Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito.
Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito.
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DOI：
10.1371/journal.pone.0053535
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Finley RL Jr
中科院分区：
文献类型：
--
作者：
Mairiang D;Zhang H;Sodja A;Murali T;Suriyaphol P;Malasit P;Limjindaporn T;Finley RL Jr
登革病毒的四种不同血清型是登革热、登革出血热和登革休克综合征的病原体。世界上大约五分之二的人口生活在登革热流行的地区，每年有数千人死于这种病毒。登革热病毒主要通过埃及伊蚊从一个人传播到另一个人。最近的研究已经开始确定登革病毒蛋白如何与宿主蛋白相互作用以介导病毒复制和致病。然而，对这些研究的综合分析表明，许多病毒-宿主蛋白质相互作用仍有待确定，特别是对于蚊子宿主。在这项研究中，我们使用高通量酵母双杂交筛选，以确定蚊子和人类的蛋白质与登革热蛋白质的物理相互作用。我们针对来自登革热的所有四种血清型的蛋白质测试了每种鉴定的宿主蛋白质，以鉴定在血清型之间保守的相互作用。我们使用共亲和纯化测定进一步证实了许多相互作用。与其他大规模筛选一样，我们确定了一些以前检测到的相互作用和许多新的相互作用，使我们更接近完整的宿主-登革热蛋白相互作用组。为了帮助总结和优先考虑进一步研究的数据，我们将我们的相互作用与其他已发表的数据相结合，并确定了宿主-登革热相互作用的一个子集，这些相互作用现在得到了多种形式证据的支持。这些数据对于了解登革热及其宿主之间的相互作用应该是有用的，并可能为药物靶点和病媒控制策略提供候选人。
The four divergent serotypes of dengue virus are the causative agents of dengue fever, dengue hemorrhagic fever and dengue shock syndrome. About two-fifths of the world's population live in areas where dengue is prevalent, and thousands of deaths are caused by the viruses every year. Dengue virus is transmitted from one person to another primarily by the yellow fever mosquito, Aedes aegypti. Recent studies have begun to define how the dengue viral proteins interact with host proteins to mediate viral replication and pathogenesis. A combined analysis of these studies, however, suggests that many virus-host protein interactions remain to be identified, especially for the mosquito host. In this study, we used high-throughput yeast two-hybrid screening to identify mosquito and human proteins that physically interact with dengue proteins. We tested each identified host protein against the proteins from all four serotypes of dengue to identify interactions that are conserved across serotypes. We further confirmed many of the interactions using co-affinity purification assays. As in other large-scale screens, we identified some previously detected interactions and many new ones, moving us closer to a complete host – dengue protein interactome. To help summarize and prioritize the data for further study, we combined our interactions with other published data and identified a subset of the host-dengue interactions that are now supported by multiple forms of evidence. These data should be useful for understanding the interplay between dengue and its hosts and may provide candidates for drug targets and vector control strategies.
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