A Mechanism for Priming and Realignment during Influenza A Virus Replication.
A Mechanism for Priming and Realignment during Influenza A Virus Replication.
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在流感A中启动和重新调整的一种病毒复制的机制。
DOI：
10.1128/jvi.01773-17
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发表时间：
2018-02-01
影响因子：
5.4
通讯作者：
Te Velthuis AJW
中科院分区：
文献类型：
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作者：
Oymans J;Te Velthuis AJW
甲型流感病毒基因组由八个单链RNA片段组成。这些片段通过由流感病毒蛋白PB1、PB2和PA组成的病毒RNA依赖性RNA聚合酶（RdRp）复制和转录。为了复制病毒RNA（vRNA）基因组片段和cRNA片段（病毒复制的复制中间体），RdRp必须使用两个启动子和两种不同的从头起始机制。在vRNA启动子上，RdRp起始于3′端，而在cRNA启动子上，RdRp在内部起始，随后重新排列新生的vRNA产物，以确保模板完全复制。特别是，后一个过程，这也是其他RNA病毒使用的，还不清楚。在这里，我们提供了在流感病毒复制过程中引发和重新排列的机制的见解，并表明它是由引发环和螺旋环螺旋基序的RdRp的PB1亚基控制。总的来说，这些观察结果推进了我们对甲型流感病毒如何启动病毒复制并正确扩增基因组的理解。重要性甲型流感病毒会导致人类严重疾病，被认为是对我们经济和健康的主要威胁。病毒通过使用一种称为RNA聚合酶的酶复制和转录它们的基因组。为了确保基因组被忠实地扩增，并为病毒蛋白质合成制造大量的病毒mRNA，RNA聚合酶必须正确地工作。在这份报告中，我们提供了深入了解的机制，RNA聚合酶采用，以确保病毒基因组被正确复制。
The influenza A virus genome consists of eight segments of single-stranded RNA. These segments are replicated and transcribed by a viral RNA-dependent RNA polymerase (RdRp) that is made up of the influenza virus proteins PB1, PB2, and PA. To copy the viral RNA (vRNA) genome segments and the cRNA segments, the replicative intermediate of viral replication, the RdRp must use two promoters and two different de novo initiation mechanisms. On the vRNA promoter, the RdRp initiates on the 3′ terminus, while on the cRNA promoter, the RdRp initiates internally and subsequently realigns the nascent vRNA product to ensure that the template is copied in full. In particular, the latter process, which is also used by other RNA viruses, is not understood. Here we provide mechanistic insight into priming and realignment during influenza virus replication and show that it is controlled by the priming loop and a helix-loop-helix motif of the PB1 subunit of the RdRp. Overall, these observations advance our understanding of how the influenza A virus initiates viral replication and amplifies the genome correctly. IMPORTANCE Influenza A viruses cause severe disease in humans and are considered a major threat to our economy and health. The viruses replicate and transcribe their genome by using an enzyme called the RNA polymerases. To ensure that the genome is amplified faithfully and that abundant viral mRNAs are made for viral protein synthesis, the RNA polymerase must work correctly. In this report, we provide insight into the mechanism that the RNA polymerase employs to ensure that the viral genome is copied correctly.