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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Inhibitor κB-like proteins from a polydnavirus inhibit NF-κB activation and suppress the insect immune response
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Inhibitor κB-like proteins from a polydnavirus inhibit NF-κB activation and suppress the insect immune response

机译:来自多核病毒的抑制剂κB样蛋白抑制NF-κB活化并抑制昆虫的免疫反应

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摘要

Complex signaling pathways regulate the innate immune system of insects, with NF-κB transcription factors playing a central role in the activation of antimicrobial peptides and other immune genes. Although numerous studies have characterized the immune responses of insects to pathogens, comparatively little is known about the counterstrategies pathogens have evolved to circumvent host defenses. Among the most potent immunosuppressive pathogens of insects are polydnaviruses that are symbiotically associated with parasitoid wasps. Here, we report that the Microplitis demolitor bracovirus encodes a family of genes with homology to inhibitor κB (IκB) proteins from insects and mammals. Functional analysis of two of these genes, H4 and N5, were conducted in Drosophila S2 cells. Recombinant H4 and N5 greatly reduced the expression of drosomycin and attacin reporter constructs, which are under NF-κB regulation through the Toll and Imd pathways. Coimmunoprecipitation experiments indicated that H4 and N5 bound to the Rel proteins Dif and Relish, and N5 also weakly bound to Dorsal. H4 and N5 also inhibited binding of Dif and Relish to κB sites in the promoters of the drosomycin and cecropin A1 genes. Collectively, these results indicate that H4 and N5 function as IκBs and, circumstantially, suggest that other IκB-like gene family members are involved in the suppression of the insect immune system.
机译:复杂的信号通路调节昆虫的先天免疫系统,其中NF-κB转录因子在抗菌肽和其他免疫基因的激活中起着核心作用。尽管许多研究已经对昆虫对病原体的免疫反应进行了表征,但对病原体已经进化出规避宿主防御的对策知之甚少。在昆虫中最有效的免疫抑制病原体是与寄生性黄蜂共生相关的多脱氧核糖核酸病毒。在这里,我们报道小微支原体Bracovirus编码一个与昆虫和哺乳动物的κB(IκB)蛋白质同源的基因家族。在果蝇S2细胞中对其中两个基因H4和N5进行了功能分析。重组H4和N5大大降低了通过Toll和Imd途径受NF-κB调节的drosomycin和attacin报告基因构建体的表达。免疫共沉淀实验表明,H4和N5与Rel蛋白Dif和Relish结合,而N5也与背面蛋白弱结合。 H4和N5还抑制了Dif和Relish与drosomycin和cecropin A1基因启动子中的κB位点结合。总的来说,这些结果表明H4和N5起着IκB的作用,并且从生物学角度暗示了其他IκB样基因家族成员也参与了昆虫免疫系统的抑制。

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