Proteomic analysis identifies the RNA helicase DDX3X as a host target against SARS-CoV-2 infection
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved..
COVID-19 is currently a highly pressing health threat and therapeutic strategies to mitigate the infection impact are urgently needed. Characterization of the SARS-CoV-2 interactome in infected cells may represent a powerful tool to identify cellular proteins hijacked by viruses for their life cycle and develop host-oriented antiviral therapeutics. Here we report the proteomic characterization of host proteins interacting with SARS-CoV-2 Nucleoprotein in infected Vero E6 cells. We identified 24 high-confidence proteins mainly playing a role in RNA metabolism and translation, including RNA helicases and scaffold proteins involved in the formation of stress granules, cytoplasmic aggregates of messenger ribonucleoproteins that accumulate as a result of stress-induced translation arrest. Analysis of stress granules upon SARS-CoV-2 infection showed that these structures are not induced in infected cells, neither eIF2α phosphorylation, an upstream event leading to stress-induced translation inhibition. Notably, we found that G3BP1, a stress granule component that associates with the Nucleoprotein, is required for efficient SARS-CoV-2 replication. Moreover, we showed that the Nucleoprotein-interacting RNA helicase DDX3X colocalizes with viral RNA foci and its inhibition by small molecules or small interfering RNAs significantly reduces viral replication. Altogether, these results indicate that SARS-CoV-2 subverts the stress granule machinery and exploits G3BP1 and DDX3X for its replication cycle, offering groundwork for future development of host-directed therapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:190 |
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| Enthalten in: |
Antiviral research - 190(2021) vom: 30. Juni, Seite 105064 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ciccosanti, Fabiola [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.07.2021 Date Revised 17.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2021.105064 |
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NLM323376134 |
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| 245 | 1 | 0 | |a Proteomic analysis identifies the RNA helicase DDX3X as a host target against SARS-CoV-2 infection |
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| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a COVID-19 is currently a highly pressing health threat and therapeutic strategies to mitigate the infection impact are urgently needed. Characterization of the SARS-CoV-2 interactome in infected cells may represent a powerful tool to identify cellular proteins hijacked by viruses for their life cycle and develop host-oriented antiviral therapeutics. Here we report the proteomic characterization of host proteins interacting with SARS-CoV-2 Nucleoprotein in infected Vero E6 cells. We identified 24 high-confidence proteins mainly playing a role in RNA metabolism and translation, including RNA helicases and scaffold proteins involved in the formation of stress granules, cytoplasmic aggregates of messenger ribonucleoproteins that accumulate as a result of stress-induced translation arrest. Analysis of stress granules upon SARS-CoV-2 infection showed that these structures are not induced in infected cells, neither eIF2α phosphorylation, an upstream event leading to stress-induced translation inhibition. Notably, we found that G3BP1, a stress granule component that associates with the Nucleoprotein, is required for efficient SARS-CoV-2 replication. Moreover, we showed that the Nucleoprotein-interacting RNA helicase DDX3X colocalizes with viral RNA foci and its inhibition by small molecules or small interfering RNAs significantly reduces viral replication. Altogether, these results indicate that SARS-CoV-2 subverts the stress granule machinery and exploits G3BP1 and DDX3X for its replication cycle, offering groundwork for future development of host-directed therapies | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Colavita, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Refolo, Giulia |e verfasserin |4 aut | |
| 700 | 1 | |a Castilletti, Concetta |e verfasserin |4 aut | |
| 700 | 1 | |a Agrati, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Brai, Annalaura |e verfasserin |4 aut | |
| 700 | 1 | |a Manetti, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Botta, Lorenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Capobianchi, Maria Rosaria |e verfasserin |4 aut | |
| 700 | 1 | |a Ippolito, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Piacentini, Mauro |e verfasserin |4 aut | |
| 700 | 1 | |a Fimia, Gian Maria |e verfasserin |4 aut | |
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