| 论文题目: | Robust expression of vault RNAs induced by influenza A virus plays a critical role in suppression of PKR-mediated innate immunity |
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| 作者: | Li Fang, Chen Yuhai, Zhang Zhaoyuan, Ouyang Jing, Wang Yi, Yan Ruoxiang, Huang Shile, Gao George Fu, Guo Guijie, and Chen Ji-Long*. |
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| 刊物名称: | Nucleic Acids Res |
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| 年份: | 2015 |
| 影响因子: | 8.867 |
| 论文下载: | 下载地址 |
| 摘要: | Protein kinase R (PKR) is a vital component of host innate immunity against viral infection. However, the mechanism underlying inactivation of PKR by in fl uenza A virus (IAV) remains elusive. Here, we found that vault RNAs (vtRNAs) were greatly induced in A549 cells and mouse lungs after infection with IAV. The viral NS1 protein was shown to be the inducer triggering the upregulation of vtRNAs. Importantly, silencing vtRNA in A549 cells significantly inhibited IAV replication, whereas overexpression of vtRNAs markedly promoted the viral replication. Furthermore, in vivo studies showed that disrupting vtRNA expression in mice significantly decreased IAV replication in infected lungs. The vtRNA knockdown animals exhibited significantly enhanced resistance to IAV infection, as evidenced by attenuated acute lung injury and spleen atrophy and consequently increased survival rates. Interestingly, vtRNAs promoted viral replication through repressing the activation of PKR and the subsequent antiviral interferon response. In addition, increased expression of vtRNAs was required for efficient suppression of PKR by NS1 during IAV infection. Moreover, vtRNAs were also significantly upregulated by infections of several other viruses and involved in the inactivation of PKR signaling by these viruses. These results reveal a novel mechanism by which some viruses circumvent PKR-mediated innate immunity. |
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