Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens.
Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens.
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DOI：
10.1186/1743-422x-7-82
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发表时间：
2010-04-28
期刊：
影响因子：
4.8
通讯作者：
Gomez SM
中科院分区：
文献类型：
--
作者：
Doolittle JM;Gomez SM
在感染过程中，像HIV-1这样的病毒必须进入细胞，到达可以劫持宿主机器转录基因和翻译蛋白质的地方，组装，然后再次离开细胞，同时避开宿主的免疫系统。因此，成功的感染取决于病原体操纵其感染的生物体的生物途径和过程的能力。hiv编码蛋白和人类蛋白之间的相互作用提供了一种途径，通过这种途径，HIV-1可以连接到细胞通路来执行这些生存过程。基于9种HIV-1蛋白与已知相互作用的人类蛋白的结构相似性，我们开发并应用了一种计算方法来预测HIV与人类蛋白之间的相互作用。使用来自RNAi研究的功能数据作为过滤器，我们在HIV蛋白和406种独特的人类蛋白之间产生了2000多种相互作用预测。基于Gene Ontology细胞成分注释的额外过滤将预测数量减少到涉及137个人类蛋白质的502个相互作用。我们发现许多已知的相互作用以及基于支持基因本体和文献证据的新相互作用显示出显著的功能相关性。了解HIV-1与其人类宿主之间的相互作用将有助于了解病毒的生命周期以及这种病毒能够操纵其宿主的方式。这里显示的结果提供了一组潜在的相互作用，可用于进一步的实验操作以及治疗干预的潜在目标。
In the course of infection, viruses such as HIV-1 must enter a cell, travel to sites where they can hijack host machinery to transcribe their genes and translate their proteins, assemble, and then leave the cell again, all while evading the host immune system. Thus, successful infection depends on the pathogen's ability to manipulate the biological pathways and processes of the organism it infects. Interactions between HIV-encoded and human proteins provide one means by which HIV-1 can connect into cellular pathways to carry out these survival processes. We developed and applied a computational approach to predict interactions between HIV and human proteins based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions. Using functional data from RNAi studies as a filter, we generated over 2000 interaction predictions between HIV proteins and 406 unique human proteins. Additional filtering based on Gene Ontology cellular component annotation reduced the number of predictions to 502 interactions involving 137 human proteins. We find numerous known interactions as well as novel interactions showing significant functional relevance based on supporting Gene Ontology and literature evidence. Understanding the interplay between HIV-1 and its human host will help in understanding the viral lifecycle and the ways in which this virus is able to manipulate its host. The results shown here provide a potential set of interactions that are amenable to further experimental manipulation as well as potential targets for therapeutic intervention.