Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
PLoS Pathog. 2018 May 10;14(5):e1007020. doi: 10.1371/journal.ppat.1007020. eCollection 2018 May.
The 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.
果蝇 Drosophila melanogaster 是研究媒介昆虫和哺乳动物固有免疫的强大模式生物。对于媒介昆虫来说，了解其抗病毒免疫防御的各个方面尤为重要，因为这最终可能被用于控制人类致病病毒的传播。昆虫中控制 RNA 病毒的免疫反应已经得到了广泛的研究，但对 DNA 病毒感染的反应却知之甚少。在这里，我们报告说，感染 DNA 病毒虹彩病毒 6（IIV-6）会触发 JAK-STAT 信号通路，并强烈表达 Turandots，这是一个编码小分泌蛋白的基因家族。为了驱动 JAK-STAT 信号通路，IIV-6 感染更直接地诱导了未配对的表达，这是一组与白细胞介素 6 相关的细胞因子基因，通过一条途径需要三种果蝇 p38 同源物之一 p38b。事实上，Stat92E 和 p38b 都需要 IIV-6 感染的果蝇才能存活。此外，未配对的体外诱导需要 NADPH 氧化酶，体内研究表明 Nox 对于 TotA 的诱导是必需的。这些结果表明，IIV-6 感染引发的 ROS 产生导致 p38b 激活和未配对表达，以及随后的 JAK-STAT 信号通路，最终保护果蝇免受 IIV-6 感染。
