The heat shock response restricts virus infection in Drosophila.
The heat shock response restricts virus infection in Drosophila.
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DOI：
10.1038/srep12758
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发表时间：
2015-08-03
影响因子：
4.6
通讯作者：
van Rij RP
中科院分区：
文献类型：
--
作者：
Merkling SH;Overheul GJ;van Mierlo JT;Arends D;Gilissen C;van Rij RP
先天免疫是抵抗病原体的第一道防线，对受感染宿主的生存至关重要。果蝇是研究病毒致病机制的新兴模型，但抗病毒防御反应仍知之甚少。在这里，我们描述了热休克反应，防止蛋白毒性的细胞机制，作为果蝇抗病毒免疫反应的一个组成部分。果蝇S2细胞和成年果蝇的转录组分析显示，RNA病毒感染后强烈诱导热休克反应。在体外和体内感染不同类型的病毒后，热休克途径成分的动态诱导模式进行了表征。热休克转录因子（Hsf），以及活跃的病毒复制，是必要的诱导的反应。缺乏热休克因子的成年果蝇对病毒感染高度敏感，表明热休克反应在抗病毒防御中的作用。因此，热休克反应的转基因激活延长了感染后的存活时间，并使病毒复制长期控制在不可检测的水平。总之，我们的研究结果建立了热休克反应作为一个重要组成部分的先天抗病毒免疫果蝇。
Innate immunity is the first line of defence against pathogens and is essential for survival of the infected host. The fruit fly Drosophila melanogaster is an emerging model to study viral pathogenesis, yet antiviral defence responses remain poorly understood. Here, we describe the heat shock response, a cellular mechanism that prevents proteotoxicity, as a component of the antiviral immune response in Drosophila. Transcriptome analyses of Drosophila S2 cells and adult flies revealed strong induction of the heat shock response upon RNA virus infection. Dynamic induction patterns of heat shock pathway components were characterized in vitro and in vivo following infection with different classes of viruses. The heat shock transcription factor (Hsf), as well as active viral replication, were necessary for the induction of the response. Hsf-deficient adult flies were hypersensitive to virus infection, indicating a role of the heat shock response in antiviral defence. In accordance, transgenic activation of the heat shock response prolonged survival time after infection and enabled long-term control of virus replication to undetectable levels. Together, our results establish the heat shock response as an important constituent of innate antiviral immunity in Drosophila.