Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response.
Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response.
复制标题
DOI：
10.1038/msb.2012.17
复制
发表时间：
2012-05-22
影响因子：
9.9
通讯作者：
Koester, Mario
中科院分区：
文献类型：
--
作者：
Rand, Ulfert;Rinas, Melanie;Schwerk, Johannes;Noehren, Gesa;Linnes, Melanie;Kroeger, Andrea;Flossdorf, Michael;Kaly-Kullai, Kristof;Hauser, Hansjoerg;Hoefer, Thomas;Koester, Mario
关键词：
病毒的细胞识别唤起了I型干扰素（IFN）的分泌（IFNS），这些干扰素通过活细胞成像影响了抗病毒保护状态。刺激的基因（ISG）是单个细胞中的随机事件。细胞中的噪声在核因子-κB的激活和IFN调节因子转录因子的上游产生实验验证表明，面对多层细胞随机性，可靠的抗病毒保护是通过旁分泌反应扩增实现的通过细胞间通信的反应可能是哺乳动物细胞应对信号传导和基因表达中普遍存在的策略。
The cellular recognition of viruses evokes the secretion of type-I interferons (IFNs) that induce an antiviral protective state. By live-cell imaging, we show that key steps of virus-induced signal transduction, IFN-β expression, and induction of IFN-stimulated genes (ISGs) are stochastic events in individual cells. The heterogeneity in IFN production is of cellular—and not viral—origin, and temporal unpredictability of IFN-β expression is largely due to cell-intrinsic noise generated both upstream and downstream of the activation of nuclear factor-κB and IFN regulatory factor transcription factors. Subsequent ISG induction occurs as a stochastic all-or-nothing switch, where the responding cells are protected against virus replication. Mathematical modelling and experimental validation show that reliable antiviral protection in the face of multi-layered cellular stochasticity is achieved by paracrine response amplification. Achieving coherent responses through intercellular communication is likely to be a more widely used strategy by mammalian cells to cope with pervasive stochasticity in signalling and gene expression.
登录
查看更多内容
影响因子：
6.7
作者：
Onoguchi K;Onomoto K;Takamatsu S;Jogi M;Takemura A;Morimoto S;Julkunen I;Namiki H;Yoneyama M;Fujita T
通讯作者：
Fujita T
影响因子：
3.7
作者：
Hu J;Nudelman G;Shimoni Y;Kumar M;Ding Y;López C;Hayot F;Wetmur JG;Sealfon SC
通讯作者：
Sealfon SC
影响因子：
3.7
作者：
Chen S;Short JA;Young DF;Killip MJ;Schneider M;Goodbourn S;Randall RE
通讯作者：
Randall RE
影响因子：
4
作者：
Paixao, Tiago;Carvalho, Tiago P.;Carneiro, Jorge
通讯作者：
Carneiro, Jorge
影响因子：
3.2
作者：
KREUZ, LE;LEVY, AH
通讯作者：
LEVY, AH