Functional Analysis of Chicken IRF7 in Response to dsRNA Analog Poly(I:C) by Integrating Overexpression and Knockdown.
Functional Analysis of Chicken IRF7 in Response to dsRNA Analog Poly(I:C) by Integrating Overexpression and Knockdown.
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DOI：
10.1371/journal.pone.0133450
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Kim TH;Zhou H
为了开发新的策略来预防日益剧毒的禽类相关病原体，更好地了解禽类抗病毒反应机制是至关重要的。I型干扰素(IFN)被认为是宿主抗病毒反应的第一道防线；IRF7是干扰素调节因子(IRF)家族的成员，在调节鸡对禽流感病毒感染的免疫反应中发挥重要作用。本研究的目的是在转录组水平上寻找与IRF7调控相关的候选基因和途径，作为阐明IRF7在鸡抗病毒反应中潜在的细胞机制的第一步。建立了IRF7过表达和基因敲除的DF-1细胞系，并用不同的病原体相关分子模式进行刺激。经双链RNA(DsRNA)类似物Poly(I：C)处理后，IRF7过表达细胞株和IRF7基因敲除细胞株的IRF7和I型干扰素表达均发生显著变化。利用基于RNA-seq的转录组分析，我们确定了潜在的新基因，IRF7可能有助于调节宿主对dsRNA的免疫反应；本研究揭示的潜在生物标志物和治疗靶点值得进一步研究。根据我们的结果，我们认为IRF7在禽类的抗病毒反应中可能具有保守的功能活性，并在I型干扰素的调节中发挥关键作用。
In order to develop novel strategies to protect against increasingly virulent bird-linked pathogens, a better understanding of the avian antiviral response mechanism is essential. Type I interferons (IFNs) are recognized as the first line of defense in a host’s antiviral response; and it has been suggested that IRF7, a member of the IFN regulatory factor (IRF) family, plays an important role in modulating the immune response to avian influenza virus infection in chickens. The objective of this study was to identify candidate genes and pathways associated with IRF7 regulation at the transcriptome level as a first step towards elucidating the underlying cellular mechanisms of IRF7 modulation in the chicken antiviral response. IRF7 overexpression and knockdown DF-1 cell lines were established and stimulated by various pathogen-associated molecular patterns. Significant IRF7 and type I IFN expression changes were observed in both the IRF7 overexpression cell line and the IRF7 knockdown cell line upon exposure to the double stranded RNA (dsRNA) analog poly(I:C). Using RNA-seq based transcriptome analysis, we identified potential novel genes that IRF7 may help regulate as part of the host immune response to dsRNA; potential biomarkers and therapeutic targets revealed as a result of this study warrant further investigation. Based on our results, we suggest that IRF7 may have conserved functional activity in the avian antiviral response, and plays a crucial role in type I IFN regulation.