Comprehensive Transcriptomic Analysis Identifies Novel Antiviral Factors Against Influenza A Virus Infection.
Comprehensive Transcriptomic Analysis Identifies Novel Antiviral Factors Against Influenza A Virus Infection.
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综合转录组分析鉴定出针对甲型流感病毒感染的新型抗病毒因子
DOI：
10.3389/fimmu.2021.632798
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发表时间：
2021
影响因子：
7.3
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Zhou A;Dong X;Liu M;Tang B
甲型流感病毒（IAV）具有较高的遗传变异，导致传统疫苗和针对病毒蛋白的抗病毒策略效率较低。因此，开发广谱抗病毒治疗药物尤为重要。宿主对 IAV 感染的反应提供了一种有前途的方法，可以将病毒感染中涉及的抗病毒因子识别为潜在的分子药物靶点。在本研究中，为了更好地阐明宿主对IAV反应的分子机制并开发广谱抗病毒药物，我们通过挖掘GEO数据库中的35个微阵列数据集，系统分析了多种人类细胞（包括感染不同亚型IAV的转化上皮细胞和原代上皮细胞）中宿主基因的mRNA表达谱。转录组结果表明，IAV感染导致所有细胞类型中宿主基因表达量的差异，特别是那些参与免疫防御和抗病毒反应的基因。此外，按照P<0.05和|logFC|≥1.5的标准，通过整合基因网络分析，我们发现IAV感染下不同细胞类型中存在一些差异表达基因的重叠。 IFI6、IFIT2、ISG15、HERC5、RSAD2、GBP1、IFIT3、IFITM1、LAMP3、USP18 和 CXCL10 可能是肺泡基底上皮细胞对抗 IAV 感染的关键抗病毒因子，而 BATF2、CXCL10、IFI44L、IL6 和 OAS2 在气道上皮细胞响应不同亚型病毒感染中发挥重要作用。甲型肝炎病毒感染。此外，我们还发现，在感染高或低致病性IAV的人原代上皮细胞中，一些重叠（BATF2、IFI44L、IFI44、HERC5、CXCL10、OAS2、IFIT3、USP18、OAS1、IFIT2）通常上调。此外，不同吞噬细胞类型中IAV感染激活的防御反应相似，包括干扰素调节的信号通路，尽管不同吞噬细胞类型中差异表达的基因表现出很大差异。总而言之，我们的研究结果将有助于更好地理解高致病性或低致病性 IAV 诱导的分子反应的基本模式，并且不同细胞类型中 IAV 上调的重叠基因可能作为早期检测标记或广谱抗病毒靶点。
Influenza A virus (IAV) has a higher genetic variation, leading to the poor efficiency of traditional vaccine and antiviral strategies targeting viral proteins. Therefore, developing broad-spectrum antiviral treatments is particularly important. Host responses to IAV infection provide a promising approach to identify antiviral factors involved in virus infection as potential molecular drug targets. In this study, in order to better illustrate the molecular mechanism of host responses to IAV and develop broad-spectrum antiviral drugs, we systematically analyzed mRNA expression profiles of host genes in a variety of human cells, including transformed and primary epithelial cells infected with different subtypes of IAV by mining 35 microarray datasets from the GEO database. The transcriptomic results showed that IAV infection resulted in the difference in expression of amounts of host genes in all cell types, especially those genes participating in immune defense and antiviral response. In addition, following the criteria of P<0.05 and |logFC|≥1.5, we found that some difference expression genes were overlapped in different cell types under IAV infection via integrative gene network analysis. IFI6, IFIT2, ISG15, HERC5, RSAD2, GBP1, IFIT3, IFITM1, LAMP3, USP18, and CXCL10 might act as key antiviral factors in alveolar basal epithelial cells against IAV infection, while BATF2, CXCL10, IFI44L, IL6, and OAS2 played important roles in airway epithelial cells in response to different subtypes of IAV infection. Additionally, we also revealed that some overlaps (BATF2, IFI44L, IFI44, HERC5, CXCL10, OAS2, IFIT3, USP18, OAS1, IFIT2) were commonly upregulated in human primary epithelial cells infected with high or low pathogenicity IAV. Moreover, there were similar defense responses activated by IAV infection, including the interferon-regulated signaling pathway in different phagocyte types, although the differentially expressed genes in different phagocyte types showed a great difference. Taken together, our findings will help better understand the fundamental patterns of molecular responses induced by highly or lowly pathogenic IAV, and the overlapped genes upregulated by IAV in different cell types may act as early detection markers or broad-spectrum antiviral targets.
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DOI：
10.1084/jem.20161076
发表时间：
2017-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
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DOI：
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发表时间：
2014-07-22
影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1165/rcmb.2010-0157oc
发表时间：
2011-06-01
影响因子：
6.4
作者：
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通讯作者：
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DOI：
10.1126/science.aaa1578
发表时间：
2015-04-24
期刊：
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影响因子：
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通讯作者：
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DOI：
10.1038/s41572-018-0002-y
发表时间：
2018-06-28
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
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通讯作者：
García-Sastre A