Viral degradasome hijacks mitochondria to suppress innate immunity
Viral degradasome hijacks mitochondria to suppress innate immunity
复制标题
DOI：
10.1038/cr.2013.98
复制
发表时间：
2013-08-01
期刊：
影响因子：
44.1
通讯作者：
Barik, Sailen
中科院分区：
文献类型：
--
作者：
Goswami, Ramansu;Majumdar, Tanmay;Barik, Sailen
宿主的先天免疫和病原体逃避它的能力之间的平衡强烈影响致病性和毒力。呼吸道合胞病毒（RSV）的两种非结构（NS）蛋白NS 1和NS 2是RSV毒力所必需的。它们一起通过降解或抑制IFN诱导或应答途径所需的多种细胞因子，包括RIG-I、IRF 3、IRF 7、TBK 1和STAT 2，强烈抑制I型干扰素（IFN）介导的宿主细胞先天免疫。在这里，我们提供的证据表明存在一个大的和异质性的降解复合物组装的NS蛋白，我们命名为“NS-降解体”（NSD）。NSD的大小大致为300-750 kD，其降解活性通过加入纯化的线粒体而增强。在细胞内，大多数NS蛋白和NSD的底物在RSV感染后易位到线粒体。遗传和药理学证据表明，先天免疫的最佳抑制需要线粒体MAVS和线粒体运动。总之，我们提出了一个新的范例，其中线粒体，已知是重要的先天免疫激活的主机，也是重要的先天免疫的病毒抑制。
The balance between the innate immunity of the host and the ability of a pathogen to evade it strongly influences pathogenesis and virulence. The two nonstructural (NS) proteins, NS1 and NS2, of respiratory syncytial virus (RSV) are critically required for RSV virulence. Together, they strongly suppress the type I interferon (IFN)-mediated innate immunity of the host cells by degrading or inhibiting multiple cellular factors required for either IFN induction or response pathways, including RIG-I, IRF3, IRF7, TBK1 and STAT2. Here, we provide evidence for the existence of a large and heterogeneous degradative complex assembled by the NS proteins, which we named "NS-degradasome" (NSD). The NSD is roughly similar to 300-750 kD in size, and its degradative activity was enhanced by the addition of purified mitochondria in vitro. Inside the cell, the majority of the NS proteins and the substrates of the NSD translocated to the mitochondria upon RSV infection. Genetic and pharmacological evidence shows that optimal suppression of innate immunity requires mitochondrial MAVS and mitochondrial motility. Together, we propose a novel paradigm in which the mitochondria, known to be important for the innate immune activation of the host, are also important for viral suppression of the innate immunity.