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Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV.
Stukalov, Alexey; Girault, Virginie; Grass, Vincent; Karayel, Ozge; Bergant, Valter; Urban, Christian; Haas, Darya A; Huang, Yiqi; Oubraham, Lila; Wang, Anqi; Hamad, M Sabri; Piras, Antonio; Hansen, Fynn M; Tanzer, Maria C; Paron, Igor; Zinzula, Luca; Engleitner, Thomas; Reinecke, Maria; Lavacca, Teresa M; Ehmann, Rosina; Wölfel, Roman; Jores, Jörg; Kuster, Bernhard; Protzer, Ulrike; Rad, Roland; Ziebuhr, John; Thiel, Volker; Scaturro, Pietro; Mann, Matthias; Pichlmair, Andreas.
Afiliação
  • Stukalov A; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Girault V; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Grass V; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Karayel O; Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
  • Bergant V; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Urban C; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Haas DA; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Huang Y; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Oubraham L; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Wang A; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Hamad MS; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Piras A; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Hansen FM; Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
  • Tanzer MC; Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
  • Paron I; Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
  • Zinzula L; Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, Martinsried, Germany.
  • Engleitner T; Institute of Molecular Oncology and Functional Genomics and Department of Medicine II, School of Medicine, Technical University of Munich, Munich, Germany.
  • Reinecke M; Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany.
  • Lavacca TM; German Cancer Consortium (DKTK), Munich Partner Site, Munich, Germany.
  • Ehmann R; German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Wölfel R; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
  • Jores J; Bundeswehr Institute of Microbiology, Munich, Germany.
  • Kuster B; German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany.
  • Protzer U; Bundeswehr Institute of Microbiology, Munich, Germany.
  • Rad R; German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany.
  • Ziebuhr J; Institute of Veterinary Bacteriology, Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.
  • Thiel V; Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany.
  • Scaturro P; German Cancer Consortium (DKTK), Munich Partner Site, Munich, Germany.
  • Mann M; German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Pichlmair A; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.
Nature ; 594(7862): 246-252, 2021 06.
Article em En | MEDLINE | ID: mdl-33845483
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-ß 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Síndrome Respiratória Aguda Grave / Proteômica / Coronavírus Relacionado à Síndrome Respiratória Aguda Grave / Interações Hospedeiro-Patógeno / SARS-CoV-2 / COVID-19 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Síndrome Respiratória Aguda Grave / Proteômica / Coronavírus Relacionado à Síndrome Respiratória Aguda Grave / Interações Hospedeiro-Patógeno / SARS-CoV-2 / COVID-19 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido