Global impact of influenza virus on cellular pathways is mediated by both replication-dependent and -independent events
Global impact of influenza virus on cellular pathways is mediated by both replication-dependent and -independent events
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DOI：
10.1128/jvi.75.9.4321-4331.2001
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Katze, MG
中科院分区：
文献类型：
--
作者：
Geiss, GK;An, MC;Katze, MG
流感病毒是普通流感的病原体，是一个世界性的健康问题，具有重大的经济后果。对流感病毒生物学的研究揭示了病毒与其宿主细胞相互作用的复杂机制，因为它抑制细胞蛋白质的合成，逃避先天性抗病毒反应，并促进病毒RNA和蛋白质的产生。随着DNA阵列技术的出现，现在有可能获得病毒如何改变宿主细胞内环境的大规模视图。在这项研究中，通过监测超过4，600个细胞基因的稳态mRNA水平来检查细胞对流感病毒感染的反应。感染活性和灭活流感病毒的细胞基因表达的变化，分别依赖于或独立于病毒复制。病毒复制导致许多细胞mRNA的下调，并且这种作用随着感染后时间的推移而增强。有趣的是，参与蛋白质合成、转录调节和细胞因子信号传导的几个基因被流感病毒复制诱导，这表明一些基因可能在病毒生命周期或宿主细胞的应激反应中发挥重要或辅助作用。灭活病毒诱导的基因表达模式揭示了细胞金属硫蛋白基因的诱导，这可能代表了对病毒诱导的氧化应激的保护性反应。对病毒感染的基因组规模分析将有助于我们了解病毒与宿主相互作用的复杂性，并可能导致发现新的药物靶点或抗病毒疗法。
Influenza virus, the causative agent of the common flu, is a worldwide health problem with significant economic consequences. Studies of influenza virus biology have revealed elaborate mechanisms by which the virus interacts with its host cell as it inhibits the synthesis of cellular proteins, evades the innate antiviral response, and facilitates production of viral RNAs and proteins. With the advent of DNA array technology it is now possible to obtain a large-scale view of how viruses alter the environment within the host cell. In this study, the cellular response to influenza virus infection was examined by monitoring the steady-state mRNA levels for over 4,600 cellular genes. Infections with active and inactivated influenza viruses identified changes in cellular gene expression that were dependent on or independent of viral replication, respectively. Viral replication resulted in the downregulation of many cellular mRNAs, and the effect was enhanced with time postinfection, Interestingly, several genes involved in protein synthesis, transcriptional regulation, and cytokine signaling were induced by influenza virus replication, suggesting that some may play essential or accessory roles in the viral life cycle or the host cell's stress response. The gene expression pattern induced by inactivated viruses revealed induction of the cellular metallothionein genes that may represent a protective response to virus-induced oxidative stress. Genome-scale analyses of virus infections will help us to understand the complexities of virus-host interactions and may lead to the discovery of novel drug targets or antiviral therapies.