Abstract：
Viruses have evolved a range of strategies to utilize or manipulate the host\'s cellular translational machinery for efficient infection, although the mechanisms by which infectious bronchitis virus (IBV) manipulates the host translation machinery remain unclear. In this study, we firstly demonstrate that IBV infection causes host shutoff, although viral protein synthesis is not affected. We then screened 23 viral proteins, and identified that more than one viral protein is responsible for IBV-induced host shutoff, the inhibitory effects of proteins Nsp15 were particularly pronounced. Ribosome profiling was used to draw the landscape of viral mRNA and cellular genes expression model, and the results showed that IBV mRNAs gradually dominated the cellular mRNA pool, the translation efficiency of the viral mRNAs was lower than the median efficiency (about 1) of cellular mRNAs. In the analysis of viral transcription and translation, higher densities of RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) reads were observed for structural proteins and 5\' untranslated regions, which conformed to the typical transcriptional characteristics of nested viruses. Translational halt events and the number of host genes increased significantly after viral infection. The translationally paused genes were enriched in translation, unfolded-protein-related response, and activation of immune response pathways. Immune- and inflammation-related mRNAs were inefficiently translated in infected cells, and IBV infection delayed the production of IFN-β and IFN-λ. Our results describe the translational landscape of IBV-infected cells and demonstrate new strategies by which IBV induces host gene shutoff to promote its replication.
OBJECTIVE: Infectious bronchitis virus (IBV) is a γ-coronavirus that causes huge economic losses to the poultry industry. Understanding how the virus manipulates cellular biological processes to facilitate its replication is critical for controlling viral infections. Here, we used Ribo-seq to determine how IBV infection remodels the host\'s biological processes and identified multiple viral proteins involved in host gene shutoff. Immune- and inflammation-related mRNAs were inefficiently translated, the translation halt of unfolded proteins and immune activation-related genes increased significantly, benefitting IBV replication. These data provide new insights into how IBV modulates its host\'s antiviral responses.
OBJECTIVE: Infectious bronchitis virus (IBV) is a γ-coronavirus that causes huge economic losses to the poultry industry. Understanding how the virus manipulates cellular biological processes to facilitate its replication is critical for controlling viral infections. Here, we used Ribo-seq to determine how IBV infection remodels the host\'s biological processes and identified multiple viral proteins involved in host gene shutoff. Immune- and inflammation-related mRNAs were inefficiently translated, the translation halt of unfolded proteins and immune activation-related genes increased significantly, benefitting IBV replication. These data provide new insights into how IBV modulates its host\'s antiviral responses.
摘要：
病毒已经进化出一系列策略来利用或操纵宿主的细胞翻译机制进行有效感染，尽管传染性支气管炎病毒（IBV）操纵宿主翻译机制的机制尚不清楚。在这项研究中,我们首先证明IBV感染会导致宿主关闭，虽然病毒蛋白合成不受影响。然后我们筛选了23种病毒蛋白，并确定不止一种病毒蛋白负责IBV诱导的宿主关闭，蛋白质Nsp15的抑制作用特别明显。核糖体谱分析用于绘制病毒mRNA和细胞基因表达模型的景观，结果表明，IBVmRNA逐渐占据细胞mRNA库，病毒mRNA的翻译效率低于细胞mRNA的中位效率（约1）。在病毒转录和翻译的分析中，更高密度的RNA测序（RNA-seq）和核糖体分析（Ribo-seq）读数观察到结构蛋白和5个非翻译区，这符合巢式病毒的典型转录特征。病毒感染后，翻译停止事件和宿主基因数量显着增加。翻译暂停的基因在翻译中丰富，未折叠的蛋白质相关反应，和免疫应答途径的激活。免疫和炎症相关的mRNA在感染的细胞中翻译效率低下，和IBV感染延迟了IFN-β和IFN-λ的产生。我们的结果描述了IBV感染细胞的翻译景观，并展示了IBV诱导宿主基因关闭以促进其复制的新策略。
目的：传染性支气管炎病毒（IBV）是一种γ-冠状病毒，给家禽业造成巨大的经济损失。了解病毒如何操纵细胞生物过程以促进其复制对于控制病毒感染至关重要。这里,我们使用Ribo-seq来确定IBV感染如何重塑宿主的生物学过程,并鉴定了参与宿主基因关闭的多种病毒蛋白.免疫和炎症相关的mRNA翻译效率低下，未折叠蛋白和免疫激活相关基因的翻译停止显著增加，有利于IBV复制。这些数据为IBV如何调节其宿主的抗病毒反应提供了新的见解。
目的：传染性支气管炎病毒（IBV）是一种γ-冠状病毒，给家禽业造成巨大的经济损失。了解病毒如何操纵细胞生物过程以促进其复制对于控制病毒感染至关重要。这里,我们使用Ribo-seq来确定IBV感染如何重塑宿主的生物学过程,并鉴定了参与宿主基因关闭的多种病毒蛋白.免疫和炎症相关的mRNA翻译效率低下，未折叠蛋白和免疫激活相关基因的翻译停止显著增加，有利于IBV复制。这些数据为IBV如何调节其宿主的抗病毒反应提供了新的见解。
