Mapping protein interactions between Dengue virus and its human and insect hosts.
Mapping protein interactions between Dengue virus and its human and insect hosts.
复制标题
在登革热病毒与其人类和昆虫宿主之间绘制蛋白质相互作用。
DOI：
10.1371/journal.pntd.0000954
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发表时间：
2011-02-15
影响因子：
3.8
通讯作者：
Gomez SM
中科院分区：
文献类型：
--
作者：
Doolittle JM;Gomez SM
登革热是一种日益严重的节肢动物传播的病毒性疾病，全世界每年至少有 5000 万例病例。与其他病毒病原体一样，登革热病毒依赖其宿主来执行病毒生存和复制所需的大部分功能。为了获得成功，登革热必须操纵宿主细胞的生物过程以实现其自身目的，同时避免被免疫系统消除。病毒与其宿主之间的蛋白质-蛋白质相互作用是登革热连接和利用这些宿主细胞途径和过程的途径之一。我们采用了一种计算方法来预测登革热病毒 (DENV) 与其宿主智人和昆虫媒介埃及伊蚊之间的相互作用。我们的方法基于 DENV 和宿主蛋白之间的结构相似性，并结合文献中的知识来进一步支持预测的子集。我们预测 DENV 与人类之间有超过 4,000 次相互作用，以及 DENV 与埃及伊蚊之间有 176 次相互作用。基于共享基因本体细胞成分注释的额外过滤将人类的预测数量减少到大约 2,000 个，埃及伊蚊的预测数量减少到 18 个。从文献中提取的 19 种经过实验验证的 DENV 与人类之间的相互作用中，该方法能够预测近一半 (9)。其他预测表明病毒和宿主蛋白之间存在与干扰素信号传导、转录调节、应激和未折叠蛋白反应相关的特定相互作用。登革热病毒通过与宿主蛋白质相互作用网络的特定相互作用来操纵细胞过程以发挥其优势。这里提出的相互作用网络为进一步实验研究 DENV 生命周期以及潜在的治疗靶点提供了一组假设。登革热病毒（DENV）是世界热带和亚热带地区的主要疾病负担，近年来病例数量有所增加。 DENV 通过受感染的蚊子（通常是埃及伊蚊）的叮咬传播给人类，之后它开始在人类细胞内进行感染和复制生命周期。为了执行病毒入侵、复制和传播所需的分子功能，DENV 编码的蛋白质必须与这两种宿主中的蛋白质网络相互作用并改变其行为。在这项工作中，我们使用基于蛋白质结构的计算方法来预测 DENV 与其人类和昆虫宿主之间的相互作用。我们预测了许多相互作用，其中许多相互作用涉及已知的细胞死亡、压力和免疫系统途径。对这些预测的蛋白质-蛋白质相互作用的进一步研究应该提供对抗人类这种疾病的临床表现的目标以及针对蚊子媒介的干预点。
Dengue fever is an increasingly significant arthropod-borne viral disease, with at least 50 million cases per year worldwide. As with other viral pathogens, dengue virus is dependent on its host to perform the bulk of functions necessary for viral survival and replication. To be successful, dengue must manipulate host cell biological processes towards its own ends, while avoiding elimination by the immune system. Protein-protein interactions between the virus and its host are one avenue through which dengue can connect and exploit these host cellular pathways and processes. We implemented a computational approach to predict interactions between Dengue virus (DENV) and both of its hosts, Homo sapiens and the insect vector Aedes aegypti. Our approach is based on structural similarity between DENV and host proteins and incorporates knowledge from the literature to further support a subset of the predictions. We predict over 4,000 interactions between DENV and humans, as well as 176 interactions between DENV and A. aegypti. Additional filtering based on shared Gene Ontology cellular component annotation reduced the number of predictions to approximately 2,000 for humans and 18 for A. aegypti. Of 19 experimentally validated interactions between DENV and humans extracted from the literature, this method was able to predict nearly half (9). Additional predictions suggest specific interactions between virus and host proteins relevant to interferon signaling, transcriptional regulation, stress, and the unfolded protein response. Dengue virus manipulates cellular processes to its advantage through specific interactions with the host's protein interaction network. The interaction networks presented here provide a set of hypothesis for further experimental investigation into the DENV life cycle as well as potential therapeutic targets. Dengue virus (DENV) represents a major disease burden in tropical and subtropical regions of the world, and has shown an increase in the number of cases in recent years. DENV is transmitted to humans through the bite of an infected mosquito, typically Aedes aegypti, after which it begins the infection and replication lifecycle within human cells. To perform the molecular functions required for invasion, replication, and spread of the virus, proteins encoded by DENV must interact with and alter the behavior of protein networks in both of these hosts. In this work, we used a computational method based on protein structures to predict interactions between DENV and its human and insect hosts. We predict numerous interactions, with many involved in known cell death, stress, and immune system pathways. Further investigation of these predicted protein-protein interactions should provide targets to combat the clinical manifestations of this disease in humans as well as points of intervention focused within the mosquito vector.
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影响因子：
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