S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..
SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found that during SARS-CoV-2 infection, spike becomes lipid modified, through the sequential action of the S-acyltransferases ZDHHC20 and 9. Particularly striking is the rapid acylation of spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics, and biochemical approaches, we show that this massive lipidation controls spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid-rich lipid nanodomains in the early Golgi, where viral budding occurs. Finally, S-acylation of spike allows the formation of viruses with enhanced fusion capacity. Our study points toward S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets.
| Errataetall: |
CommentIn: Dev Cell. 2021 Oct 25;56(20):2787-2789. - PMID 34699787 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
Developmental cell - 56(2021), 20 vom: 25. Okt., Seite 2790-2807.e8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mesquita, Francisco S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.11.2021 Date Revised 21.12.2022 published: Print-Electronic CommentIn: Dev Cell. 2021 Oct 25;56(20):2787-2789. - PMID 34699787 Citation Status MEDLINE |
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| doi: |
10.1016/j.devcel.2021.09.016 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331411881 |
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| 500 | |a CommentIn: Dev Cell. 2021 Oct 25;56(20):2787-2789. - PMID 34699787 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found that during SARS-CoV-2 infection, spike becomes lipid modified, through the sequential action of the S-acyltransferases ZDHHC20 and 9. Particularly striking is the rapid acylation of spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics, and biochemical approaches, we show that this massive lipidation controls spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid-rich lipid nanodomains in the early Golgi, where viral budding occurs. Finally, S-acylation of spike allows the formation of viruses with enhanced fusion capacity. Our study points toward S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets | ||
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| 650 | 4 | |a S-palmitoylation | |
| 650 | 4 | |a SARS | |
| 650 | 4 | |a ZDHHC | |
| 650 | 4 | |a coronavirus | |
| 650 | 4 | |a lipid microdomains | |
| 650 | 4 | |a lipid sorting | |
| 650 | 4 | |a spike | |
| 650 | 4 | |a viral envelope | |
| 650 | 4 | |a virus | |
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| 700 | 1 | |a Sergeeva, Oksana |e verfasserin |4 aut | |
| 700 | 1 | |a Turelli, Priscilla |e verfasserin |4 aut | |
| 700 | 1 | |a Qing, Enya |e verfasserin |4 aut | |
| 700 | 1 | |a Kunz, Béatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Raclot, Charlène |e verfasserin |4 aut | |
| 700 | 1 | |a Paz Montoya, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Abriata, Luciano A |e verfasserin |4 aut | |
| 700 | 1 | |a Gallagher, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Dal Peraro, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Trono, Didier |e verfasserin |4 aut | |
| 700 | 1 | |a D'Angelo, Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a van der Goot, F Gisou |e verfasserin |4 aut | |
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