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1.
J Extracell Vesicles ; 10(8): e12112, 2021 06.
Article in English | MEDLINE | ID: covidwho-1272198

ABSTRACT

In late 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. SARS-CoV-2 and the disease it causes, coronavirus disease 2019 (COVID-19), spread rapidly and became a global pandemic in early 2020. SARS-CoV-2 spike protein is responsible for viral entry and binds to angiotensin converting enzyme 2 (ACE2) on host cells, making it a major target of the immune system - particularly neutralizing antibodies (nAbs) that are induced by infection or vaccines. Extracellular vesicles (EVs) are small membraned particles constitutively released by cells, including virally-infected cells. EVs and viruses enclosed within lipid membranes share some characteristics: they are small, sub-micron particles and they overlap in cellular biogenesis and egress routes. Given their shared characteristics, we hypothesized that EVs released from spike-expressing cells could carry spike and serve as decoys for anti-spike nAbs, promoting viral infection. Here, using mass spectrometry and nanoscale flow cytometry (NFC) approaches, we demonstrate that SARS-CoV-2 spike protein can be incorporated into EVs. Furthermore, we show that spike-carrying EVs act as decoy targets for convalescent patient serum-derived nAbs, reducing their effectiveness in blocking viral entry. These findings have important implications for the pathogenesis of SARS-CoV-2 infection in vivo and highlight the complex interplay between viruses, extracellular vesicles, and the immune system that occurs during viral infections.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/therapy , Extracellular Vesicles/chemistry , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/immunology , COVID-19/virology , Flow Cytometry , HEK293 Cells , Humans , Immunization, Passive , Protein Binding , Spike Glycoprotein, Coronavirus/analysis
2.
Circ Res ; 128(8): 1214-1236, 2021 04 16.
Article in English | MEDLINE | ID: covidwho-1186415

ABSTRACT

A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Cardiovascular Diseases/virology , Myocytes, Cardiac/virology , SARS-CoV-2/physiology , Virus Internalization , Biomarkers/metabolism , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Cardiomyopathies/virology , Gene Expression , Humans , Immune System/physiology , Myocardium/enzymology , Myocytes, Cardiac/enzymology , Neuropilin-1/metabolism , Platelet Activation , RNA, Messenger/metabolism , Renin-Angiotensin System/physiology , Return to Sport , Risk Factors , SARS-CoV-2/ultrastructure , Spike Glycoprotein, Coronavirus/metabolism , Troponin/metabolism , Ventricular Remodeling , Virus Attachment , Virus Internalization/drug effects
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