A Long Noncoding RNA Regulates Hepatitis C Virus Infection Through Interferon Alpha-Inducible Protein 6.
A Long Noncoding RNA Regulates Hepatitis C Virus Infection Through Interferon Alpha-Inducible Protein 6.
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长非编码RNA通过干扰素α诱导蛋白6调节丙型肝炎病毒感染
DOI：
10.1002/hep.30266
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Chung RT
中科院分区：
文献类型：
--
作者：
Liu X;Duan X;Holmes JA;Li W;Lee SH;Tu Z;Zhu C;Salloum S;Lidofsky A;Schaefer EA;Cai D;Li S;Wang H;Huang Y;Zhao Y;Yu ML;Xu Z;Chen L;Hong J;Lin W;Chung RT
长非编码RNA(LncRNAs)在许多重要的细胞过程中起着重要的调节作用。然而，lncRNAs调节病毒感染和宿主免疫反应的机制尚不清楚。我们试图探索lncRNA对丙型肝炎病毒感染和干扰素应答的调控。我们在有或没有干扰素α处理的Huh7.5.1细胞中进行了RNAseq。用CRISPR/Cas9引导RNA(GRNA)敲除所选基因。构建启动子克隆，用分泌对双发光实验检测相关干扰素刺激基因(ISGs)活性。我们根据预测的二级结构构建了干扰素诱导的lncRNA RP11-288L9.4(lncRNA-IFI6)的全长和4个缺失突变体。用qRT-PCR和Western印迹方法检测Huh7.5.1细胞和原代人肝细胞(PHHs)中选择的基因mRNAs及其蛋白与丙型肝炎病毒感染的关系。我们从RNAseq获得了7901个LncRNA。1062个宿主编码的lncRNA被干扰素α处理后有明显的差异调节。我们发现，与阴性的gRNA对照相比，lncRNA-IFI6gRNA显著抑制了丙型肝炎病毒的感染。在JFH1感染的Huh7.5.1细胞和PHH中，经lncRNA-IFI6 gRNA编辑后的抗病毒ISG IFI6的表达显著高于阴性gRNA对照。我们观察到，lncRNA-IFI6对丙型肝炎病毒的调节不依赖于JAK-STAT信号。LncRNA-IFI6通过组蛋白修饰负性调节IFI6启动子的功能。过表达截断的空间域或全长的lncRNA-IFI6抑制了IFI6的表达并增加了丙型肝炎病毒的复制。一种新的lncRNA，lncRNA-IFI6，在JFH1丙型肝炎病毒感染模型中调节抗病毒先天免疫。LncRNA-IFI6独立于JAK-STAT途径调节丙型肝炎病毒感染。IncRNA-IFI6通过其空间结构域激活启动子和修饰IFI6的组蛋白，发挥其调控功能。
Long non-coding RNAs (lncRNAs) play a critical role in the regulation of many important cellular processes. However, the mechanisms by which lncRNAs regulate viral infection and host immune responses are not well understood. We sought to explore lncRNA regulation of HCV infection and interferon response. We performed RNAseq in Huh7.5.1 cells with or without IFNα treatment. CRISPR/Cas9 guide RNA (gRNA) was used to knock out selected genes. The promoter clones were constructed, and the activity of related interferon-stimulated genes (ISGs) were detected by the secrete-pair dual luminescence assay. We constructed the full-length and four deletion mutants of an interferon-induced lncRNA RP11–288L9.4 (lncRNA-IFI6) based on predicted secondary structure. Selected gene mRNAs and their proteins, together with HCV infection, in Huh7.5.1 cells and Primary Human Hepatocytes (PHHs) were monitored by qRT-PCR and Western blot. We obtained 7901 lncRNAs from RNAseq. 1062 host-encoded lncRNAs were significantly differentially regulated by IFNα treatment. We found that lncRNA-IFI6 gRNA significantly inhibited HCV infection compared to negative gRNA control. The expression of the antiviral ISG IFI6 was significantly increased following lncRNA-IFI6 gRNA editing compared to negative gRNA control in JFH1-infected Huh7.5.1 cells and PHHs. We observed that lncRNA-IFI6 regulation of HCV was independent of JAK-STAT signaling. lncRNA-IFI6 negatively regulated IFI6 promoter function through histone modification. Overexpression of the truncated spatial domain or full-length lncRNA-IFI6 inhibited IFI6 expression and increased HCV replication. A novel lncRNA, lncRNA-IFI6, regulates antiviral innate immunity in the JFH1 HCV infection model. lncRNA-IFI6 regulates HCV infection independently of the JAK-STAT pathway. lncRNA-IFI6 exerts its regulatory function via promoter activation and histone modification of IFI6 through its spatial domain.
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影响因子：
14.9
作者：
Ho TT;Zhou N;Huang J;Koirala P;Xu M;Fung R;Wu F;Mo YY
通讯作者：
Mo YY
丙型肝炎病毒感染中的先天免疫反应。
影响因子：
9
作者：
Li, Kui;Lemon, Stanley M.
通讯作者：
Lemon, Stanley M.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.7
作者：
Arnaud N;Dabo S;Akazawa D;Fukasawa M;Shinkai-Ouchi F;Hugon J;Wakita T;Meurs EF
通讯作者：
Meurs EF
DOI：
10.1126/science.1240925
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carpenter S;Aiello D;Atianand MK;Ricci EP;Gandhi P;Hall LL;Byron M;Monks B;Henry-Bezy M;Lawrence JB;O'Neill LA;Moore MJ;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA