Response of the mosquito protein interaction network to dengue infection
Response of the mosquito protein interaction network to dengue infection
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DOI：
10.1186/1471-2164-11-380
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发表时间：
2010-06-16
期刊：
影响因子：
4.4
通讯作者：
Xi, Zhiyong
中科院分区：
文献类型：
--
作者：
Guo, Xiang;Xu, Yao;Xi, Zhiyong
背景：世界五分之二的人口面临登革热的风险。由于缺乏有效的药物和疫苗，病媒控制成为主要的干预工具。了解登革热病毒 (DENV) 宿主相互作用对于开发新型控制策略至关重要。人类和蚊子宿主基因组序列的可用性极大地促进了 DENV-宿主相互作用的全基因组研究。结果：我们使用计算方法开发了蚊子蛋白相互作用网络的初稿。该加权网络包括 4,214 个埃及伊蚊蛋白，具有 10,209 个相互作用，其中 3,500 个蛋白连接成一个互连的无标度网络。我们展示了该网络在蚊子蛋白的进一步注释和通路串扰剖析中的应用。使用基于物理相互作用测定、全基因组 RNA 干扰 (RNAi) 筛选和微阵列测定的三个数据集，我们鉴定了 714 种假定的 DENV 相关蚊子蛋白。对网络中这些蛋白质的综合分析突出了由高度互连的蛋白质组成的四个区域，这些区域在复制/转录/翻译（RTT）、免疫、运输和代谢中具有密切相关的功能。通过 RNAi 介导的基因沉默进一步选择推定的 DENV 相关蛋白进行验证，并且对于十分之五 (50.0%) 随机选择的基因，蚊子中肠中的登革热病毒滴度显着降低。结论：我们的结果表明蚊子和人类对 DENV 存在共同的宿主需求。我们讨论了我们的发现对于药物干预和蚊子基因改造以阻止登革热传播的重要性。
Background: Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions.Results: We developed the first draft of the mosquito protein interaction network using a computational approach. The weighted network includes 4,214 Aedes aegypti proteins with 10,209 interactions, among which 3,500 proteins are connected into an interconnected scale-free network. We demonstrated the application of this network for the further annotation of mosquito proteins and dissection of pathway crosstalk. Using three datasets based on physical interaction assays, genome-wide RNA interference (RNAi) screens and microarray assays, we identified 714 putative DENV-associated mosquito proteins. An integrated analysis of these proteins in the network highlighted four regions consisting of highly interconnected proteins with closely related functions in each of replication/transcription/ translation (RTT), immunity, transport and metabolism. Putative DENV-associated proteins were further selected for validation by RNAi-mediated gene silencing, and dengue viral titer in mosquito midguts was significantly reduced for five out of ten (50.0%) randomly selected genes.Conclusions: Our results indicate the presence of common host requirements for DENV in mosquitoes and humans. We discuss the significance of our findings for pharmacological intervention and genetic modification of mosquitoes for blocking dengue transmission.