The D614G Mutation Enhances the Lysosomal Trafficking of SARS-CoV-2 Spike
The spike D614G mutation increases SARS-CoV-2 infectivity, viral load, and transmission but the molecular mechanism underlying these effects remains unclear. We report here that spike is trafficked to lysosomes and that the D614G mutation enhances the lysosomal sorting of spike and the lysosomal accumulation of spike-positive punctae in SARS-CoV-2-infected cells. Spike trafficking to lysosomes is an endocytosis-independent, V-ATPase-dependent process, and spike-containing lysosomes drive lysosome clustering but display poor lysotracker labeling and reduced uptake of endocytosed materials. These results are consistent with a lysosomal pathway of coronavirus biogenesis and raise the possibility that a common mechanism may underly the D614G mutation's effects on spike protein trafficking in infected cells and the accelerated entry of SARS-CoV-2 into uninfected cells.
| Errataetall: |
UpdateIn: Sci Adv. 2022 Dec 23;8(51):eade5085. - PMID 36563151 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 09. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Chenxu [VerfasserIn] |
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Date Revised 15.06.2023 published: Electronic UpdateIn: Sci Adv. 2022 Dec 23;8(51):eade5085. - PMID 36563151 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.12.08.417022 |
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NLM318959186 |
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| 520 | |a The spike D614G mutation increases SARS-CoV-2 infectivity, viral load, and transmission but the molecular mechanism underlying these effects remains unclear. We report here that spike is trafficked to lysosomes and that the D614G mutation enhances the lysosomal sorting of spike and the lysosomal accumulation of spike-positive punctae in SARS-CoV-2-infected cells. Spike trafficking to lysosomes is an endocytosis-independent, V-ATPase-dependent process, and spike-containing lysosomes drive lysosome clustering but display poor lysotracker labeling and reduced uptake of endocytosed materials. These results are consistent with a lysosomal pathway of coronavirus biogenesis and raise the possibility that a common mechanism may underly the D614G mutation's effects on spike protein trafficking in infected cells and the accelerated entry of SARS-CoV-2 into uninfected cells | ||
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| 700 | 1 | |a Li, Maggie |e verfasserin |4 aut | |
| 700 | 1 | |a Pekosz, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Atai, Nadia |e verfasserin |4 aut | |
| 700 | 1 | |a Gould, Stephen J |e verfasserin |4 aut | |
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