Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3.
Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3.
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发表时间：
2005
期刊：
影响因子：
64.5
通讯作者：
Rashu B. Seth;Lijun Sun;Chee-Kwee Ea;Zhijian J. Chen
中科院分区：
文献类型：
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作者：
Rashu B. Seth;Lijun Sun;Chee-Kwee Ea;Zhijian J. Chen
病毒感染通过激活转录因子NF-kappaB和IRF3来触发宿主的先天免疫反应，这些转录因子协调调节I型干扰素的表达，如干扰素-β。在此，我们报道了一种名为MAVS(线粒体抗病毒信号)的新蛋白的鉴定，它介导了病毒感染时NF-kappaB和IRF3的激活。通过RNA干扰沉默MAVS的表达可以消除病毒对NF-kappaB和IRF3的激活，从而允许病毒复制。反之，MAVS的过表达通过激活核因子-kappaB和IRF3来诱导干扰素-β的表达，从而增强抗病毒免疫。上位性实验表明，MAV是IRF 3和IkappaB磷酸化所必需的，并在RIG-I下游发挥作用，RIG-I是病毒RNA的细胞内受体。MAVS含有一个N端卡片样结构域和一个C端跨膜结构域，这两个结构域对MAVS信号转导都是必不可少的。跨膜结构域针对线粒体，暗示了线粒体在先天免疫中的新作用。
Viral infection triggers host innate immune responses through activation of the transcription factors NF-kappaB and IRF 3, which coordinately regulate the expression of type-I interferons such as interferon-beta (IFN-beta). Herein, we report the identification of a novel protein termed MAVS (mitochondrial antiviral signaling), which mediates the activation of NF-kappaB and IRF 3 in response to viral infection. Silencing of MAVS expression through RNA interference abolishes the activation of NF-kappaB and IRF 3 by viruses, thereby permitting viral replication. Conversely, overexpression of MAVS induces the expression of IFN-beta through activation of NF-kappaB and IRF 3, thus boosting antiviral immunity. Epistasis experiments show that MAVS is required for the phosphorylation of IRF 3 and IkappaB and functions downstream of RIG-I, an intracellular receptor for viral RNA. MAVS contains an N-terminal CARD-like domain and a C-terminal transmembrane domain, both of which are essential for MAVS signaling. The transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity.