早期抗病毒基因表达的单细胞分析揭示了IFNB1随机表达的一个决定因素。
Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression.
作者信息
Doğanay Sultan, Lee Maurice Youzong, Baum Alina, Peh Jessie, Hwang Sun-Young, Yoo Joo-Yeon, Hergenrother Paul J, García-Sastre Adolfo, Myong Sua, Ha Taekjip
机构信息
Center for Computational Biology and Biophysics, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
出版信息
Integr Biol (Camb). 2017 Nov 13;9(11):857-867. doi: 10.1039/c7ib00146k.
Abstract
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.
摘要
视黄酸诱导基因I样受体（RLRs）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对RLRs的转录诱导被认为起到正反馈作用，以进一步放大病毒传感。我们发现，RLRs和其他几种IFN刺激基因（ISGs）在病毒感染早期被诱导，且不依赖于IFN。这些早期ISGs的表达需要IRF3/IRF7，并且它们之间高度相关。同时检测IFNB1、病毒复制酶和ISGs的mRNA，发现表达IFNB1和不表达IFNB1的细胞群体不同，这与早期ISGs的水平高度相关，但与IFN依赖性ISGs和病毒基因表达无关。RLRs的单独表达使IFNB1的表达更加强劲和提前，表明RLRs水平与IFN诱导之间存在因果关系。
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