&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/347112450246oapubs/3471