In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 9 ( 2022-9-13), p. e3001754-
Abstract:
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 Coronavirus Disease 2019 (COVID-19). Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchoalveolar lavage fluid (BALF) from critically ill COVID-19 patients was associated with reduced intensive care unit (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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001754
DOI:
10.1371/journal.pbio.3001754.g001
DOI:
10.1371/journal.pbio.3001754.g002
DOI:
10.1371/journal.pbio.3001754.g003
DOI:
10.1371/journal.pbio.3001754.g004
DOI:
10.1371/journal.pbio.3001754.t001
DOI:
10.1371/journal.pbio.3001754.s001
DOI:
10.1371/journal.pbio.3001754.s002
DOI:
10.1371/journal.pbio.3001754.s003
DOI:
10.1371/journal.pbio.3001754.s004
DOI:
10.1371/journal.pbio.3001754.s005
DOI:
10.1371/journal.pbio.3001754.s006
DOI:
10.1371/journal.pbio.3001754.s007
DOI:
10.1371/journal.pbio.3001754.s008
DOI:
10.1371/journal.pbio.3001754.s009
DOI:
10.1371/journal.pbio.3001754.s010
DOI:
10.1371/journal.pbio.3001754.s011
DOI:
10.1371/journal.pbio.3001754.s012
DOI:
10.1371/journal.pbio.3001754.s013
DOI:
10.1371/journal.pbio.3001754.s014
DOI:
10.1371/journal.pbio.3001754.s015
DOI:
10.1371/journal.pbio.3001754.s016
DOI:
10.1371/journal.pbio.3001754.s017
DOI:
10.1371/journal.pbio.3001754.s018
DOI:
10.1371/journal.pbio.3001754.s019
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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