Defensosomes Serve as Decoys to Inhibit SARS-CoV-2 Infection
- Description
Exosomes mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Recently, a subset of exosomes was labeled as defensosomes that are assembled during bacterial infection. Defensosomes mediate host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens through incorporating protein receptors on their surface. Therefore, this study examined the role of defensosomes during infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the etiological agent of Coronavirus Disease 2019 (COVID-19). It was found that ACE2+ exosomes were induced by SARS-CoV-2 infection, which are defined as defensosomes. This study showed that ACE2+ defensosomes directly bind and block viral entry.
This dataset includes raw sequencing data, as well as supplementary data tied to the publication. The supplementary data contains data about characteristics of exosomes from COVID-19 patient bronchoalveolar lavage fluid, characterizing role of exosomes against SARS-CoV-2 in vitro, cryo-EM tomogram and 3D rendering of an exosome and SARS-CoV-2 virion, low expression of the short ACE2 isoform dACE2 detected in a subset of COVID patients, correlation of dACE2 expression in COVID patients with various interferon stimulated genes, full-length ACE2 and not dACE2 is loaded onto exosomes, heatmap of IPA analysis including comparisons between “high” and “low” groups for percent ACE2+ exosomes and ACE2 mean fluorescence intensity (MFI) value, and signaling pathway analysis of differentially expressed genes in the “high” percent ACE2+ exosome group and differentially expressed genes in the “high” ACE2 MFI exosome group.
The supplementary data also contains video about tomograms from Cryo-ET of SARS-CoV-2 and ACE2+ exosomes, low expression of the short ACE2 isoform dACE2 detected in a subset of COVID patients, and tomographic reconstructions of exosomes and virions. The data even includes raw western blot images and tables that contain data about demographics and clinical characteristics of the COVID-19 patient cohort, regression using negative binomial model and length of stay in the intensive care unit (ICU) as the outcome, linear regression on covariates including ACE2 MFI using length of stay in the ICU as the outcome and ACE2 MFI using ventilation days as an outcome, and regression using negative binomial model and ventilation days as the outcome. The data indicate that defensosomes may contribute to the antiviral response against SARS-CoV-2.
Access
- Restrictions
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Free to All
- Instructions
- Data and supporting files are available on PubMed Central (PMC) under Supplementary Materials. Raw sequencing data have been deposited in the Sequence Read Archive (SRA) and can be accessed through BioProject.
- Grant Support
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HHMI Faculty Scholars/Howard Hughes Medical InstituteNSF Graduate Research Fellowship/National Science FoundationCrohn’s & Colitis Foundation/Crohn’s & Colitis FoundationKenneth Rainin Foundation/Kenneth Rainin FoundationJudith & Stewart Colton Center for Autoimmunity/NYU Langone HealthCOVID-19 Seed Research Fund/NYU Grossman School of MedicineAntimicrobial-Resistant Pathogens Program/NYU Langone Health