A genome-wide siRNA screen to identify host factors necessary for growth of the parasite Toxoplasma gondii.
A genome-wide siRNA screen to identify host factors necessary for growth of the parasite Toxoplasma gondii.
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DOI：
10.1371/journal.pone.0068129
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Knoll LJ
中科院分区：
文献类型：
--
作者：
Moser LA;Pollard AM;Knoll LJ
刚地弓形虫是一种专性细胞内寄生虫，能够感染几乎所有温血动物的任何有核细胞。宿主细胞因子对寄生虫附着、入侵和复制的重要性了解甚少。我们筛选了一个针对18200个人类个体基因的siRNA文库，以鉴定在弓形虫生长中起作用的宿主蛋白。我们筛选了19个基因，这些基因被siRNA抑制可以持续且显著地降低寄生虫的复制。这19个基因的基因本体类别代表了各种各样的功能，其中一些基因涉及细胞周期、离子通道和受体、g蛋白偶联受体和细胞骨架结构的调节，以及涉及转录、翻译和蛋白质降解的基因。对19个基因中的5个的进一步研究表明，寄主细胞的死亡是导致寄主细胞生长下降的主要原因。我们的研究结果表明，一旦弓形虫入侵并建立感染，宿主细胞的全局变化可能是减少寄生虫复制所必需的。虽然siRNA筛选在其他寄生虫系统中很少使用，但这是第一个描述影响弓形虫复制的宿主蛋白的高通量siRNA筛选的报告。
Toxoplasma gondii is an obligate intracellular parasite that is able to infect virtually any nucleated cell of all warm-blooded animals. The host cell factors important for parasite attachment, invasion, and replication are poorly understood. We screened a siRNA library targeting 18,200 individual human genes in order to identify host proteins with a role in T. gondii growth. Our screen identified 19 genes whose inhibition by siRNA consistently and significantly lowered parasite replication. The gene ontology categories for those 19 genes represented a wide variety of functions with several genes implicated in regulation of the cell cycle, ion channels and receptors, G-protein coupled receptors, and cytoskeletal structure as well as genes involved in transcription, translation and protein degradation. Further investigation of 5 of the 19 genes demonstrated that the primary reason for the reduction in parasite growth was death of the host cell. Our results suggest that once T. gondii has invaded and established an infection, global changes in the host cell may be necessary to reduce parasite replication. While siRNA screens have been used, albeit rarely, in other parasite systems, this is the first report to describe a high-throughput siRNA screen for host proteins that affect T. gondii replication.
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