Virus-infection or 5'ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1.
Virus-infection or 5'ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1.
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DOI：
10.1371/journal.ppat.1001012
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发表时间：
2010-07-22
期刊：
影响因子：
6.7
通讯作者：
Fujita T
中科院分区：
文献类型：
--
作者：
Onoguchi K;Onomoto K;Takamatsu S;Jogi M;Takemura A;Morimoto S;Julkunen I;Namiki H;Yoneyama M;Fujita T
在感染病毒的细胞中，RIG-I样受体（RLR）识别细胞质病毒RNA，并触发先天的免疫调查，包括产生I型和III型干扰素（IFN）和随后的IFN诱导基因。 （IPS-1，也称为MAV，Visa和Cardif）是RLR的下游分子，在线粒体的外膜上表达。 IPS-1的位置对于其功能至关重要，我们的基本机制是我们在这项研究中的目标。感染和5'PPP-RNA的翻译导致IPS-1的重新分布形成细胞中的斑点骨料。线粒体融合和与IPS-1相关的蛋白质在线粒体的外膜上积极调节RLR介导的先天抗病毒反应，MFN1的特定敲低消除了病毒诱导的IPS-1和IFN生产线粒体通过其融合过程参与IPS-1的分离。
病毒感染，例如影响力和慢性肝炎，是突出的疾病，新兴病毒的爆发对包括人类在内的上等社会而言是严重的问题。 。导致先天抗病毒基因激活的反应。与细胞生长和细胞死亡有关。在本报告中清楚地解释了线粒体融合蛋白MFN1在介导IPS-1重新分布的功能中起着新的作用，这似乎是RLR信号传导的关键步骤。
In virus-infected cells, RIG-I-like receptor (RLR) recognizes cytoplasmic viral RNA and triggers innate immune responses including production of type I and III interferon (IFN) and the subsequent expression of IFN-inducible genes. Interferon-β promoter stimulator 1 (IPS-1, also known as MAVS, VISA and Cardif) is a downstream molecule of RLR and is expressed on the outer membrane of mitochondria. While it is known that the location of IPS-1 is essential to its function, its underlying mechanism is unknown. Our aim in this study was to delineate the function of mitochondria so as to identify more precisely its role in innate immunity. In doing so we discovered that viral infection as well as transfection with 5′ppp-RNA resulted in the redistribution of IPS-1 to form speckle-like aggregates in cells. We further found that Mitofusin 1 (MFN1), a key regulator of mitochondrial fusion and a protein associated with IPS-1 on the outer membrane of mitochondria, positively regulates RLR-mediated innate antiviral responses. Conversely, specific knockdown of MFN1 abrogates both the virus-induced redistribution of IPS-1 and IFN production. Our study suggests that mitochondria participate in the segregation of IPS-1 through their fusion processes. Virus-infections, such as influenza and chronic hepatitis C, are prominent diseases and outbreaks of newly emerging viruses are serious problems for modern society. Higher animals, including humans, are genetically equipped with mechanisms, collectively known as innate immunity, to counteract viral infections. RIG-I-like receptor (RLR), a cytoplasmic sensor, contributes to immune regulation by detecting infections by RNA viruses and triggering a series of responses which results in the activation of innate antiviral genes. Furthermore, it has been demonstrated that IPS-1, the adaptor protein of RLR, is expressed on mitochondrial outer membrane. Mitochondrion is an organelle of prokaryotic cell origin; it regulates energy production, and is involved in cell growth and cell death. Why IPS-1 is located on the mitochondrial outer membrane and how mitochondria are involved in antiviral signaling are yet to be explained clearly. In this report, we discovered that mitochondrial fusion protein MFN1 plays a novel function to mediate IPS-1 redistribution, which appears to be a critical step in RLR signaling.
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DOI：
10.1006/bbrc.2001.4606
发表时间：
2001-03-30
影响因子：
3.1
作者：
Iwamura, T;Yoneyama, M;Fujita, T
通讯作者：
Fujita, T
影响因子：
56.9
作者：
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.
通讯作者：
Sousa, Caetano Reis E.
影响因子：
64.8
作者：
Meylan, E;Curran, J;Tschopp, R
通讯作者：
Tschopp, R
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC