《BioRxiv,3月24日,A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangmin
  • 发布时间:2020-03-25
  • A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis

    Eric J. Snijder, Ronald W.A.L. Limpens, Adriaan H. de Wilde, Anja W. M. de Jong, Jessika C. Zevenhoven-Dobbe, Helena J. Maier, F.G.A. Faas, Abraham J. Koster, View ORCID ProfileMontserrat Bárcena

    doi: https://doi.org/10.1101/2020.03.24.005298

    Abstract

    Zoonotic coronavirus (CoV) infections, like those responsible for the current SARS-CoV-2 epidemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). While double-membrane vesicles (DMVs) appear to be a pan -coronavirus RO element, studies to date describe an assortment of additional coronavirus-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication.

    *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用.

  • 原文来源:https://www.biorxiv.org/content/10.1101/2020.03.24.005298v1
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    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-08-18
    • A molecular pore spans the double membrane of the coronavirus replication organelle View ORCID ProfileGeorg Wolff1, View ORCID ProfileRonald W. A. L. Limpens1, Jessika C. Zevenhoven-Dobbe2, View ORCID ProfileUlrike Laugks3, View ORCID ProfileShawn Zheng4, View ORCID ProfileAnja W. M. de Jong1, View ORCID ProfileRoman I. Koning1, View ORCID ProfileDavid A. Agard5, View ORCID ProfileKay Grünewald3,6, View ORCID ProfileAbraham J. Koster1, View ORCID ProfileEric J. Snijder2, View ORCID ProfileMontserrat Bárcena1,* See all authors and affiliations Science  06 Aug 2020: eabd3629 DOI: 10.1126/science.abd3629 Abstract Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored micro-environment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and mRNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. Here, we used cellular electron cryo-microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a critical role in coronavirus replication and thus constitutes a potential drug target.
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    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-03-26
    • 1.时间:2020年3月24日 2.机构或团队:莱顿大学、英国皮尔布莱特研究所 3.事件概要: 3月24日,bioRxiv预印本平台发表了来自莱顿大学,英国皮尔布莱特研究所研究团队的题为“A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis”的文章。 该文章指出,人畜共患型冠状病毒(CoV)感染引起了国际社会的关注。在被感染的细胞中,冠状病毒(CoV)RNA合成机制与修饰的内质网膜结合,这些内质网膜被转化为病毒复制细胞器(RO)。虽然双膜囊泡(DMV)似乎是泛冠状病毒RO元件,但迄今为止的研究描述了各种其他冠状病毒诱导的膜结构。尽管有很多猜测,但尚不清楚哪些RO元件可调节病毒RNA的合成。该文章提供了冠状病毒RO的详细2D和3D分析,并显示了不同的冠状病毒本质上会引起相同的膜修饰,包括以前被认为只限于γ-CoV和δ-CoV感染的小型打开的双膜小球(DMS),并被建议作为复制位点。对新合成的病毒RNA进行代谢标记,然后进行定量EM放射自显影,发现在被β-CoV MERS-CoV和SARS-CoV以及γ-CoV病毒感染的细胞中,与DMV相关的大量病毒RNA合成。RNA合成不能与DMS或任何其他细胞或病毒诱导的结构相连。该文章认为,其提供了冠状病毒RO的统一模型,并清楚地将DMV建立为病毒RNA合成的中心枢纽和冠状病毒感染的潜在药物靶标。 *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用。 4.附件: 原文链接https://www.biorxiv.org/content/10.1101/2020.03.24.005298v1