ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection
Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.
| Errataetall: |
UpdateIn: PLoS Biol. 2022 Sep 13;20(9):e3001754. - PMID 36099266 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2021 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2021) vom: 23. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ching, Krystal L [VerfasserIn] |
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Date Revised 13.10.2022 published: Electronic UpdateIn: PLoS Biol. 2022 Sep 13;20(9):e3001754. - PMID 36099266 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2021.12.17.473223 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM335165028 |
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| 500 | |a UpdateIn: PLoS Biol. 2022 Sep 13;20(9):e3001754. - PMID 36099266 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection | ||
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| 700 | 1 | |a Gago, Juan |e verfasserin |4 aut | |
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| 700 | 1 | |a Liang, Feng-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Thorpe, Lorna E |e verfasserin |4 aut | |
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| 700 | 1 | |a Segal, Leopoldo N |e verfasserin |4 aut | |
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| 700 | 1 | |a Torres, Victor J |e verfasserin |4 aut | |
| 700 | 1 | |a Cadwell, Ken |e verfasserin |4 aut | |
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