Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Cell. 2009 Dec 24;139(7):1255-67. doi: 10.1016/j.cell.2009.12.018.
During the course of a viral infection, viral proteins interact with an array of host proteins and pathways. Here, we present a systematic strategy to elucidate the dynamic interactions between H1N1 influenza and its human host. A combination of yeast two-hybrid analysis and genome-wide expression profiling implicated hundreds of human factors in mediating viral-host interactions. These factors were then examined functionally through depletion analyses in primary lung cells. The resulting data point to potential roles for some unanticipated host and viral proteins in viral infection and the host response, including a network of RNA-binding proteins, components of WNT signaling, and viral polymerase subunits. This multilayered approach provides a comprehensive and unbiased physical and regulatory model of influenza-host interactions and demonstrates a general strategy for uncovering complex host-pathogen relationships.
在病毒感染过程中，病毒蛋白与一系列宿主蛋白和途径相互作用。在这里，我们提出了一种系统的策略来阐明 H1N1 流感病毒与其人类宿主之间的动态相互作用。酵母双杂交分析和全基因组表达谱分析相结合，鉴定了数百个人类因子在介导病毒-宿主相互作用中发挥作用。然后通过在原代肺细胞中进行耗竭分析来对这些因子进行功能检查。由此产生的数据表明，一些意想不到的宿主和病毒蛋白在病毒感染和宿主反应中可能发挥作用，包括 RNA 结合蛋白网络、WNT 信号通路的组成部分和病毒聚合酶亚基。这种多层次的方法提供了一个全面和无偏倚的流感病毒-宿主相互作用的物理和调控模型，并展示了揭示复杂宿主-病原体关系的一般策略。
