Genome-Scale RNAi Screen for Host Factors Required for HIV Replication
Genome-Scale RNAi Screen for Host Factors Required for HIV Replication
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DOI：
10.1016/j.chom.2008.10.004
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发表时间：
2008-11-13
影响因子：
30.3
通讯作者：
Espeseth, Amy S.
中科院分区：
文献类型：
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作者：
Zhou, Honglin;Xu, Min;Espeseth, Amy S.
人类免疫缺陷病毒（HIV）-1依赖于宿主细胞机制来支持其复制。为了发现与HIV-1复制相关的细胞因子，我们进行了基因组规模的siRNA筛选，揭示了超过311个宿主因子，其中包括267个以前与HIV无关的因子。令人惊讶的是，这些基因和最近描述的HIV依赖性因素之间几乎没有重叠。然而，对两种筛选中鉴定的基因的分析揭示了几种相关途径或蛋白复合物的重叠，包括SP1/介体复合物和NF-κ B信号通路。在敲低细胞mRNA后，使用鉴定基因的一个子集的cDNA来拯救HIV复制，提供了以下六个基因是先前未表征的HIV宿主因子的强有力证据：AKT 1、PRKAA 1、CD 97、NEIL 3、BMP 2K和SERPINB 6。这项研究强调了大规模功能丧失筛选在发现宿主-病原体相互作用方面的能力和缺点。
Human immunodeficiency virus (HIV)-1 depends on the host cell machinery to support its replication. To discover cellular factors associated with HIV-1 replication, we conducted a genome-scale siRNA screen, revealing more than 311 host factors, including 267 that were not previously linked to HIV. Surprisingly, there was little overlap between these genes and the HIV dependency factors described recently. However, an analysis of the genes identified in both screens revealed overlaps in several of the associated pathways or protein complexes, including the SP1/mediator complex and the NF-kappa B signaling pathway. cDNAs for a subset of the identified genes were used to rescue HIV replication following knockdown of the cellular mRNA providing strong evidence that the following six genes are previously uncharacterized host factors for HIV: AKT1, PRKAA1, CD97, NEIL3, BMP2K, and SERPINB6. This study highlights both the power and shortcomings of large scale loss-of-function screens in discovering host-pathogen interactions.