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

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 s...

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Autores principales: Selkrig, Joel, Stanifer, Megan, Mateus, André, Mitosch, Karin, Barrio‐Hernandez, Inigo, Rettel, Mandy, Kim, Heeyoung, Voogdt, Carlos G P, Walch, Philipp, Kee, Carmon, Kurzawa, Nils, Stein, Frank, Potel, Clément, Jarzab, Anna, Kuster, Bernhard, Bartenschlager, Ralf, Boulant, Steeve, Beltrao, Pedro, Typas, Athanasios, Savitski, Mikhail M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885171/
https://www.ncbi.nlm.nih.gov/pubmed/33590968
http://dx.doi.org/10.15252/msb.202010188
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author Selkrig, Joel
Stanifer, Megan
Mateus, André
Mitosch, Karin
Barrio‐Hernandez, Inigo
Rettel, Mandy
Kim, Heeyoung
Voogdt, Carlos G P
Walch, Philipp
Kee, Carmon
Kurzawa, Nils
Stein, Frank
Potel, Clément
Jarzab, Anna
Kuster, Bernhard
Bartenschlager, Ralf
Boulant, Steeve
Beltrao, Pedro
Typas, Athanasios
Savitski, Mikhail M
author_facet Selkrig, Joel
Stanifer, Megan
Mateus, André
Mitosch, Karin
Barrio‐Hernandez, Inigo
Rettel, Mandy
Kim, Heeyoung
Voogdt, Carlos G P
Walch, Philipp
Kee, Carmon
Kurzawa, Nils
Stein, Frank
Potel, Clément
Jarzab, Anna
Kuster, Bernhard
Bartenschlager, Ralf
Boulant, Steeve
Beltrao, Pedro
Typas, Athanasios
Savitski, Mikhail M
author_sort Selkrig, Joel
collection PubMed
description 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.
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spelling pubmed-78851712021-02-26 SARS‐CoV‐2 infection remodels the host protein thermal stability landscape Selkrig, Joel Stanifer, Megan Mateus, André Mitosch, Karin Barrio‐Hernandez, Inigo Rettel, Mandy Kim, Heeyoung Voogdt, Carlos G P Walch, Philipp Kee, Carmon Kurzawa, Nils Stein, Frank Potel, Clément Jarzab, Anna Kuster, Bernhard Bartenschlager, Ralf Boulant, Steeve Beltrao, Pedro Typas, Athanasios Savitski, Mikhail M Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2021-02-16 /pmc/articles/PMC7885171/ /pubmed/33590968 http://dx.doi.org/10.15252/msb.202010188 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Selkrig, Joel
Stanifer, Megan
Mateus, André
Mitosch, Karin
Barrio‐Hernandez, Inigo
Rettel, Mandy
Kim, Heeyoung
Voogdt, Carlos G P
Walch, Philipp
Kee, Carmon
Kurzawa, Nils
Stein, Frank
Potel, Clément
Jarzab, Anna
Kuster, Bernhard
Bartenschlager, Ralf
Boulant, Steeve
Beltrao, Pedro
Typas, Athanasios
Savitski, Mikhail M
SARS‐CoV‐2 infection remodels the host protein thermal stability landscape
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 Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885171/
https://www.ncbi.nlm.nih.gov/pubmed/33590968
http://dx.doi.org/10.15252/msb.202010188
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