2. Academic Validation
  3. SARS-CoV-2 infection remodels the host protein thermal stability landscape

SARS-CoV-2 infection remodels the host protein thermal stability landscape

  • Mol Syst Biol. 2021 Feb;17(2):e10188. doi: 10.15252/msb.202010188.
Joel Selkrig 1,  Megan Stanifer 2,  André Mateus 1,  Karin Mitosch 1,  Inigo Barrio-Hernandez 3,  Mandy Rettel 4,  Heeyoung Kim 2,  Carlos G P Voogdt 1,  Philipp Walch 1 5,  Carmon Kee 2,  Nils Kurzawa 1 5,  Frank Stein 4,  Clément Potel 1,  Anna Jarzab 6,  Bernhard Kuster 6,  Ralf Bartenschlager 2 7 8,  Steeve Boulant 9 10,  Pedro Beltrao 3,  Athanasios Typas 1,  Mikhail M Savitski 1
Affiliations

Affiliations

  • 1 Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
  • 2 Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany.
  • 3 European Bioinformatics Institute (EMBL-EBI), Hinxton, UK.
  • 4 Proteomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
  • 5 Faculty of Biosciences, EMBL and Heidelberg University, Heidelberg, Germany.
  • 6 Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany.
  • 7 Division "Virus-associated Carcinogenesis", German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 8 German Center for Infection Research, Heidelberg Partner site, Heidelberg, Germany.
  • 9 Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
  • 10 Research Group "Cellular Polarity and Viral Infection", German Cancer Research Center (DKFZ), Heidelberg, Germany.
PMID: 33590968 DOI: 10.15252/msb.202010188
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS-CoV-2 hijacks host cellular machineries on a system-wide scale so that potential host-directed therapies can be developed. In situ proteome-wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS-CoV-2 handling. We discovered pronounced temporal alterations in host protein thermostability during Infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during Infection suppressed SARS-CoV-2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS-CoV-2 Infection.

Keywords

SARS-CoV-2; aryl hydrocarbon hydroxylase; heat shock chaperone; rhapontigenin; tanespimycin.

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