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Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression
Integrative Biology ( IF 2.5 ) Pub Date : 2017-10-30 00:00:00 , DOI: 10.1039/c7ib00146k
Sultan Doğanay 1, 2, 3, 4, 5 , Maurice Youzong Lee 2, 3, 4, 5 , Alina Baum 4, 6, 7, 8, 9 , Jessie Peh 2, 3, 4, 10 , Sun-Young Hwang 11, 12, 13, 14 , Joo-Yeon Yoo 11, 12, 13, 14 , Paul J. Hergenrother 2, 3, 4, 10 , Adolfo García-Sastre 4, 6, 7, 8, 15 , Sua Myong 2, 3, 4, 16 , Taekjip Ha 1, 2, 3, 4, 5
Affiliation  

RIG-I-like receptors (RLRs) are cytoplasmic sensors of viral RNA that trigger the signaling cascade that leads to type I interferon (IFN) production. Transcriptional induction of RLRs by IFN is believed to play the role of positive feedback to further amplify viral sensing. We found that RLRs and several other IFN-stimulated genes (ISGs) are induced early in viral infection independent of IFN. Expression of these early ISGs requires IRF3/IRF7 and is highly correlated amongst them. Simultaneous detection of mRNA of IFNB1, viral replicase, and ISGs revealed distinct populations of IFNB1 expressing and non-expressing cells which are highly correlated with the levels of early ISGs but are uncorrelated with IFN-dependent ISGs and viral gene expression. Individual expression of RLRs made IFNB1 expression more robust and earlier, suggesting a causal relation between levels of RLR and induction of IFN.

中文翻译:

早期抗病毒基因表达的单细胞分析揭示了随机IFNB1表达的决定因素

RIG-I样受体(RLR)是病毒RNA的胞质传感器,可触发导致I型干扰素(IFN)产生的信号级联反应。IFN介导的RLR转录诱导被认为起正反馈作用,以进一步扩大病毒感测。我们发现RLR和其他几个IFN刺激的基因(ISGs)是在病毒感染的早期独立于IFN诱导的。这些早期ISG的表达需要IRF3 / IRF7,并且在它们之间高度相关。同时检测IFNB1,mRNA复制酶和ISG的mRNA,发现与早期ISG的水平高度相关但与IFN依赖性ISG和病毒基因表达无关的IFNB1表达和非表达细胞群明显不同。RLR的个别表达IFNB1表达更稳定且更早,表明RLR水平与IFN诱导之间存在因果关系。
更新日期:2017-11-13
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