SARS‐CoV‐2 infection remodels the host protein thermal stability landscape
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‐wid...
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Springer Nature
2021-02-01
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Series: | Molecular Systems Biology |
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Online Access: | https://doi.org/10.15252/msb.202010188 |
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author | Joel Selkrig Megan Stanifer André Mateus Karin Mitosch Inigo Barrio‐Hernandez Mandy Rettel Heeyoung Kim Carlos G P Voogdt Philipp Walch Carmon Kee Nils Kurzawa Frank Stein Clément Potel Anna Jarzab Bernhard Kuster Ralf Bartenschlager Steeve Boulant Pedro Beltrao Athanasios Typas Mikhail M Savitski |
author_facet | Joel Selkrig Megan Stanifer André Mateus Karin Mitosch Inigo Barrio‐Hernandez Mandy Rettel Heeyoung Kim Carlos G P Voogdt Philipp Walch Carmon Kee Nils Kurzawa Frank Stein Clément Potel Anna Jarzab Bernhard Kuster Ralf Bartenschlager Steeve Boulant Pedro Beltrao Athanasios Typas Mikhail M Savitski |
author_sort | Joel Selkrig |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-07T17:06:10Z |
format | Article |
id | doaj.art-afece9f0c9684154826067b58f6e27a7 |
institution | Directory Open Access Journal |
issn | 1744-4292 |
language | English |
last_indexed | 2025-02-18T14:13:47Z |
publishDate | 2021-02-01 |
publisher | Springer Nature |
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series | Molecular Systems Biology |
spelling | doaj.art-afece9f0c9684154826067b58f6e27a72024-10-28T09:22:39ZengSpringer NatureMolecular Systems Biology1744-42922021-02-0117211310.15252/msb.202010188SARS‐CoV‐2 infection remodels the host protein thermal stability landscapeJoel Selkrig0Megan Stanifer1André Mateus2Karin Mitosch3Inigo Barrio‐Hernandez4Mandy Rettel5Heeyoung Kim6Carlos G P Voogdt7Philipp Walch8Carmon Kee9Nils Kurzawa10Frank Stein11Clément Potel12Anna Jarzab13Bernhard Kuster14Ralf Bartenschlager15Steeve Boulant16Pedro Beltrao17Athanasios Typas18Mikhail M Savitski19Genome Biology Unit, European Molecular Biology Laboratory (EMBL)Department of Infectious Diseases, Molecular Virology, Heidelberg University HospitalGenome Biology Unit, European Molecular Biology Laboratory (EMBL)Genome Biology Unit, European Molecular Biology Laboratory (EMBL)European Bioinformatics Institute (EMBL‐EBI)Proteomics Core Facility, European Molecular Biology Laboratory (EMBL)Department of Infectious Diseases, Molecular Virology, Heidelberg University HospitalGenome Biology Unit, European Molecular Biology Laboratory (EMBL)Genome Biology Unit, European Molecular Biology Laboratory (EMBL)Department of Infectious Diseases, Molecular Virology, Heidelberg University HospitalGenome Biology Unit, European Molecular Biology Laboratory (EMBL)Proteomics Core Facility, European Molecular Biology Laboratory (EMBL)Genome Biology Unit, European Molecular Biology Laboratory (EMBL)Proteomics and Bioanalytics, Technical University of MunichProteomics and Bioanalytics, Technical University of MunichDepartment of Infectious Diseases, Molecular Virology, Heidelberg University HospitalDepartment of Infectious Diseases, Virology, Heidelberg University HospitalEuropean Bioinformatics Institute (EMBL‐EBI)Genome Biology Unit, European Molecular Biology Laboratory (EMBL)Genome Biology Unit, European Molecular Biology Laboratory (EMBL)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.https://doi.org/10.15252/msb.202010188aryl hydrocarbon hydroxylaseheat shock chaperonerhapontigeninSARS‐CoV‐2tanespimycin |
spellingShingle | Joel Selkrig Megan Stanifer André Mateus Karin Mitosch Inigo Barrio‐Hernandez Mandy Rettel Heeyoung Kim Carlos G P Voogdt Philipp Walch Carmon Kee Nils Kurzawa Frank Stein Clément Potel Anna Jarzab Bernhard Kuster Ralf Bartenschlager Steeve Boulant Pedro Beltrao Athanasios Typas Mikhail M Savitski SARS‐CoV‐2 infection remodels the host protein thermal stability landscape Molecular Systems Biology aryl hydrocarbon hydroxylase heat shock chaperone rhapontigenin SARS‐CoV‐2 tanespimycin |
title | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_full | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_fullStr | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_full_unstemmed | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_short | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_sort | sars cov 2 infection remodels the host protein thermal stability landscape |
topic | aryl hydrocarbon hydroxylase heat shock chaperone rhapontigenin SARS‐CoV‐2 tanespimycin |
url | https://doi.org/10.15252/msb.202010188 |
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