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正链 RNA 病毒基因组复制复合物结构与功能的点睛之笔

Crowning Touches in Positive-Strand RNA Virus Genome Replication Complex Structure and Function.

机构信息

John and Jeanne Rowe Center for Research in Virology, Morgridge Institute for Research, Madison, Wisconsin, USA; email:

Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.

出版信息

Annu Rev Virol. 2022 Sep 29;9(1):193-212. doi: 10.1146/annurev-virology-092920-021307. Epub 2022 May 24.

Abstract

Positive-strand RNA viruses, the largest genetic class of eukaryotic viruses, include coronaviruses and many other established and emerging pathogens. A major target for understanding and controlling these viruses is their genome replication, which occurs in virus-induced membrane vesicles that organize replication steps and protect double-stranded RNA intermediates from innate immune recognition. The structure of these complexes has been greatly illuminated by recent cryo-electron microscope tomography studies with several viruses. One key finding in diverse systems is the organization of crucial viral RNA replication factors in multimeric rings or crowns that among other functions serve as exit channels gating release of progeny genomes to the cytosol for translation and encapsidation. Emerging results suggest that these crowns serve additional important purposes in replication complex assembly, function, and interaction with downstream processes such as encapsidation. The findings provide insights into viral function and evolution and new bases for understanding, controlling, and engineering positive-strand RNA viruses.

摘要

正链 RNA 病毒是真核病毒中最大的遗传类群,包括冠状病毒和许多其他已确定和新出现的病原体。了解和控制这些病毒的主要目标是它们的基因组复制,该过程发生在病毒诱导的膜泡中,这些膜泡组织复制步骤并保护双链 RNA 中间体免受先天免疫识别。最近对几种病毒进行的低温电子显微镜断层扫描研究极大地阐明了这些复合物的结构。在不同系统中一个关键发现是关键病毒 RNA 复制因子以多聚体环或冠状的形式组织,除了其他功能外,这些环或冠状作为出口通道,控制新生基因组释放到细胞质中进行翻译和包装。新出现的结果表明,这些冠状结构在复制复合物组装、功能以及与下游过程(如包装)的相互作用中具有额外的重要作用。这些发现为理解、控制和工程化正链 RNA 病毒提供了病毒功能和进化的新见解和基础。

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