Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity.
Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity.
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DOI：
10.1371/journal.pone.0043031
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fujita T
中科院分区：
文献类型：
--
作者：
Onomoto K;Jogi M;Yoo JS;Narita R;Morimoto S;Takemura A;Sambhara S;Kawaguchi A;Osari S;Nagata K;Matsumiya T;Namiki H;Yoneyama M;Fujita T
视黄酸诱导基因I （RIG-I）样受体（RLRs）作为病毒RNA的细胞质传感器，启动包括I型干扰素（IFN）产生在内的抗病毒反应。rig - 1是如何与病毒RNA相遇和感知的还不清楚。为了解决这个问题，我们使用新产生的抗rig - 1抗体检测了rig - 1在病毒感染反应中的细胞内定位。免疫组织化学分析显示，rlr定位于含有应激颗粒（SG）标记的病毒诱导颗粒中，同时含有病毒RNA和抗病毒蛋白。由于形态和成分的相似性，我们将这些聚集体称为抗病毒应激颗粒（avSGs）。缺乏非结构蛋白1 （NS1）的甲型流感病毒（IAV）可以有效地产生avSGs和IFN，而编码NS1的IAV则很少产生IFN。通过去除SG成分或双链RNA （dsRNA）依赖的蛋白激酶（PKR）来抑制avSGs的形成，导致IFN的产生减少和伴随的病毒复制增强。此外，我们观察到转染dsRNA导致IFN以avsgs依赖的方式产生。这些结果强烈表明，avSG是非自身RNA感知的位点，多种蛋白质的协调在触发抗病毒反应中至关重要。
Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) function as cytoplasmic sensors for viral RNA to initiate antiviral responses including type I interferon (IFN) production. It has been unclear how RIG-I encounters and senses viral RNA. To address this issue, we examined intracellular localization of RIG-I in response to viral infection using newly generated anti-RIG-I antibody. Immunohistochemical analysis revealed that RLRs localized in virus-induced granules containing stress granule (SG) markers together with viral RNA and antiviral proteins. Because of similarity in morphology and components, we termed these aggregates antiviral stress granules (avSGs). Influenza A virus (IAV) deficient in non-structural protein 1 (NS1) efficiently generated avSGs as well as IFN, however IAV encoding NS1 produced little. Inhibition of avSGs formation by removal of either the SG component or double-stranded RNA (dsRNA)-dependent protein kinase (PKR) resulted in diminished IFN production and concomitant enhancement of viral replication. Furthermore, we observed that transfection of dsRNA resulted in IFN production in an avSGs-dependent manner. These results strongly suggest that the avSG is the locus for non-self RNA sensing and the orchestration of multiple proteins is critical in the triggering of antiviral responses.
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