SARS-CoV-2 infection remodels the host protein thermal stability landscape.
SARS-CoV-2
aryl hydrocarbon hydroxylase
heat shock chaperone
rhapontigenin
tanespimycin
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
21
12
2020
revised:
15
01
2021
accepted:
18
01
2021
entrez:
16
2
2021
pubmed:
17
2
2021
medline:
20
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33590968
doi: 10.15252/msb.202010188
pmc: PMC7885171
doi:
Substances chimiques
Antiviral Agents
0
Proteome
0
Viral Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e10188Subventions
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : 819454
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 240245660
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 278001972
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 415089553
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 272983813
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 416072091
Organisme : Bundesministerium für Bildung und Forschung (BMBF)
ID : 01KI20198A
Organisme : German Center for Infection Research (DZIF)
ID : 8029801806
Organisme : German Center for Infection Research (DZIF)
ID : 8029705705
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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