• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
【24h】

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

机译：多级蛋白质组学通过SARS-COV-2和SARS-COV显示宿主扰动

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology~(1-10). Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.
机译：SARS-COV-2的出现和全球传播导致了迫切需要深入了解病毒蛋白的分子功能及其与宿主蛋白质的相互作用。几项个体OMICS研究延长了我们对Covid-19病理生理学的了解〜（1-10）。这种数据集的整合以获得病毒 - 宿主相互作用的整体视图，并定义SARS-COV-2的致病性质受实验系统的异质性的限制。在这里，我们报告了SARS-COV-2和SARS-COV的并发多个OMICS研究。使用最先进的蛋白质组学，我们探讨了两种病毒的杂志，以及它们对转录组，蛋白质组，遍历蛋白酶和肺衍生的人细胞系的磷酸磷蛋白酶的影响。这些数据投影到细胞相互作用的全球网络发现发生在感染SARS-COV-2和SARS冠状病毒在不同层面并启用识别这些密切相关的冠状病毒不同，共同的分子机制的扰动之间的串扰。通过SARS-COV-2 ORF8特异性地描述了由SARS-COV-2 ORF8特异性测定的TGF-β途径，通过SARS-COV-2 ORF3特异性地测定自噬。广泛的数据集（可在https://covinet.innatelab.org上使用）突出了许多可以由现有药物定位的热点，并且可用于指导我们通过识别抑制剂来指导病毒和寄宿针对疗法的理性设计。激酶和基质金属蛋白酶对SARS-COV-2具有有效的抗病毒作用。

著录项

  • 来源
    《Nature》 |2021年第7862期|246-252|共7页
  • 作者

    Alexey Stukalov; Virginie Girault; Vincent Grass; Ozge Karayel; Valter Bergant; Christian Urban; Darya A Haas; Yiqi Huang; Lila Oubraham; Anqi Wang; M Sabri Hamad; Antonio Piras; Fynn M Hansen; Maria C Tanzer; Igor Paron; Luca Zinzula; Thomas Engleitner; Maria Reinecke; Teresa M Lavacca; Rosina Ehmann; Roman Wölfel; Jörg Jores; Bernhard Kuster; Ulrike Protzer; Roland Rad; John Ziebuhr; Volker Thiel; Pietro Scaturro; Matthias Mann; Andreas Pichlmair;

  • 作者单位

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Department of Proteomics and Signal Transduction Max-Planck Institute of Biochemistry;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Technical University of Munich School of Medicine Institute of Virology;

    Department of Proteomics and Signal Transduction Max-Planck Institute of Biochemistry;

    Department of Proteomics and Signal Transduction Max-Planck Institute of Biochemistry;

    Department of Proteomics and Signal Transduction Max-Planck Institute of Biochemistry;

    Department of Molecular Structural Biology Max-Planck Institute of Biochemistry;

    Institute of Molecular Oncology and Functional Genomics and Department of Medicine II School of Medicine Technical University of Munich;

    Technical University of Munich|German Cancer Consortium (DKTK) Munich Partner Site|German Cancer Research Center (DKFZ);

    Technical University of Munich School of Medicine Institute of Virology;

    Bundeswehr Institute of Microbiology|German Center for Infection Research (DZIF) Munich Partner Site;

    Bundeswehr Institute of Microbiology|German Center for Infection Research (DZIF) Munich Partner Site;

    Institute of Veterinary Bacteriology Department of Infectious Diseases and Pathobiology University of Bern;

    Technical University of Munich|German Cancer Consortium (DKTK) Munich Partner Site|German Cancer Research Center (DKFZ);

    Technical University of Munich School of Medicine Institute of Virology|German Center for Infection Research (DZIF) Munich Partner Site;

    Institute of Molecular Oncology and Functional Genomics and Department of Medicine II School of Medicine Technical University of Munich;

    Justus Liebig University Giessen Institute of Medical Virology;

    Institute of Virology and Immunology (IVI)|Department of Infectious Diseases and Pathobiology University of Bern;

    Technical University of Munich School of Medicine Institute of Virology|Leibniz Institute for Experimental Virology;

    Department of Proteomics and Signal Transduction Max-Planck Institute of Biochemistry;

    Technical University of Munich School of Medicine Institute of Virology|German Center for Infection Research (DZIF) Munich Partner Site;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号