受感染细胞的肖像：严重急性呼吸系统综合征冠状病毒2型感染如何重塑细胞过程和途径-动脉网

A portrait of the infected cell: how SARS-CoV-2 infection reshapes cellular processes and pathways

Nature 等信源发布 2024-12-17 22:46

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AbstractPositive-sense single-stranded RNA (+ssRNA) viruses exert a profound influence on cellular organelles and metabolic pathway by usurping host processes to promote their replication. In this review, we present a portrait of selected cellular pathways perturbed in SARS-CoV-2 infection: the effect of viral translation, replication and assembly on the morphology and function of the ER, the remodelling of degradative pathways with a focus on the autophagic processes, and the alterations affecting cellular membranes and lipid metabolism.

摘要正义单链RNA（+ssRNA）病毒通过篡夺宿主过程促进其复制，对细胞器和代谢途径产生深远影响。在这篇综述中，我们介绍了SARS-CoV-2感染中受干扰的选定细胞途径的肖像：病毒翻译，复制和组装对ER形态和功能的影响，降解途径的重塑，重点是自噬过程，以及影响细胞膜和脂质代谢的改变。

For each of these cellular processes, we highlight the specific viral and host factors involved and their interplay in this microscopic tug-of-war between pro-viral and anti-viral effects that ultimately tip the scale toward the propagation or the resolution of the infection..

对于这些细胞过程中的每一个，我们都强调了所涉及的特定病毒和宿主因素及其在促病毒和抗病毒作用之间的微观拔河中的相互作用，最终将规模推向传播或解决感染。。

IntroductionSARS-CoV-2, the aetiological agent of the fast evolving COVID-19 pandemic, belongs to the group of β-coronaviruses within the Coronaviridae family (order Nidovirales) of +ssRNA viruses1,2. After viral entry mediated by the ACE-2 receptor, SARS-CoV-2 positive-sense RNA genome is directly translated into the large ORF1a and ORF1ab polyproteins, which are then cleaved in a total of 16 non-structural proteins (NSPs).

引言SARS-CoV-2是快速发展的COVID-19大流行的病原体，属于+ssRNA病毒的冠状病毒科（Nidovirales）中的β-冠状病毒组1,2。在ACE-2受体介导的病毒进入后，SARS-CoV-2阳性RNA基因组直接翻译成大的ORF1a和ORF1ab多蛋白，然后将其切割成总共16种非结构蛋白（NSP）。

The NSPs assemble to form the replication and transcription complex (RTC), containing the RNA-dependent RNA polymerase (RdRp), responsible for the transcription of subgenomic and genomic viral RNA. After the interaction between the newly synthesized genomic RNA and the Nucleocapsid (N) protein, new virions assemble at the ER—Golgi intermediate compartment (ERGIC) and are released through either the conventional secretory pathway or by exocytic lysosomes via multivesicular bodies (MVBs) (Fig.

NSP组装形成复制和转录复合物（RTC），包含RNA依赖性RNA聚合酶（RdRp），负责亚基因组和基因组病毒RNA的转录。在新合成的基因组RNA和核衣壳（N）蛋白之间的相互作用后，新的病毒粒子在ER-高尔基体中间区室（ERGIC）组装，并通过常规分泌途径或通过多囊泡体（MVB）的胞外溶酶体释放（图）。

1)3. Similarly to other +ssRNA viruses, genome replication occurs within the cytosol of the infected cells. However, the cytoplasm represents a hostile environment due to the presence of the innate immune sensors able to detect the viral RNA and the double-stranded RNA (dsRNA) replication intermediate.

1）三。与其他+ssRNA病毒类似，基因组复制发生在感染细胞的胞质溶胶内。然而，由于存在能够检测病毒RNA和双链RNA（dsRNA）复制中间体的先天免疫传感器，细胞质代表了一种恶劣的环境。

To protect the dsRNA from the host immune sensing, +ssRNA genome replication occurs within specialised, virus-induced membrane-delimited compartments called viral replication organelles (vROs). The compartmentalisation and RNA replication step within the vROs brings several advantages: (i) the dsRNA present within the vROs interior cannot be reached by the cytosolic host immune sensors, (ii) the membrane-delimited environment allows to achieve higher local concentration of metabolites and factors required for RNA synthesis, and (iii) the separation between the rep.

为了保护dsRNA免受宿主免疫感应，+ssRNA基因组复制发生在称为病毒复制细胞器（VRO）的专门的，病毒诱导的膜分隔区室内。vROs内的区室化和RNA复制步骤带来了几个优点：（i）存在于vROs内部的dsRNA不能被胞质宿主免疫传感器达到，（ii）膜分隔的环境允许实现更高的局部代谢物浓度和RNA合成所需的因子，以及（iii）rep之间的分离。

Data availability

数据可用性

No datasets were generated or analysed during the current study.

在当前的研究中，没有生成或分析数据集。

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Download referencesAcknowledgementsAll the figures in this review were generated with Biorender. MC is supported by the Human Technopole Early Career Fellowship Programme (HT-ECF 763 Programme). SMLT and ŠV are supported by a PhD Fellowship from the Scuola Superiore Meridionale (SSM).Author informationAuthor notesThese authors contributed equally: Valentina Marano, Štěpánka Vlachová, Sofia Maria Luigia Tiano.Authors and AffiliationsTelethon Institute of Genetics and Medicine, Pozzuoli, ItalyValentina Marano, Štěpánka Vlachová, Sofia Maria Luigia Tiano & Mirko CorteseUniversity of Rome Tor Vergata, Rome, ItalyValentina MaranoScuola Superiore Meridionale, Naples, ItalyŠtěpánka Vlachová & Sofia Maria Luigia TianoUniversity of Campania Luigi Vanvitelli, Caserta, ItalyMirko CorteseAuthorsValentina MaranoView author publicationsYou can also search for this author in.

下载参考文献致谢本评价中的所有数字均由Biorender生成。MC得到了人类技术极早期职业奖学金计划（HT-ECF 763计划）的支持。SMLT和ŠV得到了Scuola Superiore Meridionale（SSM）的博士奖学金的支持。作者信息作者注意到这些作者做出了同样的贡献：瓦伦蒂娜·马拉诺，什蒂安·潘卡·弗拉乔娃，索菲亚·玛丽亚·路易贾·蒂亚诺。作者和附属机构意大利瓦伦蒂娜·马拉诺，波佐利，意大利瓦伦蒂娜·马拉诺，什切帕斯卡·弗拉乔娃，索菲亚·玛利亚·路易贾·蒂亚诺和米尔科·科尔特斯大学，罗马托尔加塔，意大利那不勒斯，意大利瓦伦蒂娜·马拉诺斯科拉高级梅里迪奥纳勒，意大利瓦伦蒂娜·弗拉乔娃和索菲亚·玛利亚·路易贾·蒂亚诺坎帕尼亚大学路易吉·瓦维泰利分校，卡塞塔，意大利瓦伦蒂娜·科尔特斯作家瓦伦蒂娜·马拉诺维作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsVM, SMLT, ŠV and MC wrote and reviewed the manuscript. VM, SMLT and ŠV prepared the figures and share equal contribution. All authors have read and approved the manuscript.Corresponding authorCorrespondence to

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Reprints and permissionsAbout this articleCite this articleMarano, V., Vlachová, Š., Tiano, S.M.L. et al. A portrait of the infected cell: how SARS-CoV-2 infection reshapes cellular processes and pathways.

转载和许可本文引用本文Marano，V.，Vlachová，Š。，Tiano，S.M.L.等人，《感染细胞的肖像：SARS-CoV-2感染如何重塑细胞过程和途径》。

npj Viruses 2, 66 (2024). https://doi.org/10.1038/s44298-024-00076-8Download citationReceived: 10 September 2024Accepted: 22 November 2024Published: 17 December 2024DOI: https://doi.org/10.1038/s44298-024-00076-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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