Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling
Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling
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DOI：
10.1101/819482
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发表时间：
2019-10
期刊：
影响因子：
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通讯作者：
M. Brownsword;Nicole Doyle;Michèle Brocard;Nicolas Locker;Helena J. Maier
中科院分区：
文献类型：
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作者：
M. Brownsword;Nicole Doyle;Michèle Brocard;Nicolas Locker;Helena J. Maier
病毒必须劫持细胞翻译机制以有效表达病毒基因。在许多情况下，这受到细胞应激反应的阻碍。这些应激反应迅速重新定位和重新利用翻译机制，导致翻译的全局抑制和停滞的48S mRNP聚集到称为应激颗粒的细胞质病灶中。这导致所有mRNA的翻译沉默，排除那些有益于细胞解决特定应激的mRNA。例如，在病毒感染期间维持抗病毒因子的表达。在这里，我们研究了由γ冠状病毒传染性支气管炎病毒（IBV）引起的应激颗粒调节，IBV引起经济上重要的家禽疾病，传染性支气管炎。有趣的是，我们发现IBV能够抑制多种细胞应激颗粒信号传导途径，同时IBV复制也导致在一定比例的感染细胞中诱导看似典型的应激颗粒。此外，IBV感染解除了翻译抑制和应激颗粒形成的偶联，并且这两个过程都不依赖于eIF2α磷酸化。这些结果为IBV如何调节细胞翻译和抗病毒应激信号提供了新的见解。
Viruses must hijack cellular translation machinery to efficiently express viral genes. In many cases, this is impeded by cellular stress responses. These stress responses swiftly relocate and repurpose translation machinery, resulting in global inhibition of translation and the aggregation of stalled 48S mRNPs into cytoplasmic foci called stress granules. This results in translational silencing of all mRNAs excluding those beneficial for the cell to resolve the specific stress. For example, expression of antiviral factors is maintained during viral infection. Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis virus (IBV), which causes the economically important poultry disease, infectious bronchitis. Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways whilst at the same time IBV replication also results in induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. These results provide novel insights into how IBV modulates cellular translation and antiviral stress signaling.