Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.
Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.
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DOI：
10.1371/journal.pone.0161793
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yokota S
中科院分区：
文献类型：
--
作者：
Hashimoto S;Yamamoto S;Ogasawara N;Sato T;Yamamoto K;Katoh H;Kubota T;Shiraishi T;Kojima T;Himi T;Tsutsumi H;Yokota S
应激颗粒（Stress granules，SG）是由细胞应激（包括病毒感染）诱导的细胞质颗粒聚集体。SG具有相反的抗病毒和前病毒作用，这取决于病毒种类。在病毒感染期间，SG的确切功能尚未完全了解。在这里，我们表明，腮腺炎病毒（MuV）诱导的SGs依赖于蛋白激酶R（PKR）的激活。MuV感染通过激活IFN调节因子3（IRF 3）、视黄酸诱导基因I（RIG-I）和线粒体抗病毒信号传导（MAVS）途径强烈诱导干扰素（IFN）-λ1、2和3以及IFN-β。MuV诱导的IFN在PKR敲低细胞中强烈上调。MuV诱导的SG形成被PKR和SG标记蛋白、Ras-GT3激活蛋白SH 3-domain-binding protein 1和T细胞限制性细胞内抗原-1的敲低所抑制，并且显著增加MuV诱导的IFN-λ1的水平。然而，病毒滴度没有改变抑制SG形成。PKR是MuV感染诱导SGs和调节III型IFN（IFN-λ1）mRNA稳定性所必需的。MuV诱导的SGs部分抑制了MuV产生的III型IFN;然而，有限的抑制不足以抑制细胞培养中MuV的复制。我们的研究结果提供了洞察之间的关系SGs和干扰素生产诱导的MuV感染。
Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.