IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v594y2021i7862d10.1038_s41586-021-03493-4.html
   My bibliography  Save this article

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

Author

Listed:
  • Alexey Stukalov

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Virginie Girault

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Vincent Grass

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Ozge Karayel

    (Max-Planck Institute of Biochemistry)

  • Valter Bergant

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Christian Urban

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Darya A. Haas

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Yiqi Huang

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Lila Oubraham

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Anqi Wang

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • M. Sabri Hamad

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Antonio Piras

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Fynn M. Hansen

    (Max-Planck Institute of Biochemistry)

  • Maria C. Tanzer

    (Max-Planck Institute of Biochemistry)

  • Igor Paron

    (Max-Planck Institute of Biochemistry)

  • Luca Zinzula

    (Max-Planck Institute of Biochemistry)

  • Thomas Engleitner

    (Technical University of Munich)

  • Maria Reinecke

    (Technical University of Munich
    Munich Partner Site
    German Cancer Research Center (DKFZ))

  • Teresa M. Lavacca

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Rosina Ehmann

    (Bundeswehr Institute of Microbiology
    Munich Partner Site)

  • Roman Wölfel

    (Bundeswehr Institute of Microbiology
    Munich Partner Site)

  • Jörg Jores

    (University of Bern)

  • Bernhard Kuster

    (Technical University of Munich
    Munich Partner Site
    German Cancer Research Center (DKFZ))

  • Ulrike Protzer

    (Technical University of Munich, School of Medicine, Institute of Virology
    Munich Partner Site)

  • Roland Rad

    (Technical University of Munich)

  • John Ziebuhr

    (Justus Liebig University Giessen, Institute of Medical Virology)

  • Volker Thiel

    (Institute of Virology and Immunology (IVI)
    University of Bern)

  • Pietro Scaturro

    (Technical University of Munich, School of Medicine, Institute of Virology
    Leibniz Institute for Experimental Virology)

  • Matthias Mann

    (Max-Planck Institute of Biochemistry)

  • Andreas Pichlmair

    (Technical University of Munich, School of Medicine, Institute of Virology
    Munich Partner Site)

Abstract

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 pathophysiology1–10. 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.

Suggested Citation

  • 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., 2021. "Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV," Nature, Nature, vol. 594(7862), pages 246-252, June.
  • Handle: RePEc:nat:nature:v:594:y:2021:i:7862:d:10.1038_s41586-021-03493-4
    DOI: 10.1038/s41586-021-03493-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03493-4
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-03493-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yiqi Huang & Valter Bergant & Vincent Grass & Quirin Emslander & M. Sabri Hamad & Philipp Hubel & Julia Mergner & Antonio Piras & Karsten Krey & Alexander Henrici & Rupert Öllinger & Yonas M. Tesfamar, 2024. "Multi-omics characterization of the monkeypox virus infection," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Sara Sunshine & Andreas S. Puschnik & Joseph M. Replogle & Matthew T. Laurie & Jamin Liu & Beth Shoshana Zha & James K. Nuñez & Janie R. Byrum & Aidan H. McMorrow & Matthew B. Frieman & Juliane Winkle, 2023. "Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Andrea Fossati & Deepto Mozumdar & Claire Kokontis & Melissa Mèndez-Moran & Eliza Nieweglowska & Adrian Pelin & Yuping Li & Baron Guo & Nevan J. Krogan & David A. Agard & Joseph Bondy-Denomy & Daniell, 2023. "Next-generation proteomics for quantitative Jumbophage-bacteria interaction mapping," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Debjit Khan & Fulvia Terenzi & GuanQun Liu & Prabar K. Ghosh & Fengchun Ye & Kien Nguyen & Arnab China & Iyappan Ramachandiran & Shruti Chakraborty & Jennifer Stefan & Krishnendu Khan & Kommireddy Vas, 2023. "A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Solène Denolly & Alexey Stukalov & Uladzimir Barayeu & Alina N. Rosinski & Paraskevi Kritsiligkou & Sebastian Joecks & Tobias P. Dick & Andreas Pichlmair & Ralf Bartenschlager, 2023. "Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Friederike L. Pennemann & Assel Mussabekova & Christian Urban & Alexey Stukalov & Line Lykke Andersen & Vincent Grass & Teresa Maria Lavacca & Cathleen Holze & Lila Oubraham & Yasmine Benamrouche & En, 2021. "Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    7. Thomas Kruse & Caroline Benz & Dimitriya H. Garvanska & Richard Lindqvist & Filip Mihalic & Fabian Coscia & Raviteja Inturi & Ahmed Sayadi & Leandro Simonetti & Emma Nilsson & Muhammad Ali & Johanna K, 2021. "Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    8. Filip Mihalič & Caroline Benz & Eszter Kassa & Richard Lindqvist & Leandro Simonetti & Raviteja Inturi & Hanna Aronsson & Eva Andersson & Celestine N. Chi & Norman E. Davey & Anna K. Överby & Per Jemt, 2023. "Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Haris Babačić & Wanda Christ & José Eduardo Araújo & Georgios Mermelekas & Nidhi Sharma & Janne Tynell & Marina García & Renata Varnaite & Hilmir Asgeirsson & Hedvig Glans & Janne Lehtiö & Sara Gredma, 2023. "Comprehensive proteomics and meta-analysis of COVID-19 host response," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Ma’ayan Israeli & Yaara Finkel & Yfat Yahalom-Ronen & Nir Paran & Theodor Chitlaru & Ofir Israeli & Inbar Cohen-Gihon & Moshe Aftalion & Reut Falach & Shahar Rotem & Uri Elia & Ital Nemet & Limor Klik, 2022. "Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. Valter Bergant & Daniel Schnepf & Niklas Andrade Krätzig & Philipp Hubel & Christian Urban & Thomas Engleitner & Ronald Dijkman & Bernhard Ryffel & Katja Steiger & Percy A. Knolle & Georg Kochs & Rola, 2023. "mRNA 3’UTR lengthening by alternative polyadenylation attenuates inflammatory responses and correlates with virulence of Influenza A virus," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Gianluca Baldanzi & Beatrice Purghè & Beatrice Ragnoli & Pier Paolo Sainaghi & Roberta Rolla & Annalisa Chiocchetti & Marcello Manfredi & Mario Malerba, 2023. "Circulating Peptidome Is Strongly Altered in COVID-19 Patients," IJERPH, MDPI, vol. 20(2), pages 1-15, January.
    13. Emilie Murigneux & Laurent Softic & Corentin Aubé & Carmen Grandi & Delphine Judith & Johanna Bruce & Morgane Le Gall & François Guillonneau & Alain Schmitt & Vincent Parissi & Clarisse Berlioz-Torren, 2024. "Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:594:y:2021:i:7862:d:10.1038_s41586-021-03493-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.