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Influenza Virus Exploits an Interferon-Independent lncRNA to Preserve Viral RNA Synthesis through Stabilizing Viral RNA Polymerase PB1.
Cell Reports ( IF 7.5 ) Pub Date : 2019-06-11 , DOI: 10.1016/j.celrep.2019.05.036 Jing Wang 1 , Yongxin Zhang 1 , Quanjie Li 1 , Jianyuan Zhao 1 , Dongrong Yi 1 , Jiwei Ding 1 , Fei Zhao 2 , Siqi Hu 2 , Jinming Zhou 1 , Tao Deng 2 , Xiaoyu Li 1 , Fei Guo 2 , Chen Liang 3 , Shan Cen 1
Cell Reports ( IF 7.5 ) Pub Date : 2019-06-11 , DOI: 10.1016/j.celrep.2019.05.036 Jing Wang 1 , Yongxin Zhang 1 , Quanjie Li 1 , Jianyuan Zhao 1 , Dongrong Yi 1 , Jiwei Ding 1 , Fei Zhao 2 , Siqi Hu 2 , Jinming Zhou 1 , Tao Deng 2 , Xiaoyu Li 1 , Fei Guo 2 , Chen Liang 3 , Shan Cen 1
Affiliation
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Long noncoding RNAs (lncRNAs) participate in host antiviral defense by modulating immune responses. However, it remains largely unexplored how viruses exploit interferon (IFN)-independent host lncRNAs to facilitate viral replication. Here, we have identified a group of human lncRNAs that modulate influenza A virus (IAV) replication in a loss-of-function screen and found that an IFN-independent lncRNA, called IPAN, is hijacked by IAV to assist IAV replication. IPAN is specifically induced by IAV infection independently of IFN and associates with and stabilizes viral RNA-dependent RNA polymerase PB1, enabling efficient viral RNA synthesis. Silencing IPAN results in PB1 degradation and severely impairs viral infection. Therefore, our data unveil an important role of host lncRNAs in promoting viral replication by modulating viral protein stability. Our findings may open avenues to the development of antiviral therapeutics.
中文翻译：
流感病毒利用稳定病毒RNA聚合酶PB1的干扰素依赖性lncRNA来保留病毒RNA的合成。
长非编码RNA（lncRNA）通过调节免疫应答参与宿主抗病毒防御。但是，在很大程度上，病毒如何利用独立于干扰素（IFN）的宿主lncRNA促进病毒复制尚无定论。在这里，我们确定了一组在功能丧失筛选中调节甲型流感病毒（IAV）复制的人类lncRNA，并发现IAV劫持了独立于IFN的lncRNA，称为IPAN，以协助IAV复制。IPAN由IAV感染独立于IFN特异性诱导，并与病毒RNA依赖性RNA聚合酶PB1缔合并使其稳定，从而实现了有效的病毒RNA合成。使IPAN沉默会导致PB1降解并严重损害病毒感染。因此，我们的数据揭示了宿主lncRNA在通过调节病毒蛋白稳定性来促进病毒复制中的重要作用。
更新日期：2019-06-12
中文翻译：
流感病毒利用稳定病毒RNA聚合酶PB1的干扰素依赖性lncRNA来保留病毒RNA的合成。
长非编码RNA（lncRNA）通过调节免疫应答参与宿主抗病毒防御。但是，在很大程度上，病毒如何利用独立于干扰素（IFN）的宿主lncRNA促进病毒复制尚无定论。在这里，我们确定了一组在功能丧失筛选中调节甲型流感病毒（IAV）复制的人类lncRNA，并发现IAV劫持了独立于IFN的lncRNA，称为IPAN，以协助IAV复制。IPAN由IAV感染独立于IFN特异性诱导，并与病毒RNA依赖性RNA聚合酶PB1缔合并使其稳定，从而实现了有效的病毒RNA合成。使IPAN沉默会导致PB1降解并严重损害病毒感染。因此，我们的数据揭示了宿主lncRNA在通过调节病毒蛋白稳定性来促进病毒复制中的重要作用。
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